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  UNITED STATES OF AMERICA DEPARTMENT OF
         HEALTH AND HUMAN SERVICES
        FOOD AND DRUG ADMINISTRATION

                   + + + + +

               PUBLIC WORKSHOP

                   + + + + +

  PHASE OUT OF CFC-PROPELLED EPINEPHRINE
             INHALATION AEROSOL

                   + + + + +

         FRIDAY, SEPTEMBER 25, 2009

                   + + + + +

      The workshop convened at 8:30 a.m. in
room 1066, 5630 Fishers Lane, Rockville,
Maryland. Sally Seymour, Chair, presiding.




Reporter: Eric Hendrixson




               Neal R. Gross & Co., Inc.
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FDA PANEL MEMBERS PRESENT:

SALLY SEYMOUR, MD, Deputy Director, Division
      of Pulmonary & Allergy Products
BADRUL CHOWDHURY, MD, PhD, Director, Division
      of Pulmonary & Allergy Products
MARTHA NGUYEN, JD, Office of Regulatory
      Policy
ELLEN FRANK, Director, Division of Public
      Affairs
ANDREA LEONARD-SEGAL, MD, Director, Division
      of Nonprescription Evaluation

ALSO PRESENT:

LESLIE HENDELES, PharmD, University of
      Florida
RUTH PARKER, MD, Emory University
MARCUS REIDENBERG, MD, Weill Cornell Medical
      College
DIANA SCHMIDT, National Heart, Lung & Blood
      Institute
MARK LIU, MD, Johns Hopkins University
STEPHEN CAMPBELL, ESQ., Amphastar
      Pharmaceuticals
ROSS BRENNAN, Environmental Protection Agency




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             TABLE OF CONTENTS

ITEM                                       PAGE

Welcome....................................4

Introduction/Background....................6

Asthma, Epinephrine & Therapeutic.........33
 Alternatives

Perspective on the........................75
 Under-Served Population

Epinephrine Use & Communication Plan.....112

Communication Challenges.................135

Educating the Public.....................166

Open Public Session......................192

Roundtable Discussion....................225

Adjourn




               Neal R. Gross & Co., Inc.
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 1                  P-R-O-C-E-E-D-I-N-G-S

 2                                                     8:38 a.m.

 3                  CHAIR SEYMOUR: Good morning.             I

 4   think we're going to go ahead and get started.

 5    I want to welcome everybody to the FDA Public

 6   Workshop today, on educating the public about

 7   the removal of essential use designation for

 8   epinephrine, and before we begin our day's

 9   presentations,       we'd   like    to    start      with

10   introductions today of the FDA panel and the

11   speakers that are sitting up here.

12                  So, I'll start with myself.            My

13   name    is   Sally    Seymour    and     I'm   the    Deputy

14   Director     for   Safety   in     the    Division     of

15   Pulmonary and Allergy Products, and welcome.

16                  DR. PARKER: I'm Ruth Parker, Emory

17   University School of Medicine.

18                  DR.      REIDENBERG:         I'm       Marcus

19   Reidenberg, Internist and Pharmacologist at

20   Weill    Cornell     Medical    College     in New York

21   City.

22                  DR. HENDELES: I'm Leslie Hendeles.




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 1    I'm a clinical pharmacist in the Pulmonary

 2   Division at the University of Florida.

 3                DR.         CHOWDHURY:         I'm       Badrul

 4   Chowdhury.        I'm    the   Division       Director,

 5   Division of Pulmonary and Allergy Products.

 6                DR.        LEONARD-SEGAL:         I'm     Andrea

 7   Leonard-Segal.          I   direct    the     Division      of

 8   Nonprescription Clinical Evaluation at FDA.

 9                MS. FRANK: I'm Ellen Frank, the

10   Director of the Division of Public Affairs in

11   the Center for Drug Evaluation and Research at

12   FDA.

13                DR.    NGUYEN:      Martha     Nguyen,      I'm

14   Regulatory Council in the Office of Regulatory

15   Policy at FDA.

16                CHAIR      SEYMOUR:      We're    going     to

17   begin this morning's presentation with Dr.

18   Andrea Leonard-Segal and she's going to give

19   us a little bit of information about what the

20   purpose of this meeting is and what we hope to

21   gain out of the meeting today.

22                In    the      morning    session       will   be




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 1   primarily presentations and in the afternoon,

 2   we will have a roundtable discussion, when we

 3   bring some additional folks up to have some

 4   questions discussed, and we'll introduce them

 5   at that time.

 6                  So,    I'll    turn    it     over    to       Dr.

 7   Leonard-Segal.

 8                  DR.    LEONARD-SEGAL:         Great,      thank

 9   you, Sally.     Well, good morning, everybody.                  I

10   want to thank you all for coming today.                  We

11   think that this is a very important workshop,

12   because we are very concerned about informing

13   the   public    about    a    major    change       in    the

14   availability     of    chlorofluorocarbon           or    CFC-

15   propelled over-the-counter epinephrine metered

16   dose inhalers.

17                  We're having this workshop because

18   these   metered      dose    inhalers      are no longer

19   going to be available by the end of December

20   2011.     That's      two    years    from    now,       and

21   currently, there are no other over-the-counter

22   metered dose inhalers for asthma treatment.




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 1                  So, we need to educate the over-

 2   the-counter consumers about this phase out and

 3   to let them know that they're not going to be

 4   able to get this product in two years.

 5                  The problem is that we don't know

 6   who is using the product.           So, we don't know

 7   how best to educate the people that are using

 8   it.     We don't know what to tell them and we

 9   don't know how to disseminate the message,

10   hence, this workshop.

11                 By    way    of   a    little    history,

12   epinephrine    is    a    short     acting    adrenergic

13   bronchodilator and it's been over-the-counter

14   since the mid 1950s.        That's the OTC drug

15   facts terminology for the indication for this

16   product,    are    that    it   temporarily      relieves

17   shortness of breath, tightness of the chest

18   and wheezing due to bronchial asthma.             It also

19   eases    breathing    for    asthma     patients,    by

20   reducing spasms of bronchial muscles.

21                 The labeling says not to use the

22   product, unless a doctor has diagnosed asthma.




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 1                So, what are we going to do today?

 2    Well,   first,    you're   going   to    hear    Dr.

 3   Chowdhury   provide    information      about    FDA's

 4   requirements under the Montreal Protocol on

 5   Substances that Deplete the Ozone Layer and

 6   the Clean Air Act.

 7                These impact the availability of

 8   the over-the-counter epinephrine metered dose

 9   inhaler.

10               Then, FDA hopes to learn from our

11   speakers and from others who are going to

12   speak publically later in the afternoon.           We

13   hope to learn about the scope of use of the

14   CFC metered dose inhalers.

15               By the end of the day, we hope to

16   have come to some consensus about what the

17   primary message is to convey to the consumers

18   about the phase-out should be and the best way

19   to   disseminate    these   messages,    and     also,

20   hopefully, this workshop can actually serve as

21   our first educational step for the over-the-

22   counter consumer.     If people hear about this




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 1   workshop, we hope that this will start to

 2   alert them to the fact that changes will be

 3   coming.

 4                      So, the agenda for today, after

 5   I'm     done      speaking,      you'll    hear    from    Dr.

 6   Chowdhury about the Montreal Protocol.                   Then

 7   Dr. Hendeles from Florida will speak to us

 8   about       asthma        and     epinephrine       and      the

 9   therapeutic alternatives.             Then Dr. Reidenberg

10   from Cornell will talk to us about who is

11   using      this    product      and   provide      us    with    a

12   perspective on the under-served population.

13                     Then, we'll have a break.             After

14   the break, we'll hear from Stephen Campbell

15   from Amphastar, which is the maker of the CFC

16   epinephrine metered dose inhaler.                 He'll talk

17   to    us    about    the    epinephrine      use     and    the

18   company's communication plan, for the phase-

19   out.

20                     Then,    Dr.    Parker    from     Emory      is

21   going to talk to us about the communication

22   challenges that we face in getting the word




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 1   out about the phase-out.

 2                   Ellen Frank from FDA at              11:30

 3   a.m. will talk to us about what FDA's options

 4   are, what tools we have at our disposal for

 5   providing educational messages for the OTC

 6   consumer about this phase-out. Then we'll have

 7   lunch,    then     there     will     be    an     open    public

 8   session, a roundtable discussion and questions

 9   and answers.

10                   So,    I    thank    everyone       for    being

11   here.    We look forward to a very fruitful day

12   and hopefully, this workshop will speed us

13   along our path to providing the education that

14   we need to provide.

15                   CHAIR      SEYMOUR:      Thank     you,    Dr.

16   Leonard-Segal.          Before      we     begin    with     Dr.

17   Chowdhury's presentation, we had a couple of

18   other panelists join us up at the podium.                    So,

19   I'd    like   to   have      them    to     go   ahead     and

20   introduce themselves, please.               Thank you.

21                   DR. LIU: My name is Mark Liu.                I'm

22   from    Johns    Hopkins      and    just     here    as     an




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 1   advisor.

 2                  MR. BRENNAN: Good morning.                 I'm

 3   Ross Brennan with the Environmental Protection

 4   Agency.

 5                  DR.        CHOWDHURY:        Good      morning,

 6   everybody, and welcome.            I will be taking the

 7   next   20    minutes       or   so    and    make     some

 8   introductory comments on the background to the

 9   phase-out       of        CFC-propelled           epinephrine

10   inhalation aerosol in the U.S. and give you

11   some relevant history, what brought us to this

12   point, including going into the genesis and

13   background of the Montreal Protocol and how

14   that affects some U.S. laws and regulations,

15   specifically,       the    regulations        of    the    FDA,

16   under which we are phasing out this product,

17   and also, the Clean Air Act of the EPA, under

18   which the sole phase-out essentially operates.

19                  As    you    are      probably      aware     of,

20   earth's     atmosphere      high      up    has    ozone     and

21   depletion of that ozone layer is what is of

22   concern.




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 1                   On     the   left-hand      side       of    the

 2   picture    here,       you   see    the    earth       and    the

 3   altitudes of atmosphere around it and way up

 4   in the stratosphere is where the ozone layer

 5   lies.

 6                   The     ozone     higher    up    in     the

 7   stratosphere, which goes up very high in the

 8   altitude    is       where   it    is    necessary       and

 9   actually, is a good thing to have, because it

10   protects the ultraviolet-B light of the sun,

11   penetrating deeper down.

12                   The typical ozone warning that we

13   often hear of the ozone, which is in the low

14   area of the earth, close to the earth's crust,

15   and that ozone is a bad ozone.

16                   So, to make the distinction, the

17   ozone    we're talking about is high up in the

18   stratosphere, which is the good one, because

19   it protects the UV-B from the sun, coming to

20   the earth and causing negative consequence.

21                   On    the    right-hand      side      of    the

22   panel,    see    one    picture,        there    are    many




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 1   pictures like that.            The area in deep blue or

 2   purple,     over      the     Antarctic   is   a     picture

 3   showing the ozone hole, or the area where the

 4   ozone is depleted.            As you can see from the

 5   picture, it's a very large surface where the

 6   ozone is depleted           and this actually happens

 7   to be one of the worst case pictures taken,

 8   back in 2006, towards the end of the year in

 9   September.

10                   So, this is the problem and the

11   whole idea here is to protect the ozone layer

12   and protect the emission or limit the emission

13   substances that causes this depletion, with

14   the aim that the ozone will be replenished

15   over years to come.

16                   Now, the negative consequences of

17   this   higher      up    in    the   stratosphere      ozone

18   depletions are many.           Some of the one them are

19   listed     in   the     slide     here,   in   the    second

20   bullet.     Examples include, skin cancers, both

21   of   the    melanoma        and   non-melanoma     kind,

22   cataract, immune status changes, as well as




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 1   many   other         negative        effects      on     the

 2   environment,      such       as    damage    to   plants,

 3   plankton        in    the     ocean's      photic    zone     and

 4   others.

 5                   So,    what       we're    concerned     about

 6   because of the ozone depletion is negative

 7   held consequence, among others.               What we're

 8   trying to achieve here in larger scale is to

 9   protect the ozone layer, to overcome                 these

10   negative consequences.

11                On this slide, and the subsequent

12   four slides, I will walk you through very

13   briefly,   on    the     history      of    the     Montreal

14   Protocol, under which these ozone depleting

15   substances, regulations or policies globally

16   fall under and also, at the same time, explain

17   to you, what are the U.S. obligations and what

18   are the U.S. laws and regulations under the

19   Montreal Protocol.

20                The       two    of    them    which      I'll    be

21   quoting multiple times, are the CAA, or the

22   Clean Air Act of the EPA and the U.S. FDA's




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 1   regulation, 21 CFR 2.125, which are the two

 2   regulations under which these ozone depleting

 3   substances are essentially regulated in the

 4   U.S., and this falls under the global Montreal

 5   Protocol principles.

 6                The whole thing started back in

 7   1974, when two scientists, at that time at

 8   University of California, Irvine, was working

 9   on stratospheric ozone and showed at that time

10   that chlorine from degraded CFCs were reaching

11   up to the stratosphere and causing depletion

12   of the ozone layer.    The article was published

13   in Nature back in 1974, and subsequently for

14   that work, these two investigators won the

15   Nobel Prize for chemistry.

16                At that time, the use of CFCs were

17   widespread, essentially in lot of places in

18   the   consumer   industry,   for   example,   in

19   refrigeration, air conditioners and many other

20   products, including the medical products that

21   we're talking about today.

22                The time line when it started was




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 1   1974.           Very    soon      after     that,    it    was

 2   approximately four years later, in 1978, in

 3   response       to    this    finding,       the    CFC    was

 4   considered to be harmful for the environment

 5   and     the    U.S.    actually      took     initiative        in

 6   planning to ban the use of these products,

 7   specifically the Clean Air Act and the CFR

 8   2.125 started at that time, with the goal of

 9   reducing the use of CFCs, essentially coming

10   down to zero, and earlier the ban was in

11   consumer products.

12                   This        is     remarkable       given        a

13   scientific publication in 1974 and the U.S.

14   taking initiative and having some laws made

15   around it within three to four years.

16                   Approximately         nine    years       after

17   that,    the    Montreal         Protocol    was    formed.

18   Initially, there were 27 countries, including

19   the U.S. and the aim of the Montreal Protocol

20   was ultimately to eliminate the substances

21   that deplete the ozone layer.

22                   As      of       today,     virtually        all




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 1   countries of the world are signatories.              It's

 2   the    largest     international    body    with     the

 3   largest    countries      participating     in     that,

 4   larger    than     the   U.N.   itself,    and     it   is

 5   regarded as a model for success of global

 6   environmental treaties.

 7                 Over       the    year,     the      Montreal

 8   Protocol take on responsibilities to reduce or

 9   eliminate the production of essentially all

10   ozone depleting substances, going beyond CFCs,

11   including halons, HCFCs, methyl bromide and

12   other chemicals.

13                 As    I    said   before,    there    are

14   essentially two regulations that are really

15   under the Montreal Protocols and principle

16   scientific umbrella.        These are the Clean Air

17   Act,     which was codified in the U.S. law and

18   the FDA's CFR 2.125, and the Clean Air Act

19   governs all ozone depleting substances and the

20   FDA regulation 2.125 is specifically for the

21   medical products, which I'll be expanding on,

22   as I go ahead with my talk later.




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 1                  Now, under the Montreal Protocol,

 2   the idea here is to eliminate the use of CFCs

 3   and I'm quoting here, one decision of the

 4   Montreal     Protocol      that    essentially        is     the

 5   governing scientific principle, if you would

 6   call it, and the decision is called 4/25, just

 7   to orient you four, means the fourth meeting

 8   of the parties, the meetings are held every

 9   year, and the 25 is a decision reached at that

10   party.

11                 So, here, essentially, there is a

12   scientific,       sort     of,      valid      principle

13   definition    of    what    is     essential      use,      and

14   that's what we're talking about here, removing

15   an essential use. So, essential use is defined

16   per   Montreal     Protocol,       as   use    that     is

17   necessary    for    the    health,      safety     or      is

18   critical    for    the    functioning       of    society,

19   encompassing both cultural and intellectual

20   aspects,     and     there        are    no      available

21   technically        and      economically           feasible

22   alternatives       or     substitutes         that      are




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 1   acceptable from the standpoint of environment

 2    and health.

 3                      It's a pretty high standard and

 4   the idea here is to have the high standard

 5   with the aim of ultimately eliminating all

 6   uses of CFCs.

 7                      Now, under the Montreal Protocol,

 8   the    use    of     CFCs   was      banned    in    developed

 9   countries, effective January 1996.                  So, it

10   actually has been banned long time ago, except

11   for essential use,          and it will be banned for

12   rest of the world in 2010.

13                   So,      what   it    really    means,       that

14   from   1996,       the    use   of    CFCs    in    developed

15   countries were banned.            The CFCs that we were

16   getting      for    essential      use,   such      as   in

17   inhalation aerosols, was under an exemption

18   process, which was every year, every year,

19   negotiation with the Montreal Protocol.                  So,

20   that's the way it was operating.

21                   For the rest of the world, other

22   countries, starting next year 2010, it will be




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 1   banned.       The       developing       countries      will

 2   actually be getting CFCs under the essential

 3   uses process.

 4   So,    the   year       2010    is   a    transition         year,

 5   essentially for the whole world, when the CFC

 6   use is going to stop.

 7                  Now, the use of CFCs in inhalation

 8   aerosols for asthma and COPD was and is, an

 9   exempted essential medical use.                  So, that was

10   essential use, which was defined and under

11   which we were operating as of now.

12                  Now,      one    thing      to    put    in    the

13   context      that       other    countries        developed,

14   essentially has moved out of using CFCs.

15   Of the developed countries, U.S. happens to be

16   the only one requesting for CFCs, and have

17   requested CFC use for 2010                and 11.      So,

18   standing out as one of the countries which is

19   sort   of,    in    a    global      sense,      amongst      the

20   developed countries, slowing in some way, in

21   the phase-out.       But we're getting there.

22                  This       is     a       chart     essentially




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 1   showing how this has translated to the use of

 2   CFCs globally and this particular chart is for

 3   developed countries only, the U.S., European,

 4   Japan,   Canada,    Switzerland    and   other

 5   countries.

 6                On the top two, the blue and the

 7   one below that, which is pinkish, you see the

 8   amount of CFCs nominated for use, which was

 9   allowed for use, that's the blue graph, and if

10   you can look at the left, when the process

11   started back in 1996, it was close to 13,000

12   metric ton, and if you walk down on the slide,

13   in the horizontal   axis and go to 2009, it's

14   coming down to essentially zero.   So, it's a

15   huge success.

16                The last two lines here, yellow

17   and the blue, is that for the U.S.   Again,

18   U.S. was using approximately 4,000 when the

19   whole thing started, 4,000 metric tons, and

20   now, U.S. is down to less than 100 metric ton.

21   So, the point here is a big success, which

22   this Montreal Protocol had in eliminating the




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 1   use of CFCs, and the point here is to get to

 2   zero, which is almost there.

 3                    Now, let me just move over and

 4   transition        into       getting     more     to      the

 5   epinephrine issue and as I get to it, I'll

 6   talk globally, how the regulatory process for

 7   removal     of    CFCs      in   the   United    States      has

 8   worked.

 9   As I stated before, it is codified in the CFR

10   which I quoted earlier, and the process for

11   the FDA for protecting public health is pretty

12   onerous and it should be and it was               and it

13   is.

14                    We   are    required    to     first   go

15   through advisory committee process, which is

16   open public meeting, published proposed rule,

17   have an open public meeting on the proposed

18   rule and then, publish final rule.               It's a

19   slow, deliberate process, with involvement of

20   all the parties and for the products which

21   have been eliminated for CFCs in the U.S.,

22   which are    the last subsequent slides, and for




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 1   epinephrine,   we    have    gone    through    this

 2   process.

 3               Now, let me talk about some other

 4   rules, how it happened and what happened and

 5   how we succeeded, so that one can actually

 6   have some idea of how it probably may impact

 7   the epinephrine phase-out.

 8               The     one   which     has   pretty     large

 9   public health impact is albuterol.           As we

10   know, albuterol inhalation aerosols are a very

11   commonly used drug, and in fact, in the U.S.,

12   it is pretty commonly used, and albuterol was

13   phased out, effective December 31, 2008, just

14   less than a year ago.       So, we phased that out.

15   The removal designation was justified by the

16   criteria which is in the second bullet, which

17   is again, qualified in the CFR language.             The

18   criteria for removal of albuterol included

19   availability of alternate products, adequate

20   supply of the alternate, adequate U.S. post-

21   marketing   history       and     patients     being

22   adequately served.




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 1   It    was   done    because     there   are   multiple

 2   products out there and effective December 31,

 3   2008, CFC-propelled albuterol is not in the

 4   market in the U.S. anymore.

 5                  As    I   said    before,   that   was    a

 6   pretty, I think, large task force, because

 7   approximately 50+ million prescriptions were

 8   dispensed for albuterol yearly at the time,

 9   and   it    was    the   seventh    most   commonly

10   prescribed medication, and the alternate that

11   was there was an adequate replacement product,

12   and some characteristics of differences are

13   listed in the slide.       I won't go into details,

14   because it's not relevant here.

15                 The point I want to make here is,

16   a related product, which is albuterol, was

17   successfully removed from the U.S. market just

18   last year.    Although there's difference, and

19   that's going to be here, albuterol was and is,

20   a prescription medication, whereas epinephrine

21   inhalation aerosol is not.

22                 Now, effective January 2005, which




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 1   is sort of more recent, if would call it, the

 2   U.S. published criteria for removal of CFC-

 3   propelled products.       So, this was put into

 4   place, again, through the public process and

 5   codified in to the U.S. law that what were the

 6   criteria that the U.S. will use for removal of

 7   other products, effective January 1, 2005.

 8   In principle, these criteria were to sort of

 9   match   the   idea   of    the   principle   of   the

10   Montreal Protocol's position 4/25, which I

11   quoted earlier.

12                 So, as of January 2005, as of now,

13   the criteria that we follow for removal of

14   essentiality are listed in the second bullet.

15   The three criteria, and satisfying one of

16   them is adequate.

17   These are, no technical barrier       exists to

18   reformulation, second, the product will not

19   provide an unavailable important public health

20   benefit, third, use of the product releases

21   cumulatively significant amount of CFCs in to

22   the atmosphere.




                       Neal R. Gross & Co., Inc.
                              202-234-4433
                                                                        Page 26
 1   Third one essentially means any release of CFC

 2   is   important.        It's    not     that      I'm       tiny,

 3   therefore, I'm okay, because it is cumulative.

 4               So, meeting any of these criteria

 5   are adequate for removal of essentiality of

 6   products,   effective      January       1,    2005,       and

 7   again, this is in the U.S. law and this has

 8   gone through the usual rule making process,

 9   and one point to note, that this allows for

10   removal of products for which there are no

11   alternates with the same active moiety.

12                So,    again,      this    is     the    way    we

13   operated.   These are done.          These are laws and

14   we are following these principles.

15   If we talk about some other molecules.                We

16   spoke about albuterol, that actually has been

17   phased   out,   and    this     slide    lists       some

18   products,       such          as       beclomethasone,

19   dexamethasone,        fluticasone,            bitolterol,

20   salmeterol, ergotamine, ipratropium, and these

21   essentiality of CFC use for these products

22   were removed, effective April 2007.




                        Neal R. Gross & Co., Inc.
                               202-234-4433
                                                                     Page 27
 1   This was relatively an easier rule because

 2   these products at that time, were actually not

 3   marketed.

 4                  There's      another     proposed       rule,

 5   which I'm just listing here for the sake of

 6   completion and to be very clear, this proposed

 7   rule is not a matter of discussion at this

 8   meeting.

 9   There are molecules which are listed here,

10   these    are   fluticasone,      triamcinolone         and

11   others, which you can read in the list.

12   There's    a   proposed     rule   to    remove     the

13   essentiality of these products and the date

14   proposed is on the slide here.

15                  This is a rule which is, as of

16   today, proposed, and it is under active agency

17   consideration,      and    the   removal     of    these

18   essentiality     is    justified      because     of    the

19   criteria    which     I   listed   earlier, which is

20   again,    quoted    here,    which     is   in    the    last

21   bullet, that there is no technical barrier to

22   reformulation, it does not provide otherwise




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                        Page 28
 1   important     public       health       benefit      and    the

 2   release of CFCs is cumulatively significant.

 3   So, with that, let me move on to my last three

 4   slides, and close it up, talking a bit about

 5   epinephrine.

 6                   The        CFC-propelled             epinephrine

 7   inhalation      aerosol      has     gone      through      the

 8   process    which      I    described       earlier,        the

 9   advisory    committee,           proposed      rule,    public

10   meeting, final rule, it has gone through all

11   of these processes.          It's done.        It is a final

12   rule.

13                 The rule basically says that the

14   CFC   essentiality         for    use    for    producing

15   epinephrine     inhalation         aerosol      is     removed,

16   effective December 31, 2011.              So, we have

17   approximately a year, two years to go, until

18   the   product    is       removed,      but    it    has    been

19   decided, it is final, that effective December

20   2011,   there    will       be      no    CFC-propelled

21   epinephrine inhalation aerosol.

22                 Again, the same criteria which I




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
                                                                 Page 29
 1   have talked so far twice, are listed here,

 2   that how it was justified, again, the three

 3   things, no barrier of formulation, does not

 4   provide otherwise unavailable public health

 5   benefit   and    the   release    is   cumulatively

 6   significant,     and   again,    recall,    these     are

 7   listed as criteria with the joining of an

 8   `and', which means removal is justified if one

 9   criteria,    not   all   three,    only    one   is

10   satisfied.

11                Epinephrine was done.         It has gone

12   through the rule making process and effective

13   2011, there will be no epinephrine inhalation

14   aerosol in the U.S. propelled by CFC.

15                Now, to go back to and link it to

16   the EPA's Clean Air Act and what does it

17   really mean practically, so that we are all on

18   the same page.

19                Section 610(e) of the Clean Air

20   Act specifically excludes medical devices that

21   meet the definition of essentiality, which

22   really meant for the FDA, to keep on having




                        Neal R. Gross & Co., Inc.
                               202-234-4433
                                                                             Page 30
 1   CFCs for the products, which are once under

 2   proposed rule, or even epinephrine now, that

 3   makes them essential, we have these products

 4   as products which are medically essential.

 5                   EPA's regulation of this ban, when

 6   it takes effect, which will be December 31,

 7   2011,    will    essentially         mean     no      sale    or

 8   distribution,          no     offer        for     sale       or

 9   distribution and cannot be put in interstate

10   commerce.

11   So, let me expand on these two, so that we're

12   all understanding what it means and what will

13   happen   in     2011,       when   this     rule      goes     into

14   effect   and     the    product       is    removed.           I'll

15   expand a bit on the sale and distribution,

16   expand a bit on interstate commerce.

17                   So,    this     component        of    sale       and

18   distribution       or        offer     for       sale        as

19   distribution, is not just retail sales.                      It

20   includes give-away, donation or any change of

21   ownership, which literally means, it will not

22   be there in the pharmacy stores.                 One cannot




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
                                                             Page 31
 1   give it in the hospitals, one cannot get it as

 2   a sample or donation.

 3   If patients have them for their personal use,

 4   they can use it, but they cannot get anymore.

 5                The          interstate        commerce,

 6   therefore,   is    to    the   entire   distribution

 7   chain, including steps in manufacturing and

 8   from there, to the point of ultimate sale to

 9   the consumer, and also includes import of any

10   products for sale or distribution within the

11   U.S.

12   So, it really is an end date, which really

13   means an end date that translates into, nobody

14   can make it, import it, put it for sale and it

15   will not be on the market.       So, that's the end

16   date, and that's the reason really, why we are

17   trying to ramp up       educational activities from

18   now, because it's not that we can wait for

19   December 2011 to come, because that's the end

20   date.   So, transition is expected to happen

21   now, with the aim of the patients moved over

22   to alternate treatments.




                        Neal R. Gross & Co., Inc.
                               202-234-4433
                                                                    Page 32
 1                 So,    I'll     close    out    by    talking

 2   about some challenges and issues that we would

 3   like   you   to   discuss      and    Dr.    Segal      has

 4   mentioned this, on her presentation as well.

 5   One challenge is, given it is an OTC product,

 6   it's challenging to find out who the current

 7   users of these products are.           So, developing

 8   regulation    activity      requires     that      to    be

 9   achieved.

10                Second     is,    reaching      the     current

11   users, with the message that CFC epinephrine

12   aerosol will not be there, effective December

13   31, 2011.

14                So, the challenge is how to find

15   out who those people are and second is how to

16   get to those people and tell them that this

17   product that you are using now will not be

18   available come December 2011, and what is the

19   best way to transition these patients to the

20   right alternate treatment, which is important,

21   given epinephrine being an over-the-counter

22   drug and the rational, reasonable, commonly




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                        Page 33
 1   used inhalation short acting bronchodilator

 2   being albuterol is a prescription drug.

 3                     Overall, our aim to go through the

 4   transition safely and effectively, with the

 5   aim     of   protecting      the   public        health    of

 6   patients,      or    the    health    of     patients      who

 7   currently use these products.               Thank you very

 8   much.

 9                     CHAIR    SEYMOUR:       Thank    you,    Dr.

10   Chowdhury.     I think we have a few minutes, if

11   there are any clarifying questions for Dr.

12   Chowdhury, before we move to Dr. Hendeles.

13   I ask if you do have any questions, if you

14   come    up   to     the    microphone      and     introduce

15   yourself, before you ask your question.

16                  Okay, I think we can move onto Dr.

17   Hendeles next.

18                  DR.     HENDELES:      Good      morning,     and

19   thank    you   for     inviting      me    to     give    this

20   presentation. I        really applaud the FDA on

21   looking forward and addressing this issue so

22   far in advance, so that maybe we can prevent




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
                                                                 Page 34
 1   some patients from dying from asthma.

 2   I have four messages that I want to address.

 3   The first is that, what is asthma and how does

 4   it present differently, in different types of

 5   patients and what pathophysiologic features

 6   might determine whether a bronchodilator alone

 7    is sufficient.

 8                  I'll     discuss    the     bronchodilator

 9   response to epinephrine, in relationship to

10   albuterol, the need for corticosteroids, both

11   for   relieving    acute    symptoms       that are not

12   bronchodilator responsive and also, the use of

13   inhaled corticosteroids for preventing asthma

14   exacerbation and lastly, the lack of efficacy

15   of the nonprescription oral tablets that are

16   available and will still be available after

17   this action.

18                 So, the symptoms of asthma vary

19   within the same patient and between patients,

20   but basically, wheeze, cough, chest tightness

21   are   very   common,     both     during    an   acute

22   exacerbation      and     also,      chronically      and




                       Neal R. Gross & Co., Inc.
                              202-234-4433
                                                                       Page 35
 1   shortness of breath, particularly during times

 2   of acute exacerbation.

 3                   One    old    adage     that   I    remember

 4   being     taught    many     years    ago    was    that    all

 5   asthma does not wheeze and all wheeze is not

 6   asthma.

 7   So, that one of the important features of

 8   evaluating these patients is measuring lung

 9   function      and   using     that    as    part    of   both

10   diagnosis and guide to therapy.

11                  One of the limitations of over-

12   the-counter treatment, self-treatment, is that

13   the patient does not have the benefit of a

14   health care professional evaluating the type

15   of   asthma    they     have,    or   if     they   do     have

16   asthma.

17                  There       are    two       main    clinical

18   presentations.             The   intermittent       asthma

19   patient has extended periods where they're

20   free of symptoms.        It may be weeks or months

21   where they don't have any asthma symptoms.                  If

22   you measure their lung function when they're




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
                                                            Page 36
 1   asymptomatic,    their   pulmonary    function    is

 2   normal.

 3   But because they're intermittent doesn't mean

 4   that they're necessarily mild.       They could

 5   have intermittent attacks that could be life

 6   threatening.

 7               In    contrast,   the    patient   with

 8   persistent asthma is continuously symptomatic

 9   or frequently having recurring symptoms and by

10   definition from the National Asthma Education

11   Program, that would be twice a week or more,

12   where they would have symptoms and that would

13   be classified as persistent.

14              The strategy for treating patients

15   with intermittent asthma is different than it

16   is for persistent asthma.

17   In the case of intermittent asthma, the goal

18   is to relieve the symptoms when they occur,

19   and of course, the first line therapy is a

20   short acting beta agonist.

21              In contrast, with the persistent

22   asthma, the goal is to prevent the asthma




                      Neal R. Gross & Co., Inc.
                             202-234-4433
                                                               Page 37
 1   attack     and   because     of     the    underlying

 2   inflammation, as you'll see in a few minutes,

 3   inhaled corticosteroids are the cornerstone of

 4   preventing asthma symptoms in the patient with

 5   persistent asthma.

 6                 This if from the National Asthma

 7   Education and Prevention Program guidelines.

 8   The expert panel report was revised for the

 9   third time in 2007.     The important features

10   are that they divide patients based upon the

11   frequency of symptoms, the intermittent versus

12   the persistent and some of the features of

13   what distinguishes between the three types of

14   persistent asthma is how often they're having

15   symptoms, whether they're waking up at night

16   coughing or wheezing and how often they're

17   using a short acting beta agonist.

18   So,   if   they're   using   a    short   acting   beta

19   agonist more than twice a week, they would

20   have persistent asthma, and if they were using

21   it daily, and that's not uncommon, by the way,

22   for patients who are not being treated with




                      Neal R. Gross & Co., Inc.
                             202-234-4433
                                                              Page 38
 1   inhaled     steroid,    they   would   have   moderate

 2   asthma.

 3                  There's also some criteria based

 4   upon lung function, and as a consequence, they

 5   are relegated to one of five or six steps for

 6   the treatment, and I'll go over that when we

 7   get to the persistent asthma treatment.

 8                  So, the underlying pathophysiology

 9   of asthma involves three characteristics. One

10   is smooth muscle contraction, which obstructs

11   air flow. The second is mucosal edema, there

12   is an infiltration of eosinophils that are

13   activated     and      then    thirdly,   excessive

14   secretions.

15                 Compare that to a normal airway

16   and you can understand quite readily that the

17   air flow is obstructed in the patient with

18   asthma and it is this obstruction of air flow

19   that causes the symptoms and bronchodilators

20   only attack one of the three components.

21   They relieve smooth muscle contraction, but do

22   not, in any way, relieve the mucosal edema or




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                        Page 39
 1   the excessive secretions.

 2                     So, in a patient who has more than

 3   smooth      muscle       contraction,     using      a    short

 4   acting       bronchodilator           does     not       provide

 5   sufficient relief of the obstruction.

 6   So,    in    the    National      Asthma      and    Education

 7   Prevention guidelines, and by the way, for

 8   those of you who are not familiar with them,

 9   this expert panel has reviewed all of the

10   scientific evidence, all of the published data

11   regarding the disease and its treatment and it

12   came up with an expert panel report that is

13   455 pages long.

14                  This is one of the tables for the

15   treatment     of     asthma      at   home,    and       the

16   cornerstone        is    using    a   short    acting       beta

17   agonist,     up     to    two    treatments, 20 minutes

18   apart, between two and six puffs of an MDI or

19   a nebulizer, and then, based upon the response

20   to the short acting beta agonist, the patient

21   is    classified        as   good,    incomplete or poor

22   response.




                             Neal R. Gross & Co., Inc.
                                    202-234-4433
                                                                     Page 40
 1                 In the incomplete response, which

 2   means that they feel a little better, but

 3   they're     still     wheezy        or     they're      still

 4   coughing, the indication is for adding an oral

 5   systemic corticosteroid, a short course of

 6   prednisone,    for    example,       to    relieve     the

 7   inflammatory component, while continuing the

 8   repeated administration of the short acting

 9   beta agonist.

10                 I might point out that epinephrine

11   is not listed as an alternative in the NAPP

12   guidelines for short acting.             This primarily

13   would be albuterol and pirbuterol.

14   The other important point to note is that if

15   there is a rapid response to the short acting

16   beta agonist, the recommendation is for the

17   patient to proceed to the emergency room, and

18   possibly     even     call     911,        if   they're

19   sufficiently short of breath.             It is clearly a

20   medical emergency, when a patient has a severe

21   asthma    episode    that    does    not     respond    to

22   bronchodilator, and potentially fatal.




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                  Page 41
 1                  You    probably    have    seen    comments

 2   about patients who are found dead, clutching

 3   their inhaler, and if you go back and look at

 4   the stories, these patients typically are not

 5   on a preventer medicine and when they began to

 6   have asthma exacerbations, they had repeatedly

 7   used their bronchodilator.

 8                  I recall many years ago, one of

 9   the models, Krissy Taylor, from Florida, who

10   died   from    asthma,    and    was   found     with   a

11   Primatene Mist clutched in her hands and I

12   remember      the     newspaper    articles      blaming

13   Primatene Mist for her death, and then I had

14   an opportunity to look at the autopsy report

15   and several months before her fatal episode,

16   she had seen a physician who had prescribed an

17   inhaled       bronchodilator        and     Ventolin,

18   albuterol, and she apparently ran out of both

19   of those, and then brought a Primatene Mist

20   and continued to use when she was having an

21   exacerbation and eventually, it was a fatal

22   episode.




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
                                                                     Page 42
 1                   But    it     was   very   interesting     to

 2   note that the news media have blamed these

 3   deaths on the drugs and in fact, if you look

 4   at   all   of    the       literature   and   even   the

 5   epidemics of asthma deaths early in Australia

 6   and England in the 60s and 70s, it's very

 7   clear that these patients die of asphyxiation

 8   and it is not a toxic effect of over-using

 9   albuterol.      It isn't a cardiac death, it's an

10   asphyxiation.

11                   One of the common beliefs among

12   health     care         professionals,         especially

13   allergists,           is       that        nonprescription

14   epinephrine is less effective and more toxic

15   than prescription inhalers and I had heard

16   this for many years and we do clinical studies

17   at the University of Florida and our major

18   subjects are students who want to earn money

19   and we find that they often come to us in a

20   response to an ad and many of them were using

21   Primatene Mist and claiming that it gave them

22   relief.




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
                                                                Page 43
 1   So, that was contrary to what I had read, what

 2   I had been told, what the physicians I worked

 3   with believed.

 4                 So,     we    conducted    a   randomized

 5   controlled    trial     to    actually    evaluate   the

 6   relative          potency       of       nonprescription

 7   epinephrine, and the study model that was used

 8   was nocturnal asthma.

 9   Many of you may know that during the day time,

10   as asthma patient who has airway constriction,

11   airway obstruction that's reversible, has a

12   relatively flat dose response curve for a beta

13   agonist.

14                 In other words, one puff may be

15   all that it takes to bring them to the top of

16   the dose response curve.

17   And so, in that situation, you really can't

18   distinguish between drugs that have different

19   potencies    or    methods    of     delivery that are

20   different, because the patient is at the top

21   of the dose response curve and you usually

22   can't distinguish between two doses of the




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                      Page 44
 1   same product.

 2                    So, we have had an interest, for

 3   several years, at looking at alternative study

 4   designs that would enable us to differentiate

 5   the dose response and one that we stumbled on

 6   was    selecting     out     patients       with    nocturnal

 7   asthma,       admitting     them    to   our    clinical

 8   research center and when they woke up on the

 9   middle of the night with an asthma attack,

10   measure their lung function, give them a dose

11   and repeat that process for a time period, in

12   a cross-over design.

13                   And this is one of the studies

14   that     we     conducted,         comparing        albuterol

15   delivered in doubling doses, starting with two

16   puffs, with epinephrine delivered from a CFC

17   metered dose inhaler, Primatene Mist, and you

18   can    see    here   that    when     the    patients     were

19   admitted to the CRC the night before, their

20   lung function was between 60 and 80 percent

21   predicted, which was the criteria.                 It average

22   about 68 percent predicted.




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
                                                              Page 45
 1   When they woke up in the middle of the night,

 2   their lung function had dropped to an average

 3   of 45 percent.      There were actually a few

 4   subjects who dropped down to as low as 25

 5   percent.

 6                   What distinguishes the patients in

 7   this study from the patients who wind up in

 8   the emergency room from an asthma attack, is

 9   that they are bronchodilator responsive.

10   So, when they wake up in the middle of the

11   night and they take their albuterol or they

12   take Primatene Mist, they respond to it and

13   that is what distinguishes them.

14                You     could      argue    that    these

15   patients should all be on inhaled steroids,

16   but for varying reasons, often, the cost of

17   the   inhaled    steroid   is    an   obstacle   for

18   students to be maintained on it, and so, they

19   just use bronchodilator to get through the day

20   or night.

21   Anyways, we measured the lung function, gave

22   them a dose and repeated that process every 15




                        Neal R. Gross & Co., Inc.
                               202-234-4433
                                                                   Page 46
 1   minutes or between 15 and 17 minutes.              We

 2   allowed two minutes for measurement and lung

 3   function.

 4                     And what you see here is that in

 5   both groups, there is a marked improvement in

 6   lung         function,      that      the     epinephrine

 7   surprisingly was almost as effective as the

 8   albuterol in this situation.

 9   There were only two time points where the

10   differences        were   statistically     significant,

11   and when they woke up the next morning after,

12   they went to sleep after they were relieved,

13   and they woke up the next morning, the lung

14   function was similar.

15                     Now, many people have argued that

16   you    need    longer     and   longer   acting    beta

17   agonists and that is a carry-back to the old

18   days, where beta agonists were used as primary

19   maintenance therapy and then, it was important

20   to    have    a    longer   acting,   and    one   of   the

21   criticisms of epinephrine is, it was too short

22   acting.




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
                                                                  Page 47
 1                   But what you can see here is once

 2   it relieved the attack, the lung function was

 3   pretty normal when they woke up, or at least

 4   as good as it was when they went to bed.

 5                   So the short duration of action of

 6   epinephrine      is    not   clinically    relevant    to

 7   relieving an acute attack, such as this.

 8                   We also measured heart rate and

 9   serum potassium along with spirometry and what

10   you see here is that in the albuterol treated

11   group, the heart rate went up, the potassium

12   went down and in the epinephrine group, it

13   actually dropped.

14                  Now, that's quite contrary to what

15   the   belief    of     health   care    professionals.

16   Don't forget that doctors, in their training,

17   inject epinephrine into the heart of somebody

18   whose heart has stopped, and so they think

19   epinephrine is part of the reversal of cardiac

20   arrest, and so they think of it as a drug that

21   has a profound heart effect, but in fact, when

22   you   deliver    it     by   aerosol,    it's   not   bio-




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
                                                                     Page 48
 1   available, or at least, by this particular

 2   MDI, it's not bio-available, and I'll offer

 3   three possible explanations for why it's not.

 4

 5                   First of all, epinephrine has an

 6   alpha adrenergic receptor activity.                What do

 7   dentists put in local anesthetics to keep it

 8   localized in your gum?          They mix epinephrine

 9   in       it,     and      that        alpha        adrenergic

10   vasoconstrictor property keeps it localized.

11                   Secondly, there is an enzyme in

12   the lung called catechol-O-methyltransferase.

13    Epinephrine      is    degraded      by   COMT,    very

14   rapidly, and thirdly, if any of the drug gets

15   into   the     blood,    it's    rapidly inactived by

16   monoamine oxidase.

17                   So at least in the doses, and this

18   was 14 cumulative puffs in an hour, in a

19   little    bit    more    than    an    hour,   there    was

20   essentially no systemic effects because the

21   drug is not bio-available from the meter dose

22   inhaler.




                        Neal R. Gross & Co., Inc.
                               202-234-4433
                                                                              Page 49
 1                     In    contrast,         albuterol        does    get

 2   into   the    blood.            It      is   both       swallowed,

 3   absorption        occurs       from      the      portion    that's

 4   swallowed,        as    well       as    the      portion    that's

 5   delivered to the airways.

 6                     Well,         when         symptoms         become

 7   unresponsive to inhaled beta agonists, the NIH

 8   guidelines recommend a short course of oral

 9   corticosteroids, and this is a very important

10   component of treating acute asthma.                      It needs

11   to be initiated early enough in the process

12   and in high enough dose.

13                  In our clinic, we give all of our

14   parents a supply of prednisone or prednisolone

15   to   keep    on    hand       at     home.         They     make   a

16   commitment     to       not    administer          it    without

17   talking to one of our doctors or nurses and

18   they have access nights and weekends to call

19   in   and    when       their    child        is    no    longer

20   responsive to albuterol or if it needs to be

21   used more than three times in 24 hours or if

22   it doesn't last four hours, they call us and




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
                                                                            Page 50
 1   our    physician          decides      over    the    telephone

 2   whether to start the oral prednisone and as a

 3   result,       we    have     almost      no    emergency       room

 4   visits and not more than a couple of patients

 5   a year ever get admitted to the hospital.

 6                      Early        in     the     1980s,        Regus

 7   McFadden,       when       he    was    in    Boston,     and    his

 8   fellow, Dr. Fanta, conducted one of the first

 9   double-blind studies examining the efficacy of

10   systemic      corticosteroids            in   patients       with

11   acute asthma, who are treated with repeated

12   doses of short acting beta agonists.

13                      This    study       occurred      in   Boston.

14   Patients were randomly assigned to getting a

15   placebo IV or IV hydrocortisone, in addition

16   to    short    acting       bronchodilator           every    four

17   hours, and what you see here is the lung

18   function markedly improved in the group, much

19   greater improvement in the group that got the

20   steroid in addition to the beta agonist, as

21   opposed to just the beta agonist alone, and at

22   24 hours, there was really a big difference in




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
                                                                          Page 51
 1   the airway patency in these patients.

 2                   This was one of several studies.

 3   There     have        been     studies        in     ambulatory

 4   patients,      in     emergency       room    studies,       all

 5   showing        that       when         patients         become

 6   bronchodilator unresponsive, they respond to

 7   corticosteroids,         and    the     reason      why     they

 8   become    bronchodilator         unresponsive          is    the

 9   airway obstruction is being caused by mucosal

10   edema and excessive secretions, in addition to

11   the smooth muscle contraction, and remember

12   that     the     beta        agonist,        whether        it's

13   epinephrine or albuterol, only will relieve

14   the smooth muscle contraction.

15                   I ran across this study from New

16   Zealand that surveyed patients who came into

17   the emergency room with acute asthma and asked

18   them    how    many    doses     of    short       acting     beta

19   agonists they had taken in the previous 24

20   hours, and it was astounding to find that

21   about 51 percent of the patients had taken

22   between 31 and 61 doses, probably this is each




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
                                                                    Page 52
 1   puff, so that's at the least, it was 15 times

 2   in the last 24 hours, up to 30 times in the

 3   last 24 hours.

 4                 So very clearly, this is the group

 5   that    really     needs    intervention      with    the

 6   corticosteroid and having access without any

 7   intervention to a short acting beta agonist

 8   results typically in the behavior pattern of

 9   repeatedly taking the beta agonist, which may

10   mask the progressive deterioration of lung

11   function    and    it   may    mask   the    impending

12   respiratory failure.

13                 So     it's      very    important        that

14   patients not be, let me word it differently.

15   It's important that patients are taught that

16   it's not just the beta agonist that they need

17   for relief, that they may need corticosteroid.

18                 There     was    a   study    done     several

19   years ago in Canada, where they linked the

20   risk of fatal or near fatal asthma with how

21   frequently patients refilled a prescription

22   for    albuterol.       This    was   under    physician




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                        Page 53
 1   supervision.

 2                    Many       times,     physicians         will

 3   prescribe albuterol with PRN refills or 12

 4   refills, and patients can go into a pharmacy

 5   every few days and fill a prescription, if the

 6   pharmacist hasn't been educated to intervene,

 7   and what this study shows is that the more

 8   canisters of beta agonist a patient uses, the

 9   greater    the     risk      of   dying   from      asthma    or

10   having a near fatal episode, which was defined

11   in the study as needing to be intubated or

12   treated in an intensive care unit.

13                 I might add that at this level,

14   where    there    is     about    a ten-fold increase,

15   that's    filling       a   prescription      one    to    two

16   canisters in a month.

17                 Now, if you go back to the NIH

18   guidelines, patients who have frequent use of

19   a beta agonist need to be on preventative

20   maintenance and from step two to six, you have

21   persistent    asthma        and   in   each    of    these

22   categories, at the very least, there is the




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                      Page 54
 1   requirement      for    an    inhaled       corticosteroid,

 2   either alone or in combination with a long

 3   acting    beta    agonist      in    the     more   severe

 4   categories.

 5                   And     patients          are   evaluated.

 6   They're placed on this therapy, if they have

 7   access to a physician or a nurse practitioner,

 8   and then, we bring them back between a month

 9   and   three     months    after      the     initiation    of

10   therapy, re-evaluate them and either increase

11   the therapy if they're not getting adequate

12   response or decrease the therapy if they're

13   symptom free and well controlled.

14                 Two      complications        occur   in    this

15   process that I've observed in our clinic, and

16   that's first of all, often patients are not

17   getting   the    drug     into      the    lungs.     That's

18   because they're either not taking it or it's

19   because   they're       not   effectively       using     the

20   device, which requires some patient education.

21                 I have no idea how patients can go

22   into a drug store and buy Primatene Mist and




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
                                                                 Page 55
 1   use it, because our patients, when we check

 2   their inhaler technique, it's terrible.              They

 3   have   adopted   all   kinds    of alterations and

 4   delivery of the inhaler that decreases the

 5   amount of drug delivered and it's surprising

 6   to me that they get any benefit at all out of

 7   the over-the-counter use, if they haven't been

 8   taught how to use it.

 9                 So there have been a number of

10   studies showing that inhaled corticosteroids

11   not only relieves symptoms, prevent night time

12   exacerbations, decrease the frequency of beta

13   agonist use, improve lung function, but they

14   also, in the more severe patient, decrease the

15   risk   of   hospitalization     and    this    was    a

16   retrospective     study    that       Jim     Donahue

17   performed,    examining   the    relative      risk    of

18   being hospitalized for asthma in relationship

19   to how many canisters of beta agonists had

20   been   filled,   prescription     filled      in   the

21   previous year, in relation to taking or not

22   taking an inhaled corticosteroid.




                      Neal R. Gross & Co., Inc.
                             202-234-4433
                                                                         Page 56
 1                   And what they found is that in the

 2   patients who filled more than eight canisters

 3   of albuterol in the previous year, they were

 4   seven times more likely to be admitted to the

 5   hospital.

 6                   Now, you could argue that well,

 7   maybe    it's    because      they're      more    severe

 8   disease,    but    if     they    were     also    taking      an

 9   inhaled     corticosteroid,          that        risk    was

10   drastically reduced.

11                   So in addition to the day-to-day

12   relief of symptoms and improvement in lung

13   function    that        an    inhaled    corticosteroid

14   provides,   it     also      decreases     the    risk    of

15   hospitalization and it decreases the risk of

16   death.

17                   This    is    a   study,    again,      from

18   Canada, where they looked the rate ratio of

19   death from asthma in relationship to how many

20   canisters of an inhaled corticosteroid had

21   been filled in the previous year, and you can

22   see quite clearly, that those patients who




                        Neal R. Gross & Co., Inc.
                               202-234-4433
                                                                     Page 57
 1   infrequently filled their prescription, had a

 2   very high risk of dying from asthma and that

 3   patients     who    filled    it     almost    monthly,

 4   essentially had no risk at all, and in fact,

 5   the ratio was below one.

 6                  So     very     clearly,        the     5,000

 7   patients in the United States who die each

 8   year from asthma are preventable deaths, if we

 9   could      only     get    them       to     take     inhaled

10   corticosteroids.

11                 So    what     about    the     alternative

12   nonprescription product?           This is Primatene

13   tablets.    It's also available under generic

14   names, like Wal-Mart's brand, etcetera.               This

15   particular product contains 12.5 milligrams of

16   ephedrine and 200 of guaifenesin.              As you'll

17   see in a minute, ephedrine is a very weak

18   bronchodilator,      especially       when     it's   given

19   orally, it's significantly less effective than

20   beta 2 selective agonist.

21                 It also has a lot of side effects,

22   when you increase the dose.           It has CNS side




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                  Page 58
 1   effects.     It's called poor man's amphetamine.

 2   College students will take several tablets to

 3   stay up all night long studying for a test.

 4                  It contains guaifenesin and why it

 5   does that and why the FDA allows that, I have

 6   no idea, because if you look at the double-

 7   blind placebo controlled trials, guaifenesin,

 8   neither thins sputum nor does it increase the

 9   volume of sputum and why it's in this product,

10   in fact, maybe someone here can answer that

11   question     for    me,   but   it   has    no    efficacy

12   whatsoever.

13                  This is a study that Don Tashkin

14   did in 1975.       You ask why am I looking at such

15   old data, because this is a very old drug that

16   has not been prescribed by physicians for my

17   entire career, which is over 30 years.

18                  But this is a study that Don did,

19   where   he    compared     placebo.        This    was   a

20   randomized cross-over design in patients with

21   asthma, using specific airway conductants, 2.5

22   milligrams     of    terbutaline     and    oral beta 2




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                         Page 59
 1   selective agonist that is much, much weaker

 2   than the inhaled form.

 3                  So you can imagine of they had

 4   included an inhaled ephedrine, what it would

 5   look like.

 6                  This        is       ephedrine       at         25

 7   milligrams,       which    is     two   tablets    of     the

 8   Primatene    Mist.         Yes,     it's   significantly

 9   better than placebo, but a whole lot less

10   effective    than     oral      terbutaline,      and    Mike

11   Weinberger, in 1975, looked at the effects of

12   theophylline      ephedrine       combinations.          The

13   product which was Mirax, was very popular at

14   that time.    It was a mixture of theophylline,

15   ephedrine    and    hydroxyzine,        and   he    took

16   children who were in a residential treatment

17   center at National Jewish Hospital, where they

18   were in bungalows and had a nurse in every

19   bungalow and they were able to measure their

20   symptoms    and    to     treat    them    when    they    had

21   symptoms.

22                 They were randomized in a double-




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                            Page 60
 1   blind       manner        to     placebo        hydroxyzine,

 2   ephedrine, theophylline alone, ephedrine and

 3   theophylline         in    combination         or   the     actual

 4   ingredients that were in Mirax and the point

 5   in     wanted   to     make      is    that     there     was    no

 6   significant difference in the frequency of

 7   symptoms, with ephedrine versus placebo.

 8                   When       they    got       symptomatic,       they

 9   treated      them     with     a   non-selective          beta

10   agonist,     isoproterenol,            at    the    time.        We

11   didn't have albuterol back in those days, and

12   there was no significant difference there.

13                   If    they     didn't        respond      to    the

14   isopreterenol, they injected epinephrine and

15   if   they    didn't       respond       to    that,     they

16   substituted known medicines for the double-

17   blind medicines and the important message is

18   that     ephedrine         did        not     relieve       asthma

19   symptoms, but when combined with theophylline,

20   it produced a synergistic toxicity, not shown

21   here, but that's one of the reasons why FDA

22   did remove theophylline from the over-the-




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
                                                              Page 61
 1   counter products, such as Primatene tablets.

 2                 The bottom line message is once

 3   epinephrine is removed, there won't be any

 4   effective    over-the-counter     product,     because

 5   this is certainly not going to relieve an

 6   asthma attack.

 7                 So what I've covered here are some

 8   of the essential components of asthma and the

 9   important take-home message is that asthma is

10   just not a bronchospastic disease, that it has

11   an important inflammatory component and that

12   bronchodilators do not reverse that.

13                 The    bronchodilator     response   to

14   epinephrine is indeed, effective, and safe, so

15   we   are   removing    an   effective    and   safe

16   bronchodilator, that clearly, asthma requires

17   corticosteroids, short acting bronchodilator

18   response is poor.      We need to add a systemic

19   corticosteroid.      Inhaled corticosteroids do

20   not relieve acute asthma symptoms, only oral,

21   as they probably get to the smaller airways

22   and then also importantly, is if we could




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                             Page 62
 1   accomplish this, this is what the National

 2   Asthma Education Program has been trying since

 3   around 1990, and that's to get patients on

 4   inhaled steroids when they have persistent

 5   asthma, because it has marked improvements,

 6   including life saving characteristics.

 7               Lastly,    the     oral   nonprescription

 8   products, in my opinion, should be taken off

 9   the market, and I thank you for your attention

10   and I'll be glad to answer questions. Do I

11   have time for questions?

12              CHAIR SEYMOUR: Yes, I'll ask if

13   anyone has any questions?

14              DR. PARKER: Could you give us a

15   little bit of insight into cost, just, you

16   know, relative?

17              DR.     HENDELES:    Sure,   a   Primatene

18   inhaler is about $18 at a Wal-Mart type store,

19   and if a doctor prescribes Ventaline HFA/MVI

20   and they take it to Wal-Mart, they get it for

21   $9.95.

22              That's not true for the other drug




                       Neal R. Gross & Co., Inc.
                              202-234-4433
                                                                        Page 63
 1   stores.     Apparently, Wal-Mart made a special

 2   pact with GSK and the 60 puff canister that

 3   was intended for hospital distribution, is

 4   what    Wal-Mart        sells     for    $9.95      and        a

 5   conventional prescription has 200 puffs and

 6   costs   somewhere       around    $35   to   $40    for      an

 7   albuterol HFA/MDI.

 8                  DR. PARKER: And steroids?

 9                  DR. HENDELES: Well, prednisone is

10   about a penny a tablet and an inhaled, so it's

11   very cheap, in terms of for acute relief.               Of

12   course, you can't continue to give patients

13   that because of the risk of systemic effects.

14                 Inhaled     corticosteroids        vary     in

15   the cost, depending upon who is buying it at

16   our hospital, just as an example, because we

17   have a disproportionate share of under-served

18   patients, we get Teva's Qvar for about $2 a

19   canister.    The drug stores in town pay about

20   $40 for that same canister.

21                 So   we    can     actually    make   that

22   available to those patients and even if we




                        Neal R. Gross & Co., Inc.
                               202-234-4433
                                                             Page 64
 1   have to swallow the cost, it's pretty small,

 2   but I think it's quite variable if a patient

 3   has to fill a prescription out of pocket, for

 4   an inhaled corticosteroid.        It's often between

 5   $60 and $100.

 6                  If they get a combination product

 7   like Advair, it's $170 to $200.         So it varies.

 8    Co-pays vary too.       If you have a prescription

 9   benefit, they may have one of the brands on

10   the preferred tier, and so you get it for $20

11   co-pay, and if you insist on having one that's

12   not on their preferred drug list, you may pay

13   a $50 co-pay for a month's supply.

14               So it's really variable.

15               DR. PARKER: So just to go over

16   this one more time, so I understand it.        So if

17   you were someone who went and bought this

18   Primatene Mist every now and then, and you

19   were paying $20 every now and then to get it,

20   or   however       often,        the    alternatives,

21   financially,     would     be,     if   you   had   a

22   prescription, you could go to a Wal-Mart.




                       Neal R. Gross & Co., Inc.
                              202-234-4433
                                                                 Page 65
 1                 Has that been picked up by other

 2   chains that are matching that program or is it

 3   just that?    I'm just looking nationally, at

 4   access, sort of in financial barriers.

 5                 DR. HENDELES: Yes, and to the best

 6   of my knowledge, there was a special deal made

 7   between GSK and Wal-Mart and I have not seen

 8   that 60 puff canister dispensed anywhere else,

 9   and to the best of my knowledge, it's not

10   available anywhere except from Wal-Mart.

11                 But    what   you're     getting   at   is

12   somebody who is a mild intermittent asthma

13   patient, who successfully uses Primatene Mist,

14   actually, in the long run, would save money by

15   going to a physician, to a nurse practitioner

16   or even to a county health department, getting

17   the prescription to Ventolin and going to Wal-

18   Mart.

19                 DR. PARKER: And I had one other

20   question.    You mentioned, and I'm curious if

21   you   know   anymore    about    it,    that   some

22   prescribers     will     write     for     refills     on




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                         Page 66
 1   inhalers' PRN.       Do we have any numbers about

 2   how commonly that is done, as a practice and

 3   whether      or     not      there         are    a    lot     of

 4   prescriptions, PRN for inhalers out there,

 5   meaning that, you get it every now and then

 6   and if you happen to be on file, you can walk

 7   in and you can get it?

 8                    Is this a prescribing practice on

 9   the part of physicians or on the part of

10   pharmacies,       that    varies      state      by   state,

11   location by location?           I'm just very curious

12   about that.

13                 DR.     HENDELES:        I    don't     have   any

14   scientific    data,       but    I    trained      pharmacy

15   students    in     Florida      and    I    see    them   at

16   continuing education meetings and I interact

17   with them on behalf of our Pulmonary Division,

18   related to refills, and I would say that it's

19   common    place.     There      are    physicians in our

20   division    that     will    write      12 refills, even

21   though the pre-printed prescription says do

22   not refill more than one canister every two




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                      Page 67
 1   months without calling us.

 2                    You know, so I mean, I think it's

 3   commonplace.

 4                    DR. LEONARD-SEGAL: Thank you for

 5   your talk, Dr. Hendeles.           I wanted to go back

 6   to a comment that you made about people not

 7   effectively using the inhaler and how you're

 8   not     sure   how    anyone     uses   the    OTC    inhaler

 9   because they don't get instructions on how to

10   use   it   and    they    seem    to    make    a    lot    of

11   mistakes.      I hope I'm paraphrasing sort of

12   correctly.

13                   I'm     wondering       if     you     have

14   information on the type of education that the

15   typical    patient      receives    when      they    are

16   prescribed an inhaler and how effectively they

17   use the prescription inhalers compared to the

18   OTC inhalers, because, you know, these old

19   inhalers were not tested for actual use.                I

20   think that a lot of the prescription inhalers

21   also have not been tested for actual use, in

22   terms    of    how    consumers    or    patients      can




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
                                                                           Page 68
 1   actually       manipulate         and    effectively         self-

 2   administer the drug.

 3                    And so, I'm always curious about

 4   being     in    the    nonprescription           world,       how

 5   effectively the prescription world takes care

 6   of that education process by comparison.

 7                    DR.     HENDELES:        Not    very       well.

 8   There's actually been a number of studies,

 9   evaluating       patient      techniques         in     various

10   settings,       in    emergency         room,    pharmacies.

11   There's    actually         been    studies       evaluating

12   pediatric       residents      and       how    they    use    the

13   devices,       and    overwhelmingly,           all    of    the

14   studies show a very high rate of inappropriate

15   or ineffective use of meter dose inhalers.

16                    There       is     other        devices       like

17   breath-actuated          inhalers          and    dry    powder

18   inhalers where patients can be taught once and

19   they    continue       to    come       back,    using      good

20   technique.

21                    But in my own personal experience,

22   one of the things I do in the clinic, my




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
                                                                          Page 69
 1   students and I teach every new patient how to

 2   use the devices and when they come back for a

 3   return visit, we check every patient, every

 4   time and it is amazing how poorly they use

 5   MDIs.

 6                    And so we avoid MDIs when we can

 7   in the older patients and use chambers or

 8   chambers       with    masks       in    addition,     which

 9   eliminates the problem with the MDI.

10                   But it is a major problem.               Dr.

11   Liu, you probably have some experience with

12   that too, and maybe you can add a comment.

13                   DR. LIU: I think it is something

14   that is anyplace that specializes in asthma

15   care, has a program, just like Dr. Hendeles is

16   talking about, to teach patients because this

17   problem    is    common       and       re-enforcement       is

18   necessary.

19                   I     would    sort       of   just    add    that

20   patients will take a bronchodilator until they

21   get an effect. I mean, in other words, that

22   they    know    or     had    an    experience        with    the




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
                                                               Page 70
 1   effect, the immediate effect, and usually,

 2   they're    trying    to    use   it,   obviously,    to

 3   relieve symptoms, and that can lead to abuse,

 4   because, you know, they get relief and they

 5   continue to use it and abuse it in large

 6   amounts    and   then     they   get   into   trouble,

 7   because they're not really on the appropriate

 8   medication.

 9                 But in general, it's more of a

10   problem with inhaled corticosteroids, where

11   the effect is not immediate, in terms of what

12   they can experience, you know, as an immediate

13   relief of their symptoms, as opposed to a

14   bronchodilator, which they will take until

15   they get something.

16                 So even though they may not be

17   getting    the      optimal      delivery     of    the

18   bronchodilator to the lower airway, they will

19   take it until they get some sort of effect.

20                 DR. LEONARD-SEGAL: Do you want to

21   go next?   Okay.

22                 DR. REIDENBERG: If I can just join




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                 Page 71
 1   in.     A friend of mine has a pediatric practice

 2   in    the   Harlem     neighborhood      in   Northern

 3   Manhattan and a point he's made in this is

 4   that it's very difficult to teach a 16 year

 5   old mother how to use any of these inhalers

 6   for her two year old, asthmatic child, and in

 7   fact, in a survey that was done, about half of

 8   the patients being treated in Harlem get oral

 9   albuterol, because the inhaler just doesn't

10   work for them.

11                   DR.    HENDELES:   And    they   probably

12   don't    have    access    to   chambers with masks,

13   which is how we deliver it, the MDI, through a

14   valve holding chamber. Well, I can tell you

15   that that's the problem.

16                   Often, Medicaid doesn't reimburse

17   for that, but they won't pay for $14 chamber,

18   but they'll pay for $150 compressor nebulizer.

19                   DR. LEONARD-SEGAL: I also had one

20   other comment that I wanted to make.

21                   You had talked about the Primatene

22   oral product that's combined with guaifenesin,




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
                                                                      Page 72
 1   and I have a copy of the Code of Federal

 2   Regulations sitting on my lap here.

 3                    The    ephedrine      products    are     not

 4   generic     or    innovator.        They're      actually

 5   monograph, all of them.          So in fact, they're

 6   made   by    anyone      using   any     trade    name,

 7   essentially.

 8                    So that's just something that I

 9   thought I would bring up and the other thing

10   is, in scanning through, I can't find where

11   under the final monograph, the combination of

12   ephedrine and guaifenesin is actually allowed,

13   under the Code of Federal Regulations.

14                    So we're going to have to check on

15   that. I have a couple of colleagues from the

16   Division         of     Nonprescription       Regulation

17   Development sitting in the audience over here,

18   who write the monograph and maybe they can

19   comment and help me out here, and let me know

20   if this is allowed or not allowed.               This is

21   Merena Chung.

22                    MS.    CHUNG:   The    combination       of




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
                                                                     Page 73
 1   guaifenesin and epinephrine with guaifenesin

 2   is allowed under the combination policy.               Yes,

 3   the combination of epinephrine and guaifenesin

 4   is allowed under the combination policy.

 5                But however, in 2004, you know,

 6   around 2004 or 2006, I can't remember the

 7   exact date, we have published a proposed rule

 8   to   withdraw     this   combination      as     being    an

 9   irrational combination.

10                So we're in the process of getting

11   the comments and re-evaluating the comments

12   and making a final decision.

13                DR.    HENDELES:      I'm    glad    to     hear

14   that, but one could entertain the idea of

15   whether or not that should be replaced with

16   albuterol or terbutaline, which are orally

17   bio-available and while not as effective as an

18   inhaler,   they    clearly    have    a    substantial

19   bronchodilator     effect    and    are    dirt    cheap,

20   because they're off patent.

21                MS.    CHUNG:    Whether      it    could     be

22   replaced by albuterol and terbutaline dose, we




                        Neal R. Gross & Co., Inc.
                               202-234-4433
                                                        Page 74
 1   need to go through a rule making process and

 2   again, so far, we have not have received any

 3   petition or anything, to put that product into

 4   the OTC monograph, or the OTC.

 5               DR. LEONARD-SEGAL: I would add to

 6   that as well that, another possibility for

 7   that process would be if they switched and

 8   became a new drug application under the OTC. A

 9   new OTC drug switch, in other words.

10              So    there     are   a   couple   of

11   possibilities for how that could potentially

12   happen.

13              DR. HENDELES: And in fact, I don't

14   know what the economics are, but I've been

15   told that Primatene Mist sold something like

16   60 million canisters last year.

17              So there may even be an economic

18   incentive for one of the companies to pursue a

19   beta 2 selective agonist by the oral route.

20              CHAIR SEYMOUR: I think if there

21   are no additional questions, we'll move on.

22   Thank you, Dr. Hendeles.




                     Neal R. Gross & Co., Inc.
                            202-234-4433
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 1                Our    next   presentation       is     Dr.

 2   Marcus Reidenberg, who is going to give us

 3   perspective on the under-served population.

 4                DR.    REIDENBERG:     Thank     you     very

 5   much.    I   thought    Les    gave    a    beautiful

 6   presentation.   He has been a terrific clinical

 7   pharmacologist,     active    in   this     area     for

 8   decades and I've really respected his work.

 9   It's wonderful to hear him present it like

10   this.

11                To get a little personal for a

12   minute, a number of years ago, I had a medical

13   student working with me, who had gotten a

14   Master of Public Health at Columbia, before

15   she came to Cornell Medical School.

16                She had worked with asthmatic kids

17   in the homeless shelters in Manhattan in New

18   York City and was struck how many of them had

19   asthma and how poorly it was controlled and

20   was speculating about the fact that because of

21   the chaos in their lives, the need for the

22   refill   prescription        was   a       barrier     for




                        Neal R. Gross & Co., Inc.
                               202-234-4433
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 1   maintenance.

 2                   And so anyway, I thought that made

 3   sense and I wrote what amounted to a citizen's

 4   petition      to    the    FDA     and nothing happened,

 5   until they invited me to come talk at this

 6   meeting.      So that's kind of how I got here and

 7   I thought I'd go over some data with you.

 8                   DR. LEONARD-SEGAL: Dr. Reidenberg,

 9   it     had   nothing      to     do    with    the    citizen

10   petition, your invitation here today. I just

11   want to clarify that.

12                   DR.       REIDENBERG:         Well,     I    am

13   delighted to be here and say what I think

14   about it.

15                   DR.    LEONARD-SEGAL:          Two    separate

16   entities.

17                   DR. REIDENBERG:          Here is actual

18   data    on    the   numbers       of    poor    people,     the

19   poverty      rate   in     the    United      States    over    a

20   period of time.        There are an awful lot of

21   poor people here.

22                   These are the thresholds that we




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
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 1   use, so a family of four, for an income under

 2   $22,000, by definition, is poverty, by the

 3   Federal level, and I hope we'll agree that

 4   this isn't set too high.

 5                Here   is   the    income    distribution

 6   for Americans and what you can see is, that

 7   over half of us have incomes of $40,000 or

 8   less a year, and you just heard what the cost

 9   of some of these medicines are.

10                Here is poverty rate by children

11   and you see that the majority of poor people

12   in America are poor children.

13                Now,   let's    get   to    the   homeless

14   people in the municipal shelter system in New

15   York City, which is a sample that various

16   advocacy groups have access to, and here you

17   see the actual numbers of poor people in the

18   shelter at any given time, and so the most

19   recent was over 36,000, and I'm told that all

20   these slides will be posted on the website

21   somewhere.     So   you'll     have   access    to   the

22   numbers.




                     Neal R. Gross & Co., Inc.
                            202-234-4433
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 1                Here, you see the census, again,

 2   in a given period of time, in the homeless

 3   system in New York City and as you see, almost

 4   16,000 of them are children.

 5                Here is the prevalence of asthma

 6   in the United States, just under six percent

 7   and if you're under 18, it's seven and a half

 8   percent.   So the children are more likely to

 9   have asthma than middle age and grown-ups.

10               Here, you see the prevalence by

11   age and in every age group, it's going up and

12   you see the five to 14 year olds have the

13   higher prevalence of asthma than any other age

14   group, so that we can really look at this as

15   an illness that focuses on children.

16               Now, here are studies of asthma in

17   children, in these shelters, and let me say

18   parenthetically,    that    the   families   in   the

19   shelters   aren't     the     same    continually.

20   Families go in, families come out.

21               So that I would submit that this

22   is also representative of what I will call




                     Neal R. Gross & Co., Inc.
                            202-234-4433
                                                                   Page 79
 1   pre-shelter families, that it's representative

 2   of the same families post-shelter, that it's

 3   representative of the families who have lost

 4   their homes, but are now able to live with

 5   friends    or    relatives,    so    they're    not     in

 6   shelters and I hope we can look at this really

 7   as more representative of the poor and the

 8   disadvantaged         urban   people,    than    simply

 9   homeless people in New York City.

10                   The     original     study     that     Dr.

11   McLean, who was my student did as an MPH

12   student, 740 children were reviewed.            Forty

13   percent of them had asthma, 67 percent with a

14   prior physician diagnosis, and 33 percent with

15   symptoms consistent with moderate or severe

16   persistent asthma.

17                   This was updated a few years later

18   and the absolute prevalence was found to be 35

19   percent, with larger numbers, as against the

20   national figure in children of seven and a

21   half percent, and we can discuss why poor

22   people    have    more    asthma    than rich people.




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
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 1   That's a different topic.

 2                    Eighty-four        percent       of     the

 3   children in shelters had a prior diagnosis of

 4   asthma.    Eighty-five percent of them were on

 5   no anti-inflammatory medication and 63 percent

 6   had had emergency department visits in the

 7   prior.    They did have contact with the medical

 8   system.

 9                    Here,   in   the    next   are    several

10   studies done by a national cooperative group

11   of very conscientious pediatricians, taking

12   care of inner-city children, trying to improve

13   their asthma care.

14                 This was 1,000 patients in a two-

15   year    study,    the    usual   care   versus     the

16   intervention, and what you can see is, that

17   the    intervention      decreased    the     unscheduled

18   visits with doctors by a little bit, decreased

19   the emergency room visits by a little bit,

20   decreased the hospitalization days by a little

21   bit.

22                 And so if we ignore the usual care




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                    Page 81
 1   and look at the intervention, this is the best

 2   a demonstration project could do.

 3                  Now, here we have another one, who

 4   are children who had been hospitalized or gone

 5   to an emergency department for asthma in the

 6   six months prior to the study.             Serious kids.

 7    Major effort, and again, if we look at the

 8   intervention group, in each instance, it's a

 9   little better than the usual care, and it

10   shows the best that we can do, and here is my

11   last   study    from    the      literature and again,

12   another intervention and control.

13                  The      intervention          group      is

14   certainly   better,        but    again,    look   at   the

15   actual manifestations, what we're able to do.

16                  Now, this is really what I think

17   is the best that we can do, under the present

18   system of care for these inner-city pediatric

19   patients and this is different from what Dr.

20   Hendeles presented, that he can do in his

21   catchment area in Florida, which is terrific.

22                  He's    a    dedicated      person.      He's




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
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 1   first rate and it makes a difference and he's

 2   shown it.

 3                   But this is the reality in New

 4   York City.      Fewer than 10 percent of children

 5   received asthma medicine, only 10 percent with

 6   severe       persistent       asthma   received   anti-

 7   inflammatory medicine, yet 60 percent of these

 8   children had an emergency department visit in

 9   the prior year, 58 percent of moderate or

10   severe asthma with prior MD diagnosis, had an

11   emergency department visit in the prior year.

12                  All I can say is, this is our

13   reality.     It's not that different from what I

14   showed you for the inner-city studies.

15                  Now,     Dr.   McLean   was    speculating

16   about the causes in her paper, and for the

17   homeless kids now, lack of access to a medical

18   home, lack of continuity of care, emergency

19   department physicians thinking somebody else

20   is responsible for their care, and something

21   that   she    and   I    talked   about,     without   her

22   actually putting in her paper is, that the




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                   Page 83
 1   life of a child and family with low income is

 2   just     so    chaotic    that   compliance     with    the

 3   present methods of care of chronic illness is

 4   impossible for them.

 5                    And so some speculations.        If we

 6   look at a minimum wage worker, if they're

 7   working five days a week, eight hours a day,

 8   five days a week, 50 weeks a year, then their

 9   income is $20,000 a year.          Our poverty level

10   is   28-something.         I'm   sorry,   it's    22-

11   something.

12                    If somebody is making $10 an hour,

13   then it's $28,000 a year.

14                    I showed you the distribution of

15   income    level     and   families   in   the    United

16   States.

17                    Now, the present system of care

18   requires taking the asymptomatic child to the

19   doctor, and this has to be a priority for the

20   parent.       This means the parent must be absent

21   from work to take the child to the doctor or

22   the clinic.




                         Neal R. Gross & Co., Inc.
                                202-234-4433
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 1                   The parent must also go back to

 2   the   original     pharmacy         for    refill     of     a

 3   prescription, which must have been written

 4   less than a year ago, and again, I point out

 5   and I'm sure that I don't need to go into more

 6   detail on how chaotic the lives of many of

 7   these poor families are.

 8                   Now,    the       more    I   thought      about

 9   this,     it   raises    a    question,        is    needing          a

10   prescription for a refill, containing medicine

11   for   continuing       maintenance         treatment       of     a

12   chronic illness, a barrier?

13                  I suspect the answer is yes, but I

14   don't know. I have no data.               If it is a

15   barrier, then how much of a barrier is it,

16   really?

17                  So far as OTC bronchodilator use

18   in asthma, this is what I could gain from the

19   literature.

20                  This     is    a    study,     a     survey       of

21   asthmatics, 15 were exclusive OTC users, 13

22   used both prescription and OTC medicine, and




                        Neal R. Gross & Co., Inc.
                               202-234-4433
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 1   at   least   according   to   these   authors,    the

 2   exclusive OTC users apparently were people

 3   with intermittent asthma, who were appropriate

 4   for a bronchodilator use.

 5                 This is another study of 25 low

 6   income urban adults with persistent asthma,

 7   requiring steroids, were interviewed.       Eighty-

 8   four percent used complimentary or alternative

 9   medicine,    often   with   bronchodilators,     76

10   percent under-used their adrenergic agonist by

11   guideline criteria.

12                For bronchodilator use, this was

13   in a Wyeth paper that was on the internet.

14   They said five million canisters were sold in

15   2004 and they did an internet survey and the

16   whole methodology. This was just a summary and

17   a briefing document.     I don't know that the

18   work was published, but 30 percent of the

19   asthmatics that they surveyed reported using

20   OTC inhaled epinephrine.

21                Now,    Wednesday    afternoon,      IMS

22   Health gave me more recent data and so, this




                      Neal R. Gross & Co., Inc.
                             202-234-4433
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 1   is   data    from     the     following    IMS    Health

 2   Incorporated        service,     Information      Resources

 3   Incorporated and this includes everything but

 4   the medicine dispensed or distributed to Wal-

 5   Mart,     and       we're      talking     about       inhaled

 6   epinephrine.

 7                   In 2008, there were 3.65 million

 8   units distributed.          In 2007, there were 3.82.

 9    In the first half of 2009, there were 1.82

10   distributed      with    an    annual     rate    of   3.64

11   million     units    distributed     in     the    United

12   States, excluding those distributed to Wal-

13   Mart, and those are the figures that I could

14   come up with on actual use.

15                   The issue has been raised about

16   people using their inhalers too much and dying

17   from it, the figure of 5,000 per year was

18   quoted, but the issue here is, do deaths from

19   asthma    occur     in   people    who     just    treat

20   themselves with over-the-counter medication,

21   or in patients being treated by a physician?

22                   The two asthma deaths that I know




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
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 1   personally about were in patients treated by

 2   excellent physicians.          The patients had bad,

 3   progressive      disease      and     we   didn't have an

 4   effective technology to deliver.                 Whether they

 5   should    have    gotten      to     the   emergency       room

 6   sooner, whether had they started oral steroids

 7   at home, when it got worse, could have made a

 8   difference?      Probably.

 9                   But    again,      this    is     the    reality

10   that we're living with at the present time and

11   I'm not aware of any data, even the patient

12   that Les described was being treated by a

13   physician, for whatever reason, didn't get the

14   prescribed medication, but got OTC inhaler and

15   then died with it.

16                 And      so,    I'll    again,      raise    the

17   question, is needing the refill prescription a

18   barrier   for    the     maintenance        therapy      of   a

19   chronic disease?

20                 And      this    raises      the    even    more

21   interesting question, is lack of treatment of

22   a chronic disease, and here, we're talking




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
                                                                       Page 88
 1   about asthma, better or worse for the patient

 2   than     inadequately        supervised        treatment?

 3   That's the principle.

 4                   Our     present    practices        basically

 5   say    yes,    no   treatment      is    better      than

 6   inadequately supervised treatment.                 You have

 7   to go back to the doctor.           You have to get the

 8   refill prescriptions.         You have to go to the

 9   pharmacy that has the prescription on file, to

10   get the refill.

11                   Let's       look        at     some         OTC

12   alternatives.       The PDR for nonprescription

13   drugs in 2008 lists 48 different decongestant

14   and combinations and 45 antihistamines and

15   combination      products.         These     are    branded

16   products.      They're also generic decongestant

17   antihistamine products.           The labeling may not

18   say they're for asthma, but people take them

19   for asthma.

20                   They're       ephedrine         combination

21   products      and   we're    not    even talking about

22   stuff available on the so-called pharmacies




                           Neal R. Gross & Co., Inc.
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 1   that are on the internet.

 2                  Interesting,             there's        a     book,

 3   Medicinal Plants of the World.                Volume two is

 4   the one that has the index.               You didn't have

 5   the index in volume one, and there are three

 6   out of 23 plants described in this book in

 7   great detail, where each of these has been

 8   subject   to       a    clinical       showing efficacy in

 9   asthma in people published in medical journal.

10                  This       work    is    primarily          done   in

11   India.     The         publications      were     in       Indian

12   medical journals.          But I suspect that in this

13   country, none of us academic investigators

14   give a ditty about these plants, and so, we

15   wouldn't think to investigate them anyway.

16                  I       can't   tell     you   anymore         than

17   that, other than, this is part of the lore of

18   the alternative and complementary world.                      I

19   have no idea how much it's used.

20                  Here are the guidelines that Les

21   already   presented         and    this    is     a    little

22   abstract from some of them, and basically, it




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
                                                                         Page 90
 1   says early treatment of asthma exacerbation is

 2   the best strategy for management and that what

 3   you should do at home is to increase the

 4   inhaled short acting beta agonist and in some

 5   cases, add a short course of oral steroids,

 6   and I think we all agree that this is the best

 7   therapy.

 8                 Now, there is certainly lots of

 9   asthmatics,      self-treat          or     fail    to        get

10   treatment.      As    a    physician,       I   have     no

11   responsibility for any of these people, if

12   they don't come to see me.           So I have no

13   doctor/patient        relationship          with     them.

14   They're not my responsibility.            They're not my

15   problem.

16                 But         if      we         talk         about

17   responsibility for the health of a population,

18   then we've got responsibility for everybody in

19   the population, not just those that come to

20   see   us   doctors,    and     the    FDA    is    such    an

21   organization.

22                 Inhaled albuterol is as good as




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                   Page 91
 1   inhaled epinephrine.         Les showed that it's

 2   really better, and it's better than all the

 3   other       products        available      without        a

 4   prescription for treating acute attacks of

 5   asthma.

 6                    Our present policy is no treatment

 7   is      better     than     inadequately     supervised

 8   treatment for people with asthma.           I think

 9   it's not.     I don't have any data.

10                    But I'll say that people who think

11   it is better also don't really have any data,

12   or at least if they do, I haven't seen it

13   published anywhere.

14                    And so I think inhaled albuterol

15   should be made nonprescription, as well as

16   prescription, so people can obtain it without

17   prescription       and    third   party   payers   will

18   continue to pay for it under present customs

19   of paying for prescription medication only.

20                    I happen to think the same for

21   inhaled steroids, for the same reasons.            I

22   think    inadequately       supervised    treatment    is




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                             Page 92
 1   better than no treatment for asthma.

 2                I think the message is for the FDA

 3   to disseminate or that inhaled albuterol is

 4   the alternative to inhaled epinephrine and I

 5   think this is true, whether it's over-the-

 6   counter    as    well     as   prescription       or

 7   prescription only.

 8                I think the second message is that

 9   it requires proper technique to get benefit

10   from the inhaler and I think the third message

11   has to be that if the asthma doesn't improve,

12   get some medical attention promptly.       I think

13   these are the key issues.

14                I think we need research to learn

15   how much of a barrier the need for a refill

16   prescription is, for the continued maintenance

17   therapy of additional chronic diseases, and a

18   couple of examples, diabetics certainly need

19   insulin,   and   that's    over-the-counter.   It's

20   nonprescription, and yet, if ever there is a

21   disease     where       good    supervision       and

22   comprehensive     management     really   makes    a




                      Neal R. Gross & Co., Inc.
                             202-234-4433
                                                            Page 93
 1   difference in outcome, it's diabetes, yet as a

 2   society, we kind of decided that it's better

 3   for diabetics to get insulin and not go into

 4   diabetic coma, than to not be able to get

 5   insulin when they need it.

 6                 Hypothyroidism doesn't get better

 7   and patients need thyroxine and people with

 8   adrenal insufficiency need fludrocortisone.

 9                 Then    I'll   raise   the   question,

10   should   an   empty   bottle    of   a   maintenance

11   medicine with the patient's name on it be

12   sufficient evidence of medical supervision, to

13   enable it to be refilled?

14                 Let me add that to the best that I

15   could find out in my state, New York, and with

16   respect to the federal government, there are

17   no   regulations      on     expiration     of   a

18   prescription.

19                 This idea that you can't refill it

20   after a year is custom.       Third party payers

21   make it a rule, but the best that I could find

22   out and the pharmacist running our hospital




                      Neal R. Gross & Co., Inc.
                             202-234-4433
                                                                     Page 94
 1   drug information center could find out, there

 2   isn't any government regulation that requires

 3   it.     This    is     something      we    just    do   to

 4   ourselves.

 5                  Is there actual data to answer the

 6   question, is the need for a prescription a

 7   barrier to continued maintenance therapy for

 8   patients with chronic illnesses?

 9                  And so, the issue really, is no

10   treatment better or worse than inadequately

11   supervised     treatment      for   the      maintenance

12   therapy of chronic diseases and I'll leave you

13   with the statement the professor of medicine

14   told our graduating class, it isn't what we

15   don't know that gives us trouble, it's what we

16   know that isn't so.         Thank you very much.

17                  CHAIR    SEYMOUR:      Thank      you,    Dr.

18   Reidenberg.           Are     there        any     clarifying

19   questions for Dr. Reidenberg?              Dr. Hendeles?

20                  DR. HENDELES: That was excellent,

21   Mark.

22                  DR. REIDENBERG: Thank you.




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
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 1                  DR.    HENDELES:     And    I     like    that

 2   question.     I think that's very profound.

 3                  Just       a        few          points         of

 4   clarification.       You listed it as alternatives,

 5   antihistamines and decongestants and there's

 6   plenty   of    placebo    controlled,          randomized

 7   controlled trials showing that they don't help

 8   asthma at all.

 9                  DR.       REIDENBERG:             I'm       not

10   questioning that, but if we're talking about

11   what's there that the law says you can try,

12   they exist.

13                 DR. HENDELES: Okay, and the second

14   issue is, is the limitation of a prescription

15   for a year, is a state-by-state issue.

16                 For     example,    in     the    State     of

17   Florida, it is a regulation.

18                 DR. REIDENBERG: Okay, okay.

19                 CHAIR     SEYMOUR:    Thank       you,     any

20   other questions?       Okay, sure.

21                 DR. LEONARD-SEGAL: Thank you, that

22   was a very interesting talk, lot to think




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
                                                                        Page 96
 1   about.

 2                   On    your    conclusion      slide,       about

 3   inhaled albuterol being made nonprescription

 4   as well as prescription, we have problems, in

 5   terms of the law, in terms of that.

 6                   If a product can be OTC, it must

 7   be OTC.      It's the Duram-Humphrey Act.             We

 8   can't have the same product Rx and OTC, for

 9   the same population, for the same indication.

10                 We     have    to   have    a   meaningful

11   difference between the Rx, and that's a legal

12   and medical definition between Rx and OTC.

13                  DR. REIDENBERG: Okay.

14                  DR. LEONARD-SEGAL: So, could I ask

15   you to elaborate.

16                  DR.     REIDENBERG:       Sure,   this      has

17   been done.

18                  DR. LEONARD-SEGAL: If we thought

19   we   would    be     switching     the    inhaler,     the

20   albuterol     inhaler,       to   OTC,    I   mean,    if    a

21   company came out with and wanted to make an

22   NDA, we would lose it Rx.




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
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 1                   DR.     REIDENBERG:     Okay,    this    is

 2   certainly being done with some of the non-

 3   steroid    anti-inflammatory,          where    there's    a

 4   difference in dose.

 5                   And so, I'm sure that if we were

 6   to agree that this is what's best for patient

 7   care, then we can be imaginative enough to

 8   figure out a way to do it legally, and if we

 9   really    had    to,     if   it's   really     best    for

10   patients, let's not have the law interfere

11   with what's best medically for sick people.

12                   DR.    LEONARD-SEGAL:     Unfortunately,

13   we run into this barrier all the time.

14                   DR. REIDENBERG: Well, sure.

15                   DR. LEONARD-SEGAL: The law is very

16   complicated,      and    we   always    have, what the

17   physicians think is best, is not always what

18   we're allowed to do.

19                   DR. REIDENBERG: I understand that.

20                   DR.    LEONARD-SEGAL:     So,    I     guess

21   that I would ask your opinion, knowing what

22   you've said and knowing where you're coming




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
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 1   from, if we ran into this conundrum, where we

 2   could   not   clinically         define    a    meaningful

 3   difference,       would    you    have    a    view     as   to

 4   whether the albuterol inhaler would be better

 5   OTC or Rx?

 6                 DR. REIDENBERG: I would have to

 7   have somebody knowledgeable in the economics

 8   of it, because what we're talking about now is

 9   the money, not the principle, and I don't know

10   that.

11                 On the other hand, we've solved

12   this with ibuprofen and so, if people take two

13   over-the-counter          tablets    instead       of    one

14   prescribed tablet, you get relief of pain.

15                 I    think     there   are       other    non-

16   steroidals where this has been worked out and

17   I'm just optimistic enough that if it takes

18   more puffs of the over-the-counter than the

19   prescription, to get bronchodilator effect,

20   people with asthma will take the puffs they

21   need.

22                 Les showed the data beautifully,




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                          Page 99
 1   with the inhaled epinephrine in that study

 2   that he did, and so, I recognize what the law

 3   is. I also recognize that with imagination,

 4   with the non-steroidals, people who have been

 5   able to make it both ways within the law.

 6                   I think when we're talking about

 7   changing the law, this is for those of us in

 8   the     health        care        professions      in      our

 9   organizations         to   deal      with,   certainly       a

10   federal agency isn't in a position to tell

11   Congress what it should do, but I am, and so,

12   that's the best.

13                   It's a fair question and that's

14   the best I can answer it.

15                   DR.    LEONARD-SEGAL:         I    would    make

16   one more comment regarding the end sets.                   The

17   way    the    end-sets       is    switched,      we've    got

18   Naproxen, we've got ketoprofen and we've got

19   ibuprofen      and    of     course,    aspirin has been

20   there for a very long time and has its own

21   very quirky regulatory circumstances, because

22   it's    a    monograph       ingredient      and    it    has    a




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
                                                                     Page 100
 1   strange     thing     called    professional         labeling

 2   that    covers        what     normally        would      be

 3   prescription indications for all other NSAIDS,

 4   conditions that are not self-diagnosable.

 5                  We          need          self-diagnosable

 6   conditions for a product to be OTC.                 So,

 7   aspirin goes off into strange quirks this way,

 8   in   terms    of     the   regulations because under

 9   professional        labeling,     it    has    rheumatoid

10   arthritis     indications       and     it    has    primary

11   prevention of cardiac infarct indications and

12   it has osteoarthritis indications and we don't

13   think   any    of    these     are     self-diagnosable

14   conditions by the OTC consumer.

15                  The    NSAID     indications         OTC   are

16   minor aches and pains of arthritis, back ache,

17   this thing, that thing and fever, and so, for

18   the product to go OTC, it needs to be a self-

19   diagnosable condition that a dose that would

20   be safe and effective for those conditions.

21                  Where we don't get into play is

22   the off-label use of these products and we




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
                                                                     Page 101
 1   know that physicians sometimes tell patients

 2   to use them.

 3                 I'm          a          rheumatologist       by

 4   background.       I have done this myself. I've

 5   told people to go out and buy              ibuprofen, take

 6   three, don't take one.           It's the same       you

 7   know, for people that have a hard time getting

 8   in with the prescription.

 9                 But that's not where the agency

10   can be.

11                 DR. REIDENBERG: Sure, okay.              Well,

12   let me comment because again, insulin is OTC

13   and I'm sure there's a history to that too.

14                 I    think       that    there   are   enough

15   people knowledgeable in each of the areas or

16   disciplines involved, law, medicine, whatever,

17   that if we were to decide that this would be a

18   good thing, I'm optimistic enough to think

19   that there would be a way to do within the

20   regulations as they exist.

21                 I think that we've got a major

22   issue here, with respect to the question of




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                               Page 102
 1   whether needing a refill prescription is a

 2   barrier for maintenance of chronic disease,

 3   that I just started thinking about, in the

 4   context of preparing for this talk.

 5                  But with respect to the particular

 6   issues of this meeting, if we don't have the

 7   albuterol available without a prescription,

 8   then we're going to have these people who, for

 9   whatever   reason,      tend   not   to   follow    a

10   recommended method of medical care, going to

11   less effective and toxic things that are over-

12   the-counter.

13                  And since this is the alternative

14   in reality, then I would rather work with

15   people   who    think   that   having     albuterol

16   available OTC in addition, is better for the

17   people, and then let's figure out how we can

18   do it, rather than why we can't.

19                  CHAIR SEYMOUR: I think we have a

20   couple of other questions, Dr. Hendeles.

21                  DR. REIDENBERG: Sure.

22                  CHAIR    SEYMOUR:     They've       been




                       Neal R. Gross & Co., Inc.
                              202-234-4433
                                                                        Page 103
 1   patient down there.

 2                  DR. HENDELES: I think the solution

 3   is a third category of drugs, and I realize it

 4   would take an act of Congress to make that

 5   happen,     but    if    a   patient      could    go    to    a

 6   pharmacist who could evaluate, triage that

 7   patient as to being well, that it's safe to

 8   have albuterol and could dispense it, I think

 9   it would solve both problems.

10                 It    would       provide    it     for    the

11   patient who should be treated, who can safely

12   be treated with an over-the-counter product.

13   It would also identify the patient who was in

14   need of steroids and send them to a health

15   care   provider,        maybe    even    a county health

16   department.

17                 This has been done, you know, in

18   Australia and New Zealand, there actually is a

19   provision    for    that     and    it    has     been    very

20   successful and I think there is a few other

21   countries,    where       pharmacists      are     specially

22   trained, and it's not hard to do.               They are




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                     Page 104
 1   trained. In fact, in Florida, they can give

 2   influenza vaccines, the morning after pill and

 3   things      like    that,    and   I    think   that's    the

 4   process that would identify the patient who is

 5   at risk of dying or going into respiratory

 6   failure and get that patient to medical care,

 7   and the one who could safely treat themselves,

 8   it would. And I'd be interested in hearing the

 9   agency's comment on where things are with this

10   third category of drugs.

11                  DR.     LEONARD-SEGAL:      Okay,   I     can

12   speak for myself.        I'm going to give you an

13   agency disclaimer now, because this is a very

14   complicated issue and it's come up many, many

15   times.

16                  We've        had    it    come    up      in

17   discussion.        We've had some very interesting

18   switch products that have knocked on our door,

19   that have become public knowledge, because

20   advisory committees, probably the statins are

21   the ones that would come best to my mind. Ruth

22   has   sat    on     NDAC,    our nonprescription drug




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
                                                                   Page 105
 1   advisory committee in the past.          I don't know

 2   if you can think of any others, where this has

 3   swirled to this degree.

 4                  There    are     a     lot     of     people

 5   interested in this third category.            It, to my

 6   understanding,     it   would    take    an    act    of

 7   Congress.   There are a lot of pluses to it and

 8   a lot of minuses to it, and I certainly know

 9   that it would. I doubt that we'll have it.

10               If we ever get it, I doubt that

11   we'll have it by 2011, the end of December.

12   So, that is certainly a topic for another

13   time.

14               I would also comment on the OTC

15   epinephrine.    We do not regulate that, in the

16   Office of None-Prescription Products.              It's

17   neither monograph nor NDA.          It is regulated in

18   a quirky way.    The insulin is overseen in the

19   prescription    division,     the     metabolic      and

20   endocrine division, and how it is out there

21   for diagnosed diabetics, to be able to just go

22   get it, is a quirk of regulation that I think




                       Neal R. Gross & Co., Inc.
                              202-234-4433
                                                                  Page 106
 1   you     guys   did    some    investigating    into    and

 2   probably know more than I do about it at this

 3   point.

 4                   I    know    that   it's   only    older

 5   insulin products that are available that way.

 6                   DR. REIDENBERG: Yes.

 7                   DR. LEONARD-SEGAL: I don't think

 8   the new ones are available that way.              I can't

 9   tell you why.        I can't tell you why not.        But

10   it is a quirk.

11                  DR. REIDENBERG: Okay.

12                  DR.           LEONARD-SEGAL:           It's

13   interesting, the quirks exist though, isn't

14   it?

15                  DR. REIDENBERG: Yes, particularly

16   where quirks enable the patients to get better

17   care.

18                  DR. LEONARD-SEGAL: Okay.

19                  CHAIR SEYMOUR: I think we have one

20   more question and then maybe we'll take our

21   scheduled break.       Dr. Liu?

22                  DR. LIU: Many years ago, I'm sure




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
                                                                    Page 107
 1   Les remembers this, there was a brief period

 2   of time, metoproterenol, I believe, was over-

 3   the-counter and I'm sure this debate went back

 4   and    forth,      in    terms     of,    what   are   the

 5   advantages and disadvantages and I don't know

 6   if there is insight.

 7                     I'd love to hear what the story

 8   was. Well, I can understand why it was put

 9   over-the-counter.          But then what led to the

10   withdrawal, after a fairly short period of

11   time, it was after a year or two, that it was

12   over-the-counter,          and   I    suspect    there   are

13   reasons for that as, well, because I would

14   just point out that one of the problems that

15   we    face   is    the     abuse     of   beta   agonists,

16   delaying appropriate management.

17                   DR.      REIDENBERG:      When   you   say

18   abuse, I'd like you to define that because

19   most   people,      when     they     hear   abuse,    think

20   getting high.

21                   DR. LIU: Yes, abuse means that the

22   slide that Les showed, of the number of puffs




                             Neal R. Gross & Co., Inc.
                                    202-234-4433
                                                                  Page 108
 1   that somebody takes in the 24 hours before

 2   they come into the hospital.

 3                 DR.    REIDENBERG:      Is    there   any

 4   evidence     that     this      is    OTC     and     not

 5   prescription?

 6                 DR. LIU: No, this is prescription

 7   use, but nonprescribed use of the medication,

 8   which is being taken under supervision, but

 9   would be even potentially, more of a problem,

10   if   you   made   this   drug    available     over    the

11   counter. I say potentially, but I mean, you

12   know, that's why I'm sort of interested in

13   terms of what debate took place, when the

14   exact same issue came up, with another beta

15   agonist    medication,    well,      relatively     short

16   acting beta agonist medication that went over-

17   the-counter and then what happened?

18                 Were    there   particular      sentinel

19   events that led to its withdrawal or what else

20   went on, because I think it could go either

21   way.   It could be that you're making access

22   better, or that you're actually encouraging




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                          Page 109
 1   people. You're promoting and facilitating a

 2   practice that actually leads to fatal asthma

 3   and more deaths.

 4                DR. LEONARD-SEGAL: I do not know

 5   the history of metaproterenol.     I asked Dr.

 6   Chowdhury if he did.    I don't know.

 7                I guess you have a comment.      I

 8   just want to make one additional comment on

 9   epinephrine.

10                If the CFC issue were not upon us,

11   and this were not an environmental issue, as

12   part of international and national law and

13   agreement,   epinephrine   meter   dose   inhalers

14   propelled by CFC would not be being withdrawn

15   from the OTC market.

16                I think that we need to keep that

17   in perspective.    In our division, this product

18   is regulated under the NDA process, the meter

19   dose inhaler.   It's not a monograph product,

20   it's an NDA, and we have not seen the adverse

21   event data that would have come to us, that

22   would have risen to the level where we would




                       Neal R. Gross & Co., Inc.
                              202-234-4433
                                                                          Page 110
 1   have said, "We have too many safety signals

 2   here.         We're    going         to   take   this    off   the

 3   market."

 4                      That    is     not     what   we're     talking

 5   about here today.           I just want to get us back

 6   to what we're talking about.                 We're talking

 7   about     an    ozone      depletion        issue   that     is

 8   impacting a drug, because of the way it's

 9   delivered, that is going to impact the over-

10   the-counter population of asthma patients who

11   use it.

12                   And so, I just want you to bear

13   that in mind.         Did you have a comment on the

14   other?

15                   DR.       HENDELES:       Just   briefly,      it

16   actually was only over-the-counter for a few

17   months and Dr. Badrul Chowdhury's predecessor

18   made    the    decision         on    his   own,    without

19   consulting an advisory panel, to move it over-

20   the-counter and got approval for doing it, and

21   neglected      a    body     of      literature     that    had

22   metaproterenol under a different generic name




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
                                                                       Page 111
 1   called orciprenaline, in Australia and New

 2   Zealand and there was clear data showing that

 3   the     over-the-counter          use    of    that drug was

 4   associated with increased deaths from asthma

 5   and when the Government withdrew the over-the-

 6   counter approval of orciprenaline, the number

 7   of deaths dropped.

 8                      And    so,    there    was    just   outrage

 9   among the Academy of Allergy and the American

10   Thoracic Society, that this was done and the

11   biggest    problem         is,   it     was    done   without

12   consulting an advisory panel and clearly, FDA

13   has learned their lesson from that in the

14   years to follow.

15                   DR. REIDENBERG: And just another

16   comment,      in    that     study      that    Les   showed,

17   comparing epinephrine to albuterol, you start

18   off by saying, these were college students,

19   using    it    for       relieving      nighttime     asthma,

20   whatever instruction they may or may not have

21   gotten, it worked for them, and so, it was

22   appropriate.




                              Neal R. Gross & Co., Inc.
                                     202-234-4433
                                                                     Page 112
 1                   CHAIR SEYMOUR: I think with this,

 2   we should conclude the morning first part of

 3   the session and then go ahead and take our

 4   scheduled break.

 5                   We're   a   little       behind   schedule,

 6   according to my clock.        So, if we can try and

 7   get back on schedule and resume at 10:45 a.m.,

 8   we'll take a 10 minute break.             Thank you.

 9                   (Whereupon,        the     above-entitled

10   matter went off the record at 10:36 a.m. and

11   resumed at 10:49 a.m.)

12                  CHAIR SEYMOUR: Okay, we're going

13   to move onto the next item in our agenda, and

14   we   welcome    Stephen     Campbell,      who    is    from

15   Armstrong Pharmaceuticals, who is going to

16   talk to us about the product.            Thank you very

17   much.

18                  MR.    CAMPBELL:     Thank    you,      Dr.

19   Seymour   and    actually,     I    am    representing

20   Armstrong      Pharmaceuticals,          that     is     a

21   subsidiary of Amphastar.        Good morning.

22                  We     are    the     manufacturer         and




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
                                                                             Page 113
 1   distributor of Primatene Mist and as such, we

 2   are     committed      to     keeping    an     OTC    product

 3   available and are working toward that end.

 4                    However,       the    first     thing       is    to

 5   educate the users in the event that we're not

 6   ready     in    time.         We're    hoping     that       won't

 7   happen,        but     certainly,        it's      always          a

 8   possibility.

 9                    Right now, Primatene is the only

10   approved MDI over-the-counter for temporary

11   relief    of     bronchial      asthma.         It's     a    non-

12   selective       beta    agonist       with    alpha    agonist

13   activity.         Relief      occurs     in    roughly       15

14   seconds.       It's a short acting beta, duration

15   is about 30 minutes.

16                    There's over a 50 year history of

17   the safe and effective use of this product. It

18   was    originally       introduced       under    an NDA by

19   Wyeth     Consumer          Health      Care,     based           on

20   information Wyeth provided to us, over the

21   time    they     had    the    product.         They     sold

22   approximately 183 million units, 25 billion




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
                                                                       Page 114
 1   dosing episodes and about four and a half

 2   million units sold a year.

 3                  I    only     wish    we    were     actually

 4   selling 15 or 16 million a year.                 But we're

 5   happy to have the sales we do.

 6                  We    estimate       that    it's     used    by

 7   somewhere    between       two   and      three     million

 8   consumers    every     year.         The    product     is

 9   currently available through major chain drug

10   stores, independent drug stores.              Armstrong

11   distributes,       through    the    chain       drug   store

12   distribution        centers      and      it's    currently

13   available in 45 states.          It's not available in

14   Arkansas, Montana, South Dakota and Wyoming.

15   It could be available, but apparently, the

16   demand isn't there.

17                 The top five states for shipment

18   of   the   product     are    Tennessee,         Virginia,

19   California, Texas and Florida.

20                 Again,       roughly         two     to    three

21   million users, spread all across the country.

22    Users are less likely to have medical and/or




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                  Page 115
 1   prescription drug insurance coverage, although

 2   we know that it is also used as a complement

 3   medication for those who do have prescription

 4   coverage.

 5                  It's    amazing     that    this   product,

 6   which is not actively marketed, there's no

 7   advertising campaign, but there's still demand

 8   for this product after over 50 years on the

 9   market.

10                Armstrong is committed to a smooth

11   transition and communication of the transition

12   from the CFC version, hopefully to the HFA

13   version, which we hope to have available by

14   the end of 2011, and that will depend on the

15   quality of the work we do, in presenting it to

16   Dr. Chowdhury's division and the OTC division.

17                We    believe     it's   important      to

18   provide   long    term   OTC     alternative      because

19   there are times when someone who is on a

20   prescription     med   may   not    have    an    inhaler

21   available.   They can walk into any drug store

22   and buy this product and use it and as you've




                       Neal R. Gross & Co., Inc.
                              202-234-4433
                                                                           Page 116
 1   heard, it is safe and effective, also, can

 2   help in avoiding visits to the emergency room.

 3                    We           completed            the          HFA

 4   characterization studies in 2007 and have been

 5   working on the finer details of formulation.

 6   We expected to file the IND this month.                    It

 7   will actually be next month.

 8                    The        clinical     plan       has     been

 9   reviewed      with     FDA     and   the     clinical      study

10   products      have     been    manufactured        and     QA

11   released at this point in time.

12                   What we're seeing indications of

13   is     similar        efficacy       with     the        current

14   formulation, better deliverability, possibly a

15   lower dose, so, you're actually delivering

16   less    API    and     achieving       the   same    effect,

17   because    less       API    will    lodge    in    throat       to

18   reduce the absorption side effects.                 The long

19   term stability of the product is good.

20                   We     recognize       the   importance         of

21   having an OTC medicine out there and we're

22   committed      to     develop    and     commercialize          a




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
                                                                     Page 117
 1   replacement for the CFC inhaler, but in the

 2   interim,      because       that    product     is      not

 3   available,     what    we've     done,    working     in

 4   conjunction     with    the     agency,    is alter the

 5   labeling,     both    the    package     insert and the

 6   outer carton, will very soon bear the legend

 7   that this product will not be available after

 8   December    31,   2011,      see   your physician for

 9   alternative treatments.

10                 We'll      also      be     publishing       on

11   Armstrong's website, a full page discussion of

12   the reasons for removal of this product and

13   strong recommendations that patients see a

14   physician, as I said, either county health

15   department,    private      physician,      clinic,    but

16   they see a physician to discuss alternative

17   treatments.

18                 That's what we have.          Are there

19   any questions?

20                 CHAIR SEYMOUR: Dr. Parker?

21                 DR. PARKER: A couple of questions.

22   When do you anticipate putting these things,




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
                                                             Page 118
 1   and exactly where will they be?         Will they be

 2   on the primary container?       Will they be on the

 3   outside?   Are the going to be on the insert?

 4                MR.    CAMPBELL:    FDA    has   already

 5   approved the labeling changes.         They will be

 6   on the box and on the insert.

 7                The primary label on the container

 8   is too small to accommodate the text.

 9                DR. PARKER: Do you have samples of

10   what it looks like?

11               MR. CAMPBELL: I don't have them

12   with me, but I can certainly supply them.

13               DR. PARKER: That would be great.

14               CHAIR SEYMOUR: Dr. Liu?

15               DR. LIU: You mentioned a little

16   bit of information about who was using this

17   and are there anymore details on who, because

18   by just a rough calculation, if you have two

19   to three million consumers and about four and

20   a half million units being sold, that's about

21   two per year, you know, per patient, which is

22   a reasonable number.




                        Neal R. Gross & Co., Inc.
                               202-234-4433
                                                                Page 119
 1                 I    just   wonder   if    there's     any

 2   extension of that information?

 3                 MR. CAMPBELL: We don't have any

 4   further    demographics     on   the    use   and    the

 5   previous owner of the NDA, Wyeth, didn't have

 6   it either.

 7                 CHAIR SEYMOUR: Dr. Chowdhury?

 8                 DR. CHOWDHURY: I just want to make

 9   one    comment    and   I'll   probably    pose     one

10   question, and the comment is to follow up on

11   the labeling change, stating that the product

12   will not be available in 2011.

13                This is what Armstrong has done in

14   a discussion with us and what is similar,

15   actually, a statement was also placed in the

16   albuterol, that albuterol was being phased

17   out.   This basically is following that pride

18   example.   I just want to clarify that.

19                And just a question to you, or

20   maybe a comment, and first of all, thanks for

21   being here and letting everybody know what

22   your plans are for the transition strategy.




                        Neal R. Gross & Co., Inc.
                               202-234-4433
                                                                              Page 120
 1                    I would like to have two questions

 2   to you.       First, is the fact that CFC-propelled

 3   epinephrine will be gone for the market has

 4   been known for years, a very, very long time,

 5   and      do     you     have       any        idea     with        two

 6   manufacturers being there, they Wyeth and the

 7   NDA, was NDA holder, what has happened, as far

 8   as alternate being brought to the market for

 9   the    years     that       everybody     has       known    this

10   product will be phased out?

11                    And the second thing is, the issue

12   of    cost     has    come    up    multiple         times    in

13   discussion here.         I just wanted to ask you to

14   speculate, if you can, what potentially could

15   be    the     price    of    an    epinephrine         propelled

16   agent?      Thank you.

17                    MR.    CAMPBELL:        As    to     the    first

18   question, the history of the marketing and

19   NDA, of course, Wyeth introduced this product

20   in 1956.

21                    In     2008,       we     purchased          the

22   trademark       from    Wyeth.        They      had     made    a




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
                                                                      Page 121
 1   decision not to move forward with an non-CFC

 2   product.    They determined they didn't have the

 3   capability to develop it properly, and we took

 4   advantage of that and purchased the trademark,

 5   knowing we could come up with a suitable HFA

 6   formulation, which is how we came to own the

 7   trademark last year.         And the second question?

 8                 DR. CHOWDHURY: Second question was

 9   if you could comment, again, if you can.

10                 MR. CAMPBELL: Okay.

11                 DR.    CHOWDHURY:      The    pricing       with

12   HFA   properly       being     used       in     alternate

13   production.

14                 MR.     CAMPBELL:       I     don't       have

15   detailed knowledge of what the cost will be.

16   We know it will be more expensive than the CFC

17   version,    just    because    the    HFA      is   a   more

18   expensive material.

19                 We do have a couple of things that

20   may help control that cost.          We're going out

21   of the current glass bottle, into an aluminum

22   canister.      The    product    will      still     be




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                        Page 122
 1   available. Will still, as the current product

 2   does,    contain       a    considerable     amount     of

 3   alcohol.       We haven't been able to remove that.

 4                    But we are doing all we can to

 5   maintain the price, as reasonably as possible,

 6   realizing that this product primarily serves

 7   people    who     don't      have     primary   insurance

 8   coverage.

 9                    CHAIR SEYMOUR: Dr. Parker?

10                   DR. PARKER: I was just curious,

11   whether with the new product, you continue to

12   plan to make this available only through the

13   chain drug stores, independent drugs stores

14   and without the promotion around it?

15                   I understand that Armstrong took

16   this    over    from       Wyeth,   you   know,    with      the

17   intent to feel like this was something they

18   could move forward with.            Wyeth wasn't going

19   to do it.      You all are going to do it.

20                   So, I'm sort of curious whether or

21   not, as part of the new product, there is a

22   new    strategy    to       promote    its   use   in   any




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                           Page 123
 1   different way?

 2                 MR. CAMPBELL: No, there really is

 3   not an intent to go out and broadly advertise

 4   this product.     We plan just to transition it

 5   to its current users.       We're not going to go

 6   out and push to take market share out of

 7   albuterol.    That doesn't make sense.

 8                 This is a very limited population

 9   we're serving.

10                 CHAIR SEYMOUR: Dr. Reidenberg?

11                 DR. REIDENBERG: Yes, at the time,

12   I was preparing my talk, I was unaware that

13   this was a possibility and so, in retrospect,

14   I wish I had said that we need some inhaled

15   beta   agonist,      rather    than    specifically

16   albuterol.

17                 What   have   been   some   of   the

18   barriers, that even now, you don't know that

19   it will be ready on time?

20                 MR. CAMPBELL: Formulation has been

21   an issue.    We've had to go through several

22   formulation changes, to make sure we had a




                       Neal R. Gross & Co., Inc.
                              202-234-4433
                                                                        Page 124
 1   product that would remain stable, over the

 2   long term.     That's been the primary issue.

 3   That   was    the     reason   Wyeth       decided    not     to

 4   develop it, because they couldn't do that.

 5                  We have been able to do that now

 6   and we have stability testing ongoing at the

 7   moment.    We're confident that the product will

 8   be available and if we write a good NDA, Dr.

 9   Chowdhury's group will review it in a timely

10   manner and we'll make the deadline.

11                  CHAIR SEYMOUR: Dr. Hendeles?

12                  DR.     HENDELES:       I     have     three

13   questions.     First, did you consider using a

14   breath-actuated delivery method?

15                  MR.     CAMPBELL:       Not     for     this

16   product.     We're looking at other products for

17   breath-activated, but not for this product.

18                  DR. HENDELES: Because I still have

19   concerns      about     people     being       able      to

20   effectively use it without being trained and

21   the problems with an MDI.

22                  The    second   question       I   have      is,




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
                                                                          Page 125
 1   have you performed any studies that look at

 2   the   systemic         effects   of    your    formulation,

 3   because     the    possibility        exists,      that    the

 4   reason why we found no bio-availability was

 5   because     of    the     delivery     method      and    not

 6   necessarily the drug.

 7                    I'm     aware   that      there    is    a    air

 8   epinephrine product that is being developed

 9   for anaphylaxis.

10                    MR.    CAMPBELL:     As    part    of    our

11   clinical program, we will be looking at that.

12                    DR. HENDELES: But you haven't done

13   that yet?

14                    MR.    CAMPBELL:     We    have    not       done

15   that yet.

16                    DR. HENDELES: Because that could

17   be a rate limiting step.

18                    MR. CAMPBELL: Absolutely.

19                    DR. HENDELES: And then the last

20   issue is, is it going require a foil package,

21   to prevent the effects of water egressing into

22   the canister?




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
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 1                MR. CAMPBELL: No, in this case,

 2   we're   using   an    aluminum    canister       with   an

 3   aluminum   seal,     so,   it   will   be    a     complete

 4   moisture barrier.

 5                DR. CHOWDHURY: I am Dr. Chowdhury,

 6   just taking the floor again, to respond to

 7   some comment that was made and possibly to

 8   clarify some of the issues here.

 9                One of the comments was, what was

10   the barrier for re-formulation, that I want to

11   address, and the second one is the breath-

12   actuated device.

13               Firstly, for the Montreal Protocol

14   standpoint and having worked through these re-

15   formulations in our divisions and also looking

16   at   re-formulations       globally,        with     many

17   products, one thing that I think we have come

18   to understand and realize, that just taking a

19   simple CFC out and putting in HFA is not

20   actually what happens.

21               That was the initial thought, that

22   that's the way it would happen, but actually,




                        Neal R. Gross & Co., Inc.
                               202-234-4433
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 1   it does not because the partial pressure and

 2   the physical chemical characteristics of HFA

 3   is really different than CFCs.

 4                   A typical inhaler is a component

 5   of canister formulation, metering mechanisms,

 6   valves and all of these things, and depending

 7   on the formulation and how the HFA is behaving

 8   in the formulation and how the active drug is

 9   behaving    in    the    formulation,        for    many   of

10   these, it actually has required substantial

11   changes    to    the    whole     product,    essentially

12   requiring    often,      different     valve       metering

13   chambers and actuating mechanisms in all.

14                   So,    the   re-formulation         is   often

15   very   challenging.          It    is somewhat product

16   specific    and    without      getting   into it, one

17   cannot really even speculate how complicated

18   it may become.

19                   For example, the albuterol is one

20   of the prime targets for re-formulation.                 It's

21   has taken actually many, many years, and for

22   many steroids, as you can probably appreciate,




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
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 1   has not been re-formulated.

 2                 If you think about beta agonist

 3   bronchodilators,        historically,        we    had

 4   epinephrine,        albuterol,        metaproterenol,

 5   pirbuterol, isoproterenol, about five to 10

 6   years ago, and as we are standing now, we are

 7   looking at potentially down the road, only

 8   albuterol.    Metoproterenol has not been re-

 9   formulated and I showed you the proposed rule.

10                 The pirbuterol has not been re-

11   formulated.    I showed you the proposed rule.

12                 So, it really is something that we

13   need to appreciate, that re-formulation not

14   necessarily is that simple.

15                 The    second   thing    to   understand,

16   that breath-actuated device seems attractive,

17   on the other hand, we also have to take into

18   consideration what the formulation is in the

19   product,   because     with   the   breath-actuated

20   product, most of these actually have a time

21   when the valve is open.       This is the mechanism

22   of the breath-actuated device, and with the




                         Neal R. Gross & Co., Inc.
                                202-234-4433
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 1   HFA formulation, it is not necessarily often

 2   as forgiving as CFC formulation is.

 3                    So, whether even for epinephrine,

 4   whether the breath-actuated device is visible

 5   or   not,      it's     something      that      one     should

 6   investigate.          Maybe it is, we don't know.

 7                    So, we have to understand going

 8   forward, what re-formulation does and is doing

 9   is      very     encouraging          and     we       are    very

10   enthusiastic and positive and encouraged a lot

11   about it.       But as far as the rule goes, we are

12   going    ahead     with      or    without    an       alternate

13   product.       Thank you.

14                    DR. LIU: Just a quick question.

15   Is it possible to use a dry powder formulation

16   for any of these?           Has that been explored, and

17   just eliminated?

18                    DR.     CHOWDHURY:         Actually,        dry

19   powder formulation is pretty attractive and in

20   fact, outside the U.S., it actually is often

21   preferred       and    if    you    look    at     the    patient

22   acceptance       in    the    U.S.,    historically,         for




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
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 1   reasons not necessarily very clear to all of

 2   us, that dry powder formulation has not really

 3   been accepted.

 4                   And     as     a        result,         the     re-

 5   formulation mostly actually has happened with

 6   HFA and for the re-formulation, what we're

 7   looking for, for the Montreal Protocol, is a

 8   replacement      product.           It's     not       actuated

 9   product.      It's not the same product.

10                  So,     theoretically,          a    dry       powder

11   formulation would be replacement, but it has

12   not really happened much.

13                  On     the    other      hand,      I    think

14   globally,     there     is    some      push    toward         the

15   formulation because the global warming issue

16   that has been coming up with HFA.

17                  So, it is one way to go, but has

18   not really happened much. Thank you.

19                  CHAIR SEYMOUR: Dr. Parker?

20                  DR.     PARKER:      I    really        appreciate

21   your giving us this information on the states

22   where   the    shipment       is.        I   think       it's     so




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
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 1   important to be able to begin to think about,

 2   you know, where are the volume of users, what

 3   can we actually understand and I know there's

 4   only   so   much    that's   probably really known

 5   about who actually purchases and uses.

 6                 But it's incredibly useful to know

 7   that the top five states and what they are.

 8                 I wanted to ask you first, is that

 9   a stable pattern?      Has it been the same top

10   five states over the last three to five years?

11                MR. CAMPBELL: It appears to be,

12   yes.

13                DR. PARKER: It appears to be?         And

14   in looking at those five states, is there a

15   dominant state?

16                MR. CAMPBELL: Jacob?      I'll defer

17   to my marketing.

18                DR. PARKER: Okay, that would be

19   great, thanks.     I appreciate it.

20                MR. LIAWATIDEWI: I'm Jacob.         I'm

21   the VP of Sales and Marketing.

22                Just    to   clarify,   when   we    say




                        Neal R. Gross & Co., Inc.
                               202-234-4433
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 1   distribution, that's actually distributed to

 2   the chain store distribution center.

 3               DR. PARKER: Okay.

 4               MR. LIAWATIDEWI: It's not the real

 5   pictures that you see. There are five states

 6   that we don't send to.    Doesn't mean that five

 7   states doesn't use.

 8               DR. PARKER: Very good.

 9               MR. LIAWATIDEWI: Just because they

10   are small enough, probably.

11               DR. PARKER: How about actual use?

12   Can you help us with understanding, if we

13   were to try to take a look at the country and

14   even say, here are the areas of the United

15   States where we think most users are buying

16   these things.   Can you help us with that?

17               MR.     LIAWATIDEWI:   Unfortunately,

18   just because this is over-the-counter, dose

19   information are proprietary of the chain drug

20   stores.

21               Just earlier, when the IMS health

22   data say Wal-Mart is not included, it's not




                       Neal R. Gross & Co., Inc.
                              202-234-4433
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 1   recent     IMS    health     data,     doesn't sell that

 2   data, but because Wal-Mart doesn't want to

 3   sell that proprietary data.

 4                    So, unfortunately, a lot of the

 5   chain      store,        kind     of     safeguard     this

 6   internally.       But I would say it's almost safe,

 7   if you follow the population of demographic

 8   and also, considering probably one-third of

 9   the consumers that using these products are

10   more into the poverty level.

11                    So, probably, you could kind of

12   model    your       education,         based   on    that

13   population.         That's      probably    safe, or the

14   urban area, like the New York City, that's

15   probably    one     of    the    bigger,    Chicago,    Los

16   Angeles.         So,    that's    probably safe, doing

17   that.

18                    DR.    PARKER:    So,    modeling   it,

19   looking at that, and then the other question I

20   have, at least when I've talked to patients,

21   they're very confused about the difference

22   between asthma and COPD.




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
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 1                 I hesitate because I think we have

 2   doctors who probably also are, and so, I just

 3   am curious about whether or not you all have

 4   any information.      I know you've got some on

 5   age, but not that much.       You just know who you

 6   sell it to and who buys it and sells it

 7   somewhere.

 8                 But there seems to be an interest

 9   in understanding anything we can as we plan

10   the campaign, with you all, to sort of, figure

11   out the best way to inform.

12                 Can    you   help   us   with   thinking

13   about the age of users? You know, you've given

14   us a little about geographic distribution,

15   correlating it with poverty, which is useful.

16                 But I certainly know people with

17   COPD,   who   have    been   intermittent users as

18   well, and I know that's not what's advertised

19   on the label, per say, but you know, wheezing

20   and shortness of breath or chest tightness and

21   these things are water in the common lexicon

22   for these illnesses.




                         Neal R. Gross & Co., Inc.
                                202-234-4433
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 1                  So, I'm just curious if you all

 2   have   any    insights     into,    sort       of   an    age

 3   distribution.

 4                  MR. LIAWATIDEWI: Unfortunately, we

 5   don't have that information.

 6                  CHAIR SEYMOUR: I think we should

 7   probably go ahead and move on.            Some of this

 8   additional     questions     we    may    have      for    the

 9   manufacturer, we can also bring up in the

10   roundtable discussion.

11                  So, next on the agenda, we have

12   Dr. Ruth Parker, who is going to talk to us

13   about some communication challenges.

14                  DR. PARKER: Thank you.           You know,

15   every time I do one of these FDA things, I

16   always come away from it very intrigued by

17   whatever     the   topic    it    is,    and    all      the

18   incredible background and work that goes into

19   putting      together      the     information           we're

20   presented and the discussions that are here

21   and I learn a lot.

22                  So, I appreciate the opportunity




                        Neal R. Gross & Co., Inc.
                               202-234-4433
                                                                Page 136
 1   to be a part of this and also, just to share

 2   with you a little bit, some thoughts that I

 3   have, and you know, as usual, I pick up and

 4   learn from everybody that has presented and I

 5   think at the end of the day, you know, what

 6   we're here trying to do is figure out, you

 7   know, what is good, what is right, what do we

 8   all want to be a part of, what can we agree

 9   on?

10                 We may have different reasons that

11   we're engaged, but I think at the end of the

12   day, we do all care about the health of the

13   public and we do care about our environment.

14                 And so, I think first of all, I'll

15   just say, I think it's good that we're not

16   going to be using these CFCs and that they're

17   coming off.    It sounds like the right thing to

18   do.

19                 The    hole   in   the   ozone   is   very

20   oppressive.    It's very big.      It's very bad,

21   and we've got to figure out how we're going to

22   help people who aren't able to afford and have




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                Page 137
 1   access to some of the standard of care of

 2   treatment, which is what I wish everybody had

 3   access to.

 4                  So, we've got to sort of go with

 5   what we've got and the approach that I like to

 6   think from is, this idea of health literacy,

 7   which to me, is, how do we align the reality

 8   of the demands and the complexities and all

 9   that goes with that, inside of where we are

10   today, the reality of health and health care

11   in America?

12                 How    do   we   align   that   with   the

13   skills and ability of people to understand and

14   sort of meet them where we are, and that's

15   what I want to talk about, just for the next

16   few minutes.

17                 So, I'm going to speak about this

18   health literate approach. I'm going to mention

19   to you, a framework we've been using recently

20   at the IOM, to try to think about how we

21   intervene using that, and then I'm going to

22   keep focusing in on what I think it is we've




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                       Page 138
 1   got to somehow figure out.

 2               Who is using these things?   What

 3   are the actual key messages that we need to

 4   get to people who are using them, the real

 5   ones, based on the reality of what really is.

 6               There is key messages.   What are

 7   they, and then how do we actually communicate

 8   these messages, so that we're just not a group

 9   of people who have come up with what we think

10   needs to be communicated, but we're actually

11   meeting people where they are and meeting them

12   in a voice and in a tone and with an attitude

13   that they can understand, with information

14   that they can act on and use for their health.

15               So, here is a framework that I

16   want you to think about, for just a minute

17   about, the demands, the complexity, which are

18   overwhelming.   I don't care if it's asthma and

19   the need for self-management or diabetes or

20   hyper-tension or post-MI, or all the vaccines

21   you need or whatever it is, the demands, the

22   complexities are incredibly complicated and




                     Neal R. Gross & Co., Inc.
                            202-234-4433
                                                                      Page 139
 1   the skills and the abilities of the people who

 2   need to act on them aren't always lined up,

 3   the way they need to be.

 4                     But when they are, we all approach

 5   this thing in the middle, which is,             that we

 6   understand what it is we need to know.               It's

 7   lined up with what we need to do and we're all

 8   better for it.

 9                     So, that's kind of the framework

10   that we've been talking about recently as we

11   think about how do we actually align these

12   things.     What we know is, skills and ability

13   are not well aligned with the demands and the

14   complexity of what it is we need to be doing.

15                  And    just   to   give    you    a    quick

16   snapshot of this, here is the best view that

17   we   have    of    the   health   literacy      skills      of

18   American's:       19,000   household     adults,      below

19   basic skills, 14 percent basic skills.               This

20   is where the average Medicare patient is, 22

21   percent.

22                  The headlines of the survey were,




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
                                                                    Page 140
 1   "The good news, look, we're all intermediate.

 2    The      average      falls        out   right    there."

 3   Proficient is 12 percent.

 4                   But let me show you at a closer

 5   look, what that really means.

 6                   Below basic meant that you had a

 7   67 percent probability, which most of us would

 8   call failing, if it were our kid in school.

 9   But you had a 67 percent probability that you

10   could circle the date on an appointment slip,

11   okay.

12                   For basic, 67 percent probability

13   that you could give two reasons a person with

14   no   symptoms     should      get    tested for cancer,

15   based on a clearly written pamphlet, that was

16   written    at    about    a    fourth     or   fifth   grade

17   level.

18                   Intermediate, determine what time

19   to take a prescription medicine, based on a

20   standard label, a simple label, apparently

21   simple.

22                   And     proficient,        unfortunately,




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
                                                               Page 141
 1   this is where you need to be.           This is where

 2   we all are.      To function in our health and

 3   health    care    environment,    you     need to have

 4   proficient health literacy skills. You need to

 5   be able to calculate the employee share of

 6   health insurance using a table and only 12

 7   percent of our population falls out there.

 8                 So, the report card is not really

 9   good when you get to who are we and what are

10   we really able to do, and the communication

11   challenge becomes, this is who we are.            This

12   is our country.      This is the best available

13   data, about what it is, we can understand and

14   act on.

15                 Twelve percent of our population

16   can take an employee chart and figure out how

17   much they have to pay in a co-pay for health

18   insurance, and you saw the numbers,            the rest

19   of the population and where they live.

20                 So,    the   task   is,    how    do   we

21   communicate, given who we are and what we know

22   about ourselves?




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                              Page 142
 1                 Okay, what we've done at Emory.

 2   We've got a team, and this is just a scheme,

 3   but we're using this repeatedly.         We've just

 4   used this with a very large algorithm for

 5   H1N1, that we're hoping will have very large

 6   uptake nationally, but we're trying to come up

 7   with a process that allows to get important

 8   health messages out to the people who can use

 9   them, and let me walk you through the steps of

10   what we do.

11                 The first thing we have to do is,

12   we have to get a group of people who can agree

13   on what the message is, what is the evidence.

14   You   laugh    because    you've   sat    at    those

15   meetings, like I have, where many experts come

16   together.

17                 But if I go around this table and

18   this room right now and I said, "Tell me the

19   three things that every single person needs to

20   actually    know   and   understand     about    these

21   inhalers that are coming off the market."

22                 We've   got   to   come    to    common




                        Neal R. Gross & Co., Inc.
                               202-234-4433
                                                                       Page 143
 1   agreement,       that    those     are    the   essential

 2   messages.       It's based on evidence.           I think

 3   it's also based on reality.              We have to be

 4   real about it.         That's what we love to say in

 5   Atlanta, be real.

 6                    But we have to be real.           We have

 7   to     be    cognizant    of   what      access    is,     what

 8   financial barriers and realities are.                 We have

 9   to totally be in line with what we know the

10   best        possible     medical      care      is,      for

11   bronchospastic disease, for all this under it.

12                    So, we've got to figure out what

13   these messages are and we can do that.                We

14   shouldn't have so much that we can't agree on

15   what the most important messages are, but we

16   do need that common agreement.

17                    We take that and then we turn to

18   the experts.       The experts are the people who

19   are using this thing.          It's the people who

20   walk in the drug store or go somewhere, where

21   it sounds like it's independent drug stores or

22   chain drug stores and buy these things.




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
                                                                Page 144
 1                  We   need     to    know,    with   them,

 2   whether or not they understand these messages

 3   and how we say them, so that they do.

 4                  So, this is a very key part of

 5   this, what are our messages, step one, what do

 6   we find out? I have `patient' written here.

 7   This could be consumer.           It's an over-the-

 8   counter     product,   you     know,    but    patient,

 9   consumer, whatever you want to call it, but

10   working with them, to make sure we figure out

11   how   we   actually    say    and communicate those

12   messages.

13                 Then we develop a draft, based on

14   that, of what we think the content is with the

15   input or who the real expert are and then we

16   take it and we test it.

17                 We     test     it     with     individual

18   potential users and users and we say, "What

19   does this mean?      Do you get it?        Does it mean

20   the same thing, those of us who wrote the

21   evidence think it means, to the ones who are

22   actually going to be using it," and what we do




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                Page 145
 1   is we just keep going around this circle,

 2   until we get it right, and it takes a few

 3   times around and it's doable.

 4                  You know, there's an art to it.

 5   There's some science to it but when you leave

 6   out any of these steps, what you end up with

 7   is a whole lot of evidence and a whole lot of

 8   people     never   understand    and    a   lot   of

 9   confusion.

10                 So, here it is in a schematic way,

11   if we can agree on what it is we need to be

12   saying, and it can't be paragraphs and volumes

13   and hundreds of pages.     It's got to be the

14   essential messages that you really need to

15   know, in order to approach this safely, that

16   are grounded in reality, and then we work with

17   actual people who do use this or might be

18   using this, to get it right and then, work

19   with them to figure out the best way to get it

20   to them.

21                 That's   what     we've   learned    after

22   thinking about this for about 18 or 20 years.




                        Neal R. Gross & Co., Inc.
                               202-234-4433
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 1                  We've      done   this    with   a   lot    of

 2   different     illnesses.       American    College    of

 3   Physician's Foundation has been very involved

 4   with this.     The bottom line we hear from

 5   patients over and over is, you don't have to

 6   give   me    all    the     background    and   all   the

 7   pathophysiology, the stuff I actually love,

 8   the reason I went into medicine, but you've

 9   got to tell me what it is I need to do and

10   you've got to make it real, which is really

11   important,    when     we    look   at    access    and

12   financial barriers.

13                 What can I actually do, based on

14   the reality that it is?          What are my real

15   options here?

16                 We     incorporate     photographs      where

17   ever we can.       People like pictures, that's

18   really important, diagrams, little schematics

19   are not nearly as good as real people.              People

20   are people, so they tend to like photographs a

21   whole lot better than some of the other stuff.

22                 You know, what I had as background




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                             Page 147
 1   coming to this, that it sounded like you were

 2   about    four       million      of    these      sold    a     year.

 3   There was very little data available in the

 4   literature, but it's very clear to me, these

 5   people who are buying this are the experts.

 6   They do exist and they're a bunch of them.

 7                      So, who uses them and what do we

 8   know    about       those    skills         and abilities, if

 9   we're going to align that with the far side?

10   The    hypotheses,      and      this       is from clinical

11   practice,      I    work    in     a    big,      urban    public

12   hospital.      I certainly have seen people over

13   the    years    who    use     these        and    see    people

14   occasionally        now,    who       do.      But      those    are

15   people inside the hospital.

16                   What I'm not getting are people

17   who    may   not     ever     be      inside      the    hospital.

18   There are biases where ever you are.

19                   But what I've run across and what

20   I hear from others, "Ran out of prescription

21   inhalers,"         maybe      kids,         that's       pretty

22   worrisome, given the prevalence of asthma,




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
                                                                Page 148
 1   given what we know about the epidemiology of

 2   it,   lacking     regular   care,   lacking      access,

 3   financial barriers, geographic location, I'm

 4   keenly interested in that, in knowing anything

 5   we can and does it sound like we have good

 6   information about where the real sales are,

 7   it's proprietary, but that doesn't mean it

 8   doesn't exist.

 9                   So, it might become a priority, to

10   find out as much as we can about, where are

11   the nested populations of users?          Are they

12   actually    distributed      across      our    country

13   completely equally?

14                It doesn't sound like it.           We just

15   got a list of some states that don't even want

16   it, because there's no market demand.

17                So, there is something going on in

18   those places, where this is not happening.            It

19   sounds   like    the   cities.      It    sounds    like

20   poverty, but what else can we actually find

21   out that can help us?

22                Is    language,     lack    of    primary




                        Neal R. Gross & Co., Inc.
                               202-234-4433
                                                                 Page 149
 1   English, or immigration status a barrier for

 2   presentation     to    care,   with    some   who    have

 3   bronchospastic      disease?      Is    that a target

 4   population for our messages?          Is there any way

 5   we can find out more, based on the proprietary

 6   data that does exist, about where these things

 7   are actually being purchased?

 8                 Well, I went to the drug store. I

 9   love doing this.       I like labels and I like to

10   go to the drug store.       I like to keep it real.

11    I fit in in Atlanta, because we sing about it

12   in our music down there a lot, in good and bad

13   ways, I guess, if you watch the news.

14                 Anyway, so, I did make a few calls

15   to pharmacies.      This is very limited.       This is

16   Atlanta.   That's where I live.         So, I made a

17   few   calls   and     worked   with    some   of    my

18   colleagues to make a few more, and then I made

19   a couple of trips to the drug store.

20                 So, let me tell you what I saw,

21   and you know, one way to find out would be for

22   all of us to go do this a little bit more. Go




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                   Page 150
 1   the drug store.       Talk to the pharmacist, where

 2   ever you are, and just see what's going on in

 3   the real world.

 4                 Well, this is a slide actually,

 5   that I got from a dear colleague who is in the

 6   room here, a few years ago, because I love the

 7   slide.

 8                 But     in    2001,     there   were     over

 9   300,000 OTC products available on the market.

10    So, first of all, there's a lot of stuff out

11   there in the drug store and I actually now

12   take residents and medical students and do a

13   class in the drug store.            It's one of my

14   favorite things that I actually teach.               You

15   can   learn   a   lot      in   a    drug   store,    and

16   particularly, when you start interviewing the

17   people who are in the drug store and talking

18   to them about what they're buying and why.

19                 Okay.     So, I went to the drug

20   store, just a couple of days ago.             Lo and

21   behold, right under cold and flu remedies.

22   Well, this was kind of hot for me, because




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                      Page 151
 1   like most people, I've been spending a lot of

 2   time dealing with the flu lately, with H1N1,

 3   and lo and behold, right under cold and flu

 4   remedies, sitting on the bottom shelf here, is

 5   where I found this product.

 6                   That    made      me   a   little    nervous

 7   because a lot of the work I've been doing on

 8   the flu is about how we inform the public,

 9   that one of the keenest concerns we have as

10   medical practitioners is respiratory illness

11   that    comes    on    top   of    it,     be   it   a   viral

12   pneumonia, be it a bacterial pneumonia, be it

13   respiratory distress, and how do we actually

14   get    people    to    begin   to      think    about    their

15   respiratory symptoms if they have the flu so

16   that they can know whether they need to stay

17   home and take care of themselves, call their

18   doctor or go to the emergency room, could they

19   have something?

20                   So, I got kind of nervous just

21   thinking about all the flu we're going to

22   have, and oh my gosh, here on the bottom, you




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
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 1   know, there's this thing about, you know, your

 2   asthma.

 3               So,    anyway,     that's   where   it's

 4   sitting in the drug store I visited and on the

 5   shelf, these are the pictures I've got and the

 6   little products that I ended up buying, just

 7   so I would actually know what they looked

 8   like.

 9               These two were behind the counter

10   and actually, I don't even think they had to

11   be, because they're combo.      These both have

12   the guaifenesin in them and if you're going to

13   make the bad stuff, you have to take that out.

14              So,     actually,    only    the   single

15   ingredient, technically I think, has to be

16   behind the counter.

17              But anyway, the combo ones were

18   behind the counter and I did go and buy the

19   cheapest ones of them, so, anybody who wants

20   to see them, can actually look at them and you

21   probably won't be able to read the drug facts.

22   Those are so microscopic, it's hard to read,




                       Neal R. Gross & Co., Inc.
                              202-234-4433
                                                         Page 153
 1   but they did, indeed, take my driver's license

 2   and they you know, put on here electronically,

 3   exactly how much I purchased and how much I

 4   could purchase and all of that.

 5                  When I bought it, it was about $23

 6   and the refill for it, which was also sitting

 7   available over-the-counter, was $19, $18.97,

 8   something like that.

 9                  So, if you actually want to see

10   it, I know we have slides of it.    Here it is,

11   and you can look at what it actually says. I

12   was trying to think, who might be in here and

13   who might buy it?

14                Okay, so, here is what they looked

15   like.   I've got them here, anybody who wants

16   to see them.

17                In the drug facts label, for this,

18   "For temporary relief of occasional symptoms

19   of mild asthma, wheezing, tightness of chest,"

20   tightness of chest, "Shortness of breath," I

21   think    tightness    of   chest   was   matching

22   shortness of breath.




                       Neal R. Gross & Co., Inc.
                              202-234-4433
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 1                  But     anyway,    whatever    that    is.

 2   Okay, so, these are the people that see this

 3   and say, "Well, maybe me.            I've had some

 4   symptoms."     I know that there was supposedly,

 5   something that said that you had to have been

 6   diagnosed with asthma in the past by a doctor,

 7   and I found that.          It's somewhere on one of

 8   these labels.       It's not on the primary one,

 9   but it does exist somewhere.

10                  But there is suppose to be this

11   thing, that you were told somewhere, you've

12   had asthma.     I say this because this really

13   came up when I started talking to patients,

14   and I was able to actually locate more people

15   who were elderly, with COPD, who has purchased

16   this episodically, but that means nothing.

17   I'm   just    one    person,     asking   a   lot    of

18   questions.

19                  Okay,       directions,     "adults        and

20   children     four    and    over."      So,   the    target

21   population, you know, if we're looking for who

22   we're going to be communicating with, this




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
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 1   product   has    been       available    to    adults    and

 2   children that are four and over.

 3                  Okay, so, yes, I mean, it's been

 4   out there and it says on the label that you

 5   could be four and older and use it.

 6                  So,     it    doesn't    sound     like   it's

 7   children under the age of four that it was

 8   ever even recommended for.

 9                  So, I'm trying to again, get at

10   who the users might actually be.

11                 So,       I      started        asking     the

12   pharmacist,     made    some    calls,     "Do you have

13   these OTC inhalers?         Who uses them?"       Here is

14   what I found out.

15                 "We don't have any.          I think it's

16   been discontinued."         I heard that four times.

17   That's kind of interesting.             Two of them had

18   them on the shelves, okay, but the pharmacists

19   in the back said that they had already been

20   discontinued     and    they    said,     "Yes,    they're

21   gone."

22                 Then another one, "It's going to




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
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 1   be discontinued.       People just get addicted to

 2   them."     What do you tell people about them?           I

 3   tell them to talk to the doctor, okay.            Do you

 4   have them?     Yes.    Do you see people using

 5   them?       Just   kids   who   buy    them    for   other

 6   reasons.     You mean abuse?     Yes.    They're

 7   mostly under 18?       Oh yes, other than that,

 8   just    some   people,    who   if    they    lost   their

 9   albuterol inhaler, may come and get it.

10                  So, kind of, you know, a little

11   scattered here.       How about this one?      Do you

12   have the inhalers and who uses them?           Yes, we

13   have them, but I usually try to reach their

14   doctor for a refill of their regular asthma

15   inhaler.    If we can't reach their doctor, our

16   store policy, this is a large chain drug store

17   that said this to me, is to give out one

18   emergency refill, if they have a prescription

19   on file from anywhere in the past.

20                  So, then I go. In Atlanta, we've

21   got a lot of drug stores.       I'm sure anybody

22   else from a big city does too.




                        Neal R. Gross & Co., Inc.
                               202-234-4433
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 1                 So, I go, you know, a quarter mile

 2   down the street, they don't have that policy.

 3    You can't get it there.

 4                 So, then I went to another one,

 5   quarter mile away, they didn't have it.          Then

 6   I went to another one and they said I had to

 7   call back, that the person who would know

 8   whether or not that was one of their policies,

 9   wasn't going to be there for two days.

10                 So, I was trying to think, you

11   know, if I'm somebody and I'm short of breath

12   and I might have had a prescription, you know,

13   what would I actually do?        One thing I might

14   do is checking out different pharmacies.          You

15   know,   I   might    get    something,   you   know,    a

16   quarter mile down the road, you know, based on

17   who the pharmacy is and this was just within

18   one state, and we have a lot of people who

19   live on borders and we have a lot of people

20   going to different kinds of health centers.

21                 So, I just kept trying to say,

22   we'll what is real?        What's really going on




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                           Page 158
 1   and how can we use what we're able to find

 2   out, to figure out what it is we need to say

 3   here?

 4                  So, we've got some work to do, but

 5   we've got people from different vantage points

 6   that can help us think about that.

 7                  I do think that    pharmacists can

 8   help inform us, because I do think they're

 9   getting some of the questions, although it was

10   clear to me that they said that a lot of it

11   just    goes   up   front   because   these   other

12   products are behind the counter, so they don't

13   end up interacting in the back of the store

14   with the pharmacists.

15                  The key message is, this is really

16   important.     We really need to come to some

17   kind of agreement on what the actual messages

18   are, because if we try to communicate too

19   much, we'll confuse people, and there's always

20   an ability to refer people to sites that can

21   give you more detailed information, that can

22   take this down layer upon layer, but it's




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                            Page 159
 1   really important, that we come up with the

 2   most essential messages and figure out how

 3   we're going to say them.

 4                 My   encouragement   would   be   that

 5   they're clear.     They're understandable and

 6   they're actionable.     They're not hollow bits

 7   of information that you can't do anything with

 8   on the far side.

 9                 All right, here is some possible

10   ones.   So, I took a stab here, down here at

11   the bottom.    These inhalers will not be sold

12   after December 2011.     To me, that's pretty

13   clear cut, but you know, from what I've heard,

14   I think that's accurate, they will not be sold

15   and so you need to be aware of this.

16                 I added COPD. I kept hearing from

17   different folks, that COPD patients are using

18   this.   I know it's not there, but these may be

19   some of our users.

20                 But if you have asthma, COPD or

21   you're wheezing or having trouble breathing,

22   you need to see a doctor.     That's actually a




                        Neal R. Gross & Co., Inc.
                               202-234-4433
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 1   reality,     in      our    country,       given     what's

 2   available over-the-counter and what isn't.

 3                  But    if   you're      having   trouble

 4   breathing and you've got asthma or COPD, I

 5   think the current system of care, being what

 6   it is, these are not diseases that we have

 7   deemed should be self-managed without the care

 8   of a medical provider and I think we need to

 9   make sure that everyone in the public knows

10   that.

11                 So, I took a stab.         These are

12   straw.    You can destroy them all you want, but

13   I actually think that's a very important thing

14   to know and understand.

15                 My      personal      opinion     is    that

16   particularly       parents,      I'm     boarded     in

17   pediatrics and in internal medicine, but I

18   think parents want to be good parents. Poverty

19   doesn't mean you don't want to be a good

20   parent.    A lot of times, it means that you may

21   not be clear on what it is you need to do to

22   be a good parent.       That we can help with.        You




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
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 1   need to get to a doctor.

 2                Access is a bigger issue.    I mean,

 3   that's a piece of health reform in our country

 4   right now and it's wonderful, as we look at

 5   all issues that we're addressing right now,

 6   and to think about how we make this real, as

 7   we look at who we want to be as we reform our

 8   health care system.

 9                But I think in our country, and I

10   think it's good medical practice, that asthma

11   and COPD are not diseases that you manage

12   without oversight of a medical profession.

13                So,     I   think   that's   a    very

14   important message and one that everybody needs

15   to know.   That's the best we have to offer.

16   We have access issues.     We have costs issues

17   and we're going to have to figure out the best

18   way to go at those, but you need to make sure

19   that you understand that these are diseases,

20   that you don't self-manage, without the care

21   of a medical provider.

22                Bottom line, the best medicines to




                        Neal R. Gross & Co., Inc.
                               202-234-4433
                                                       Page 162
 1   treat asthma and COPD need a prescription, the

 2   best I can tell. You can't get them without

 3   them.   You know, there are a few little stock

 4   gap things here and there, but the best ones

 5   C- and if you're looking to get the best one,

 6   then it becomes an access thing and you know,

 7   that's an issue not to ignore and it's one for

 8   us to all be cognizant of and to figure out

 9   the reality of where we can actually advise

10   people to go, and to be supportive of those

11   being available to people.

12                But these are the three messages

13   that I came up with, off the top of my head,

14   and I know the more that we give you, that's

15   specific, the more you have to begin to work

16   with.   So, I threw them out there.   Those are

17   points for further discussion.

18                This is not necessarily the exact

19   language they would be in.   Like I said, you

20   start with, what are the messages, then you

21   take these messages and you work the messages

22   with the people who might be able to use them,




                     Neal R. Gross & Co., Inc.
                            202-234-4433
                                                                 Page 163
 1   to make sure that they are said in a way that

 2   they understand, probably with a couple of

 3   photographs, that make good sense to then, not

 4   just to us, who took the photographs, but to

 5   them.

 6                       Then we take it back, because it's

 7   been reworked and we make sure we didn't lose

 8   the essence of the message, and then we figure

 9   out     how    we're     going    to   disseminate   that

10   message and a lot of that would come from

11   focus group work with actual users of the

12   drug, to find out where they would best get

13   them.

14                    Do they want them on the radio?

15   Do they want them there in the drug stores

16   where they purchase it?            Do they want it

17   brought into their home in another type of

18   medium?

19                    But it's probably not going to be

20   on an obscure website.            That can be for the

21   volumes       and    scads   of    detailed   reference

22   material, but that's not where most people are




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
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 1   living every day.

 2                   Cell      phones    may   be    a    better

 3   source, but our ability to get great messages

 4   out in a health context on that, are certainly

 5   on the horizon, but they're not here right

 6   now, but I think by 2011, that may be a better

 7   option than we think.            We know cell phone use

 8   is    much    higher      than    internet     use    and

 9   delivering good messages through that might be

10   another medium that we could explore.

11                   But we can find out, by talking to

12   the people who are actually purchasing these.

13                   So,    there     you   go,     skills     and

14   abilities and trying to align those with the

15   actual demands and complexity, and the demands

16   and complexity and the skills and abilities

17   all sit inside the reality of who we are and

18   what we have to deal with, in terms of the

19   resources and access.

20                   So, my final comment is just that

21   the   patients,       the    consumers    are       the   real

22   experts      here   and     we're   going      to    have   to




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
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 1   partner with them, as we figure out the best

 2   way to really get this message out.            That's

 3   harder to do and the step that's so often left

 4   out in so much of our communication.            We do a

 5   much better job, I think, of determining what

 6   the messages are and even getting them out.

 7                But     if    we   don't   work    with    the

 8   person who really needs them and the person

 9   who understands it the most, because that's

10   where they live and that's what they're doing,

11   then we really miss a golden opportunity to be

12   a part of real communication, which is just as

13   much about listening and understanding, as it

14   is about what we put out.

15                In    fact,    the   hardest      part    of

16   communication is listening and understanding.

17                Okay, thanks for your time.

18                CHAIR    SEYMOUR:     Thank    you,      Dr.

19   Parker.   Do we have any clarifying questions?

20               Okay, the last presentation this

21   morning is Ellen Frank from the Office of

22   Communications at the FDA.




                        Neal R. Gross & Co., Inc.
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 1                   MS. FRANK: Good morning.                My name

 2   is Ellen Frank.         I'm the Director of the

 3   Division of Public Affairs in the Center for

 4   Drug    Evaluation          and    Research,      and    this

 5   morning, I'm going to talk to you in general,

 6   about    what     we    in     the    Division      of    Public

 7   Affairs do when we decided to do education and

 8   outreach on a specific subject, and then I

 9   want to talk a little more specifically about

10   options and things that we might do, based on

11   the message and the goals that we want to get

12   out, in educating those consumers about the

13   epinephrine CFC inhaler phase-out.

14                   So, I want to begin by just in

15   general,    sharing         with     you,   the    kinds     of

16   education that we do in our division and in

17   CDER.

18                   These are typical of some of the

19   subjects    that       we    would     cover,     and    I   have

20   albuterol    up    on       top    there    because      that's

21   relevant to this and we have done education on

22   that, and I'll share some of the things we




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
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 1   have done on that, in a few minutes.

 2                      But most of our subjects, as you

 3   can    see,    are       broad.        They      reach    a    large

 4   audience.      They go nation-wide and we decide

 5   which subjects to do education on, based on a

 6   variety of ways.

 7                      Sometimes, Congress will come to

 8   us     and   say,     "Educate       on specifically, for

 9   example, generic drugs."               Other times, within

10   CDER    or    FDA,    we'll        decide,      "This     is    an

11   important message.            We need to get this out,"

12   and sometimes outside groups, organizations

13   will come to us and say, "There is something

14   important      that      we    think      FDA    could     make      a

15   difference, if they can get a message out."

16                   So, that's kind of how we make a

17   decision      on    what      to    put    our    efforts       and

18   resources in in terms of getting information

19   out to consumers.

20                   Now,       we       realized       that        the

21   epinephrine        CFC    inhaler      phase-out         is    an

22   important message to those who are using the




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
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 1   product.      But it is a narrow audience.

 2                    But     to    that    audience,         it's    an

 3   important message.            But broad, throughout the

 4   nation we may not want to do the same reach

 5   that     we   might      do    on    some    of    these       other

 6   campaigns.

 7                    So,     I    want    to    put    that     in

 8   perspective.          If we can target the audience

 9   and     reach    those       who    are    in    need     of    this

10   message, that's probably the best for us to go

11   about this education campaign because we're

12   going to be limited in resources and we're not

13   going to be able to do something that involves

14   a lot of funding and a lot of money.

15                    But I will mention now and I'll

16   mention at the end, that one of the ways we

17   really get our message out is through working

18   together with partners, and I'm hoping that

19   those    of     you    here    will       work    with    us     in

20   developing       an    education      campaign       on    this

21   subject that will get the message out.

22                    When we decide we're going to do




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
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 1   an education campaign, we usually look at the

 2   following; we decide what is our goal and then

 3   as Dr. Parker mentioned, we have to identify

 4   the   audience,        the     message,       what    education

 5   materials        we     want        to     produce,       what

 6   dissemination channels we're going to use and

 7   then evaluation.

 8                    We    have       always    been     a   little

 9   limited     on    what       we    can   do     in   terms   of

10   evaluation.       So, one way we have made an

11   effort to determine if we're even making a

12   difference, is at least to measure reach, how

13   many people are we reaching?               Are we getting

14   to the right folks?           Is the audience getting

15   the message?

16                    We can't always go back and do

17   what's involved in an evaluation, because we

18   don't have the resources.

19                    But    as    Dr.    Parker      mentioned,       I

20   think there is a way maybe to get to the

21   consumers    who       are    using      this    product     and

22   evaluate whether or not they understood the




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
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 1   message and if we even have the right message.

 2                   When we decide what products we're

 3   going to develop, we look at a broad array of

 4   options and now, this is a list of products

 5   that    we    would    develop    for   a   nationwide

 6   campaign.

 7                   For example, we might decide to a

 8   radio announcement, a public service ad that

 9   might go into newspapers and magazines.

10                  We have an exhibit program.          We'll

11   go out to various conferences and reach our

12   audiences that way.

13                  We have articles for consumers and

14   professionals, fact sheets, brochures.             We

15   reach   out    to     stakeholders,     question    and

16   answers on our website.          We even have gone to

17   the extent of putting ads on mass transit in

18   malls, buses, trains.

19                  We have internet banners that will

20   take the consumer back to our website, where

21   there's a wealth of information and we have

22   now, moving into some more of the social media




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
                                                                      Page 171
 1   like, YouTube, podcasts and we have some video

 2   news clips that have been done on some of our

 3   subjects.   We do those in-house and those go

 4   out to thousands of subscribers.

 5                So, this would be generally, our

 6   list, our menu of what we would pick from,

 7   when we're deciding what to do, in terms of

 8   developing products for our major campaigns.

 9                This       is   some    examples    now,      I'm

10   going to show you, of what we've done for some

11   of our other campaigns.

12                This is what is now called the FDA

13   consumer update.     This used to be the FDA

14   consumer magazine.       It was a hard copy.         Now,

15   it's gone to just being on the web.             But this

16   is still a wonderful resource and any time we

17   have a message, we usually try to do an FDA

18   consumer update and get that posted on the

19   web.

20                An     example         of   our     aspirin

21   campaign,   we    did    a   fact     sheet,    we   did    a

22   brochure, we did a public service ad.             That's




                       Neal R. Gross & Co., Inc.
                              202-234-4433
                                                                       Page 172
 1   typical of what we do for a national campaign.

 2                   Now,    a   lot      of    these    products,

 3   again, we don't have funding for placement of

 4   a public service ad.           So, that's why it's

 5   called public service.           We, you know, kind of,

 6   are at the mercy of a magazine or newspaper or

 7   a TV station, or whatever, to put our message

 8   out there, free of charge and sometimes, we're

 9   successful.        We'll       get     remnant space, but

10   sometimes, it is hard to get that message out

11   in that way.

12                 Brochures, we've had some success

13   in   terms   of    getting       our      brochures    in

14   pharmacies.            We'll      give       them     out    at

15   conferences and we have a lot of requests for

16   our brochures that come in and we disseminate

17   them that way.

18                 We also come up with banner ads,

19   and the nice thing about these banner ads is

20   if some of these popular websites, for example

21   here, Mapquest put up our banner ad, that

22   would   drive     folks     to    our      material    on   our




                        Neal R. Gross & Co., Inc.
                               202-234-4433
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 1   website about driving and taking medications

 2   and they did this for no cost.

 3                 So,    perhaps    there's     a    way   of

 4   getting information about this subject, the

 5   epinephrine    inhalers,    onto     those      websites

 6   where the consumers who are using them might

 7   then be able to click and get back to FDA's

 8   website for more information.         That's kind of

 9   the concept of this.

10                 This is an example of our website.

11   Everything     we    develop,   we   post       on   our

12   website.   That's where it all sits and is

13   there, but we're not always sure people are

14   going to go to the website.

15                 So, we have to come up with a

16   variety of dissemination channels.           We can't

17   just depend on everybody going to the website.

18   But there is where all of our materials will

19   exist.

20                 This is an example of the patients

21   safety news videos that I mentioned earlier.

22   They are now producing what they call patient




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                    Page 174
 1   safety news for consumers.

 2                   It was originally geared at just

 3   health professionals.          They're now doing both,

 4   one    for    consumers      and    one   for    health

 5   professionals.

 6                   This    is    a    wonderful     opportunity

 7   for us to take a message like this one, and

 8   get it on a video and they send it out to

 9   72,000 subscribers.          They put it on YouTube.

10   So, that's a possibility.

11                  In terms of dissemination, again,

12   this is a general menu of things we would

13   choose from.     I'm not saying everything on

14   here is what we would do for this education

15   campaign.     But it's a good start.

16                  We can look through this list and

17   we    could   decide,     would     going   to    certain

18   exhibits be a good place to get this message

19   out?   Maybe radio is too broad or major TV is

20   too broad.     Our audience is narrow.           That

21   wouldn't make sense.

22                  So, what would make sense?           Health




                        Neal R. Gross & Co., Inc.
                               202-234-4433
                                                           Page 175
 1   professional    conferences,      sending   letters

 2   out, doing a point of purchase.      It's a little

 3   tricky   with   point   of   purchase because the

 4   consumer of this product, probably wouldn't be

 5   going to the pharmacy counter.

 6                Would it be best, maybe, to put a

 7   shelf-talk or a little sticker on the shelf,

 8   underneath the product so when the consumer

 9   goes there now, to buy that product, they can

10   learn about what's going to be happening and

11   we can put our messages on that?     Maybe that's

12   a better way to go than having something at

13   the pharmacy counter.

14               The media is a wonderful resource

15   for us, both the mainstream and the trade

16   press and any opportunities we have to use the

17   media to get our message out, we will use

18   them.

19               Then, of course, our partnership

20   vehicles, using those organizations that have

21   the same interest and that their constituents

22   have the same interest in getting and learning




                      Neal R. Gross & Co., Inc.
                             202-234-4433
                                                                     Page 176
 1   about this subject, would be the partners we'd

 2   want to work with.

 3                 Some   examples      of     dissemination

 4   we've used, just to give you an idea of the

 5   broad aspect here, and again, this may not be

 6   appropriate for this message, but maybe it

 7   will get us thinking in the right direction.

 8                 This is an example of a generic

 9   drug   poster   that   we    have       in    pharmacies.

10   Again, this is at the pharmacy counter, may

11   not be the right place where we want to put a

12   message for this subject, but maybe it is, and

13   that's something I think we need to talk about

14   when we decide on dissemination.

15                 Magazines,      I     think        that     the

16   Parenting and Good Housekeeping are              possibly

17   too general for this subject, but there are

18   smaller   magazines,   that       ones       that   are   at

19   RiteAid and the Prevention magazine, maybe

20   that is an appropriate place.

21                 We don't have funding to place ads

22   in   these   magazines,     but    we    can     develop    a




                      Neal R. Gross & Co., Inc.
                             202-234-4433
                                                                Page 177
 1   public service message and possibly, maybe

 2   these magazines will put it in there.           So,

 3   that's an option.

 4               We    do     send     out       nationwide

 5   newspaper articles.     This might be too broad

 6   for this subject, but I think maybe there's a

 7   way to target these newspaper articles, to

 8   those states possibly, where we know there's

 9   more use of this product.       Maybe that's one

10   option.

11              For the albuterol CFC phase-out,

12   this is a list of what we did for that, in

13   educating the public.

14              We    did   Q&As     for   the    consumers.

15   They're on our website, both in English and

16   Spanish, an audio podcast, presentations.             We

17   did articles in journals, a press release and

18   a press release is very valuable.

19              When FDA puts out a press release,

20   it's picked up by the media.       So, that's an

21   excellent resource for us to get the message

22   out.




                      Neal R. Gross & Co., Inc.
                             202-234-4433
                                                                   Page 178
 1                  Patient safety news videos, we did

 2   one,   and    those    are   on   our    website     now.

 3   Letters      to    schools,    pharmacists,        public

 4   service ads and stakeholder letters and calls

 5   and of course, information on our website.

 6                  This was all done, and we might

 7   want to look at this as an example of what can

 8   we take from this and do for the epinephrine

 9   CDC inhaler phase-out.

10                  These are three examples of the

11   articles that we prepared for the albuterol

12   education program and these were picked up

13   news letters, organizations use them on their

14   website.     They're on our website.         They were

15   also used when patients would pick up their

16   prescription      at   the   pharmacy.        A    lot   of

17   pharmacies would attach this information to

18   that prescription.

19                  Another    example,      as   I    mentioned

20   before, is our website and of course it's a

21   valuable resource for us and it's where we

22   would put all of our information.




                        Neal R. Gross & Co., Inc.
                               202-234-4433
                                                                        Page 179
 1                    We    talked    earlier,    Dr.       Parker

 2   mentioned       specifically,      about    some       of    the

 3   challenges in educating consumers about the

 4   epinephrine       CFC    inhaler    phase-out,         and    I

 5   wanted     to    give    you    those    challenges,         in

 6   reference to what we did with albuterol and

 7   why this is a little bit different and this

 8   might be a little more difficult.

 9                    We mentioned, and several of us

10   mentioned, the audience.           I think after this

11   meeting,    I    know,     at   least,     have    a    little

12   better feeling of who the audience is, based

13   on Mr. Campbell's presentation and you did

14   give us some good information on who the users

15   are, where they might be located, and that's

16   going to be very helpful in us developing our

17   campaign.

18                   But the challenge is going to be,

19   what specifically about that audience do we

20   need to know?         What is their education level?

21   Where do they get their information?                How

22   will they best receive this information?                    So,




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
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 1   there is still a lot of questions that need to

 2   be answered there.

 3                 This      product,     unlike        the

 4   albuterol,    is   bought    over-the-counter,      so,

 5   we're   not   going    to   necessarily    get    that

 6   consumer to the pharmacy counter, maybe to ask

 7   the   pharmacist     some   additional    questions.

 8   It's also not a prescription, so they may not

 9   be face-to-face with their doctors, to ask

10   more questions and to be educated.        So, those

11   are some challenges.

12                 What are the alternatives?         We're

13   not sure what message we want to put out on

14   that, and then the audience, as I mentioned,

15   what should the messages be, and the audience

16   might not get all their information from the

17   website.

18                 If it's an audience that doesn't

19   have computers, maybe the website isn't going

20   to be the best place.       So, what dissemination

21   channels?

22                 So, there are some challenges here




                        Neal R. Gross & Co., Inc.
                               202-234-4433
                                                                  Page 181
 1   and I think we need to really brain-storm and

 2   identify    the      audience,     the      goals,     the

 3   messages, come to consensus as to what our

 4   messages would be, before we even begin.

 5                But we have begun and here are a

 6   few things that we've already have done, and

 7   on top of this line is we've already done.

 8   Underneath the line is some proposed options

 9   for what we can do.

10                We have consumer Q&As in English

11   and Spanish, currently on our website.          We

12   have an audio podcast of those Q&As on our

13   website.   We have presentations that have been

14   given at professional and consumer conferences

15   and this workshop is a good start.

16                Some    things   we    might    consider,

17   patient safety news videos, as I mentioned

18   before, they're now doing them for consumers.

19   So, this would be an excellent vehicle.              FDA

20   consumer   update,    which   I    showed, that's a

21   pretty easy way for us to get information out.

22   Letters to schools, letters to pharmacists,




                       Neal R. Gross & Co., Inc.
                              202-234-4433
                                                                    Page 182
 1   public     service      announcements     that    we    can

 2   prepare for news letters, send out to national

 3   organizations, to some of the partners here,

 4   who might be able to work with us on that and

 5   we can develop these products together, and

 6   then stakeholder letters and calls and, of

 7   course, our website.

 8                    So, this is kind of, what we're

 9   thinking,        the     direction      we're     possibly

10   thinking    of    going.        But    we're    not    sure.

11   That's what this workshop is            hopefully going

12   to help us with, to identify that we're on the

13   right track.

14                 Again, I mentioned, most of our

15   education campaigns that I showed on my first

16   list   have   been       done   in    partnership      with

17   outside organizations and the beauty of that

18   is that the dissemination gets so much further

19   reach when you're working with partners.

20                 There is just so much we could do

21   with the resources we have to get materials

22   printed and to reach out nationwide.




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
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 1                 So, the effect of working together

 2   is just tremendous and I want to emphasis that

 3   anybody in this room who is interested, we're

 4   interested in working together and anybody who

 5   you think isn't present today that would be

 6   interested in working on getting this message

 7   out, we're interested in that as well, and

 8   that's my conclusion.

 9                 Any information, if you'd like to

10   talk to me further, my e-mail address and my

11   phone   number,   please,    don't    hesitate    to

12   contact me.    Thank you.

13                 CHAIR SEYMOUR: Thank you, Ellen.

14   Are there any questions?

15                 MR. BRENNAN: Hi, I'm Ross Brennan

16   and as somebody who is at EPA, we've been very

17   interested     and    obviously,     following    the

18   transitions, most recently for albuterol and

19   of course, now for epinephrine.

20                 We were very appreciative of the

21   partnership    and   the   effort    undertaken    on

22   communication for the albuterol CFC inhaler




                       Neal R. Gross & Co., Inc.
                              202-234-4433
                                                                    Page 184
 1   phase-out and you characterize it as really,

 2   kind of a saturation approach, using every

 3   available technique, which was terrific and

 4   successful, from what we can tell.

 5                  I'm     wondering        if    there     were

 6   lessons      learned        from   that      particular

 7   communications approach for albuterol, that

 8   you would apply to epi?

 9                  In other words, particular venues

10   that worked or did not work, or ways that you

11   might   change     your     approach,     based on what

12   you've learned from the albuterol transition?

13                 DR. LEONARD-SEGAL: I want to say

14   that Cindi Fitzpatrick, who is in our audience

15   now, was the key project leader in doing the

16   education on the albuterol and I'd like to ask

17   Cindi   if   you     have    any   feedback    on     the

18   education we did on albuterol and what you

19   think we might have learned from that.

20                 You have to come up here, Cindi.

21                 MS. FITZPATRICK: I'm not so sure

22   that there's that much to be learned from it,




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
                                                                     Page 185
 1   because again, there were differences.                The

 2   albuterol   is      a     prescription      product,    the

 3   replacement prescription product.

 4                  We    probably       could    reach    people

 5   through the internet.            We could possibly reach

 6   people through their health care professional,

 7   their   pharmacist         and    their   physician     and

 8   through going to exhibits and telling health

 9   care professional groups about the transition

10   and how they could access materials for their

11   patients.

12                So, that was part of the reason of

13   showing the difference between albuterol and

14   epinephrine,     that      they    really    are     unique

15   challenges because we can't necessarily reach

16   them in the same manner.

17                I      don't    know    that    we    learned

18   lessons, other than that.

19                CHAIR SEYMOUR: Dr. Segal?

20                DR.        LEONARD-SEGAL:        Yes,      after

21   listening   to      Dr.    Reidenberg's      talk,     I'm

22   wondering if we should be putting up posters




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                       Page 186
 1   in homeless shelters and looking for other

 2   venues, where people that are in dire economic

 3   straits, might be spending time.

 4                  I'm     wondering          about     grocery

 5   stores, small market places and in inner-city

 6   communities.      I'm wondering if you have any

 7   comments about that kind of thing.

 8                  DR. PARKER: I know a lot of what I

 9   have    been   looking      at   for      communication

10   campaigns relates right now to H1N1 stuff.

11                  And this would be a very important

12   collaboration,       but    there    is     some    kind    of

13   umbrella organization for Salvation Army, Red

14   Cross, the shelter networks, the very large

15   ones, they do communicate, and I had already

16   written   that    down      as   one    of    the    absolute

17   needed partners, to go to these organizations.

18                  There are also a fair number of

19   faith     based        organizations           with        food

20   provisions, that particularly are very active

21   in urban areas, you know, and given what we've

22   learned   about,      you    know,     at    least,    for    a




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
                                                                      Page 187
 1   third, that's only a third.            I mean, that is a

 2   third, but it's only a third, if you correlate

 3   it with poverty, urban areas.

 4                 But    I    think    that's      a    wonderful

 5   network to tie into.        You can just go to the

 6   head of the Red Cross, tell them who you are

 7   and tell them you want to talk to them.

 8                 But the Red Cross, Salvation Army,

 9   there's a network, and then I'm not sure, but

10   I think there is another umbrella thing, that

11   relates to large distribution of food.

12                 So, I think both of those would be

13   very good partners and just talking to them

14   specifically about whether it's a poster, if

15   they've got a closed circuit TV with little

16   messages that are on it, you know, whatever.

17                 But    talking      to   folks       there,   to

18   find out, would be a great idea.

19                 CHAIR SEYMOUR: Dr. Reidenberg?

20                 DR. REIDENBERG: Yes, the business

21   is   that   sell    these   to     the   patients,       have

22   certainly    lots    of   information       on      their




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                            Page 188
 1   inventory and where it's sold, and it would

 2   seem to me that the place to go is where the

 3   people actually buy it, because they're the

 4   ones that need to get the message and the

 5   establishments that sell it, know what they're

 6   selling.

 7                 DR. HENDELES: Just to extend that,

 8   I think having a flag right on the counter,

 9   where the product is being sold now, that

10   says, "Talk to your pharmacist," and making

11   sure that the pharmacist is educated about

12   this, would probably be the most direct.

13                 But let me ask Marcus a question.

14    Do the homeless people in New York, can they

15   afford to buy a $23 inhaler?

16                 DR. REIDENBERG: I haven't a clue,

17   but what the study showed is that the children

18   aren't getting anything, and what the barriers

19   are, in addition to the money, is something

20   that needs looking at, because my concern is

21   that they have Medicaid, they have money, they

22   can't   get   to   the   pharmacy   that   has   the




                        Neal R. Gross & Co., Inc.
                               202-234-4433
                                                                    Page 189
 1   prescription, to enable them to pick up third

 2   party paid refill, and that's speculation.

 3                   I don't have any data, one way or

 4   another, as to how much this is a barrier for

 5   people      with    chronic     illness,    not   taking

 6   maintenance medicine.

 7                   CHAIR SEYMOUR: So, I think this is

 8   a --

 9                   DR.     LEONARD-SEGAL:        I'm     sorry,

10   Sally.

11                  CHAIR SEYMOUR: Dr. Segal?

12                  DR. LEONARD-SEGAL: Sorry, do you

13   know   if    Medicaid,     under      different     states,

14   covers over-the-counter medication?

15                  DR. HENDELES: They do not.

16                  DR. LEONARD-SEGAL: Okay.

17                  DR. HENDELES: There may be some

18   exceptions.        For example, in Florida, Medicaid

19   will   cover       loratadine    as    a   non-sedating

20   antihistamine, but as a general rule, Medicaid

21   will not pay for over-the-counter products.

22                  CHAIR SEYMOUR: Dr. Parker?




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
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 1                 DR.    PARKER:     I   think,     and   maybe

 2   this is just kind of a given and I didn't see

 3   it on the list and I was going to go back, but

 4   since you're there, let me ask you this.

 5                 It    seems   to    me     that   a   very

 6   important target and partner in this is going

 7   to be emergency room physicians and providers,

 8   because some of the users definitely have an

 9   episodic and acute care for exacerbation.

10                 So, I think, you know, when this

11   doesn't work, what do you do?           You probably

12   show up in an emergency room, saying, "I'm so

13   short of breath," you know, and so, I think

14   that it's really important to make sure there

15   is   clear,   concise     and    good    information

16   available in emergency rooms and that they're

17   very clear with the people who are coming in

18   there.

19                 If    you   have    been    using     this

20   product, it will not be available anymore.

21   Make sure you have a discussion and try to get

22   information on what you can do and where you




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                      Page 191
 1   need to go.     That's really important.

 2                  So,    I    would     say    the     provider

 3   community,     especially         emergency    rooms,      and

 4   health     departments,         where   a   lot of under-

 5   served populations present for primary care,

 6   that's another good target for the campaign

 7   and I had one other one, as well.

 8                  A great way to get health messages

 9   out to children and their families is through

10   schools.    So, school health nurses making them

11   aware, certainly, any of the kids who are

12   being seen and school nurses know they have

13   asthma, you know, a small card that goes home

14   with them to their parents, be aware, you

15   know, you need to be. That's where having the

16   message is clear, so that what we do is not

17   confused, but we really get them something

18   that makes it very clear to them that if

19   they've been using this, it's not there, after

20   a   certain   time,       and    it's    not   the    best

21   available treatment anyway.

22                 CHAIR       SEYMOUR:      I   think    all   of




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
                                                            Page 192
 1   these are great ideas and that's going to be

 2   what    we're    going   to   be   discussing   this

 3   afternoon, questions and answers about really,

 4   what the FDA can do and who to partner with.

 5                   We're a little behind schedule but

 6   we've built in enough time for lunch, just in

 7   case.    So, why don't we resume at 1:00 p.m.

 8   sharp, for the open public session.

 9                   We have a couple of speakers and

10   then following that, we'll have our roundtable

11   discussion with the questions and answers.

12   Thank you.

13                   (Whereupon,    the    above-entitled

14   matter went off the record at 12:02 p.m. and

15   resumed at 1:05 p.m.)

16                   CHAIR SEYMOUR: If everybody could

17   move towards taking their seats, we're going

18   to start the afternoon part of this meeting.

19                   So, we're going to begin our open

20   public session with a presentation by Nancy

21   Sanders, from the Allergy and Asthma Network,

22   Mothers of Asthmatics, and thank you, Nancy.




                        Neal R. Gross & Co., Inc.
                               202-234-4433
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 1               MS. SANDLER: Thank you very much

 2   for this opportunity to be here today.

 3               My name is Nancy Sandler.        I'm

 4   President and Founder of Allergy and Asthma

 5   Network/Mothers of Asthmatics.      We're a non-

 6   profit   organization,     based     in     Fairfax,

 7   Virginia, but we serve a nation of people with

 8   asthma, of all different walks of life.

 9               Our mission is to eliminate death

10   and suffering due to asthma, allergies and

11   related conditions and I think we're finally

12   at a time in our country's history, where that

13   can actually happen.

14               Our    organization    and    myself,   we

15   receive no compensation for being here today,

16   and not for any of our research or opinions or

17   results, and I think that we're suppose to

18   make that clear, right?

19               So, what we tried to do is answer

20   the five questions that were posted in the

21   Federal Register.    What is known about current

22   OTC/MDI usage?




                       Neal R. Gross & Co., Inc.
                              202-234-4433
                                                                          Page 194
 1                   Well, you know, the majority of

 2   people who contact our organization are not

 3   our members.        People who join our organization

 4   are    information      seekers       and    they       want   a

 5   strategic way of managing asthma at home.

 6                   But    the     majority      of     people     who

 7   contact      us,    through     our    patient         support

 8   center, do not have ready access to medication

 9   or access to care, and so, they are often

10   asking us to help them find it.

11                  So,     we    know     from    our      general

12   experience that there is a lot of people out

13   there who consider themselves poor and in need

14   of medication.        But none of them come looking

15   for OTC medications from us.

16                  So, we did an internet key word

17   research and the results came back, really,

18   that there's not a whole lot of people right

19   now,   who    are     asking    questions         or    having

20   concerns      about      any     type        of     transition

21   regarding Primatene Mist, specifically, that

22   is real current, at least not that we could




                           Neal R. Gross & Co., Inc.
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 1   find.    Most of it went back to 2007.

 2                   So, we decided, well, let's go to

 3   the Nebraska School of Nurses.            They have an

 4   inner-city      population.        They    have   rural

 5   population.        They    have    highly    Hispanic

 6   populations.      So, let's see what they say and

 7   our director of outreach services contacted

 8   them and they said, "You know, kids are not

 9   coming    to    school    with    these    medications."

10   There    were    only    three    exceptions that had

11   occurred and none of them were current, and

12   corrective measures have been following.

13                   Now, state laws, I want you to

14   take a look at this.        When we first started

15   the organization on this, no states had any

16   laws protecting the student's rights to carry

17   or use their prescribed life saving inhalers

18   while they were at school, and since that

19   time, we now have a law, working with a number

20   of groups and people in this organization,

21   that has incentivized states to create laws,

22   to protect students rights, to carry their




                        Neal R. Gross & Co., Inc.
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 1   prescribed medications, but it comes also with

 2   caveat, not only is it prescribed, but it also

 3   has to come with a written asthma action plan.

 4                There's only one state that needs

 5   to turn blue, and blue representing states in

 6   compliance with the 2004 Asthma Act and that's

 7   South Dakota, and we understand they're going

 8   to be turning blue in January, not because

 9   it's cold.

10                But so, you know, when you look at

11   schools across the nation, kids are not using

12   OTC bronchodilators at school.

13                From what we heard in Nebraska and

14   from the state maps and looking at the laws, I

15   just want to be careful about my statement.

16                When     you     look      at     OTC

17   bronchodilator MDIs, now, that Ventolin HFA is

18   available in the 60 dose, it's really not cost

19   effective for the poor and uninsured.

20                We also heard that earlier, but

21   one thing that I want to remind people of is,

22   current OTC bronchodilators do not have dose




                     Neal R. Gross & Co., Inc.
                            202-234-4433
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 1   counters on them and the medication actually

 2   runs out of inhalers before the canister is

 3   empty, and I'm sure Badrul can correct me or

 4   update    us   on     any    kinds       of    activities,

 5   regarding the guidance to industry, that was

 6   written five years ago, that said to industry,

 7   "Put     integrated         dose     counters        on     your

 8   inhalers, as you're developing the new HFA

 9   ones." And we wanted to applaud companies who

10   have done that, and those that we know are in

11   the process of doing that.

12                  So,    we    still     weren't       satisfied

13   that we knew who was using OTC bronchodilators

14   and we were concerned if we put out a survey

15   that   said,    you    know,       who    is    using     OTC

16   bronchodilators,       we    wouldn't         get   too    many

17   responses, because people might not know what

18   we were talking about.

19                  So, we put out the survey and did

20   it over Survey Monkey. Let me get my notes.

21                  Okay, this survey, when we put it

22   on Survey Monkey, we only left it up for 36




                          Neal R. Gross & Co., Inc.
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 1   hours, and that's because we had to prepare

 2   for this meeting.      So, in 36 hours, we got 124

 3   responses and you'll see that 92 percent have

 4   never used Primatene Mist or any other OTC

 5   bronchodilator.

 6                   Of the nine people who reported

 7   ever having used an OTC bronchodilator, none

 8   had used it within the last 12 months and of

 9   those eight said it will have no impact on

10   their lives, if and when OTC bronchodilator

11   MDIs are removed from the market.

12        98.4% of our respondents said that they

13   had health insurance and the majority have

14   prescription co-pays of more than $10.        Then,

15   you see that 41 percent of the total number

16   experienced life threatening episodes, but of

17   the nine former OTC bronchodilator users, 66.7

18   percent   had    had   previous   life   threatening

19   episodes in the past.

20                Now, you know, in answer to FDA's

21   second question, about, you know, sales data,

22   we're not a wealthy organization and we didn't




                        Neal R. Gross & Co., Inc.
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 1   raise the money to go get that data, but I

 2   think we're hearing from the manufacturer that

 3   there is not really a whole lot of data that

 4   tells us the difference between distribution,

 5   between     sales     and    between    actual    use   and

 6   refills.

 7                  So, we went to the next question,

 8   and so, well, what treatment alternatives are

 9   available for consumers who must switch?

10                  Well,    you    know     what?      We   help

11   families every single day who can't afford

12   their medications transition and certain many

13   of    the   organizations      that     Ruth    mentioned

14   before, but they're not helping them switch

15   OTC medications.       They're helping them get

16   their prescription medications.

17                  Many    of    these     programs    exist

18   around the country.

19                  So, these are two posters that we

20   have produced.      This one here helps patients

21   and   physicians      have    discussions       about   the

22   differences between CFC and HFA inhalers and




                         Neal R. Gross & Co., Inc.
                                202-234-4433
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 1   it answers a lot of their concerns and fears,

 2   and I want to thank the companies along the

 3   barn    here,    because       without      their help, we

 4   would never have been able to produce these

 5   two posters.

 6                   There's     also      another    alternative

 7   that people who purchase OTC medications may

 8   not be considering and that is the need for

 9   indoor air quality improvements, and so, we

10   developed, in English and in Spanish, a kit,

11   it's called "The Indoor Air Repair Kit", that

12   has low and no cost instructions for families,

13   so that they can make those changes in their

14   home,   room     by    room,    and    it's     been    very

15   successful.

16                   It's free and it's one of our most

17   downloaded PDFs on the internet.

18                   We really feel like part of the

19   question   here       is,   about     the    whole     OTC

20   discussion is, you know, is asthma a condition

21   that can be self-diagnosed and self-treated by

22   the average consumer, and I think we heard a




                           Neal R. Gross & Co., Inc.
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 1   few people here say this morning, no, and we

 2   heard some who were not quite so sure.

 3                 But 97.3 of those people surveyed

 4   on Survey Monkey, in fact, most of the people

 5   that we surveyed are not our members that I'm

 6   representing today.

 7                 But the majority said `no', and

 8   can we write our own asthma action plans?

 9   Absolutely not.      Asthma is not an OTC disease.

10                 When   we    look   at    your    question

11   about what are effective outreach strategies,

12   we've already talked about some of them.              This

13   is   a   different   transition     than    the    prior

14   transition.

15                 The transition for albuterol had a

16   lot of challenges, number one being the first

17   to    transition     and     number      two,     the

18   communications     program    for   getting      to    the

19   public was nothing like the communications

20   program our Federal Government, or excuse me,

21   Congress     mandated      for    the     television

22   transition, where each one of us can sight




                        Neal R. Gross & Co., Inc.
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 1   those ads that warned us that the television

 2   transition was coming.

 3                 But     we      also     had        with     that

 4   transition,    $80    vouchers       for   people        to

 5   purchase the little converter devices, if they

 6   needed them for their television and couldn't

 7   afford them.

 8                 There     was      no     such        program

 9   instituted    when    this     whole    transition         was

10   mandated 20 years ago.

11                 I'm not going to repeat all of

12   these things right here, except for the next

13   to the last bullet, because I think Ruth did a

14   great job with the messaging.

15                 But use appropriate terminology, a

16   lot of people like to call bronchodilators

17   rescue medications and consequently, a lot of

18   people don't even begin to think to use them

19   until they're almost dying.

20                 Then,     you     know,        in     health,

21   corticosteroids are not controllers.               We know

22   that many, many patients believe that their




                         Neal R. Gross & Co., Inc.
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 1   albuterol     or    their   Primatene    Mist   is    a

 2   controller because it controls their wheezing.

 3                    So, using appropriate terminology

 4   is very, very important.        Also, one thing not

 5   on this slide is telling patients what to

 6   expect, so when the new product does come out,

 7   letting them know what to expect before they

 8   even use it and make sure that they have the

 9   training.

10                 The lessons that we learned from

11   the   first   transition     about     education     and

12   outreach are enormous.       There are many of us

13   in this room that worked with FDA and EPA, to

14   make certain that the message got out and it

15   got to the right people, and while I think we

16   all   did   an     incredibly   good    job   and    I'm

17   thankful for the funding that we received when

18   ever we could get it, it wasn't enough because

19   it wasn't coming from the right people, and

20   the right people were the messengers, but we

21   weren't the ones who were changing the laws.

22                 And so, really, patients need to




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 1   hear from FDA and they need to hear it at

 2   point of purchase in a very clear way and they

 3   need to hear from the manufacturers as well.

 4                    This speaks for itself.

 5                    (Audio clip plays.)

 6                    MS. SANDLER: Talk about teachable

 7   moments.     You know, people with asthma, once

 8   we get a diagnosis, it's not like this, that

 9   we understand what we need to do, and in fact,

10   if you read any of the great books about how

11   the brain works and I'm fascinated by how the

12   brain works, you know that it is repetition

13   and demonstration and practice that creates

14   change, and we can, we can eliminate death and

15   suffering due to asthma in this country.

16                 It's    not   really   all    that    hard.

17   There   is   a    guide   book   called    "The    NAEPP

18   Guidelines" and we know that strategic care

19   does work.

20                 You      know,      having      an      OTC

21   bronchodilator is not the answer, no matter

22   what bronchodilator it is, but comprehensive




                         Neal R. Gross & Co., Inc.
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 1   care is, and I'm thankful for the opportunity

 2   to   speak   on    behalf     of   patients     who    are

 3   struggling to get that comprehensive care from

 4   even   our   Medicaid       programs    and    our    other

 5   public programs, because they're non-compliant

 6   with NAEPP guidelines.

 7                 So,     I      thank     you     for     this

 8   opportunity to share these perspectives and

 9   our organization will be here to help you

10   identify opportunities and I have to tell you,

11   non-profit   organizations         serve     people    that

12   don't have a lot of money.           So, we're always

13   looking for money, always, always, and without

14   it, we can't do the outreach programs.

15                So,     when    you're     thinking      about

16   partnering, and I know that that's part of the

17   plan, you know, just remember, we have less

18   money than you do.        Thank you very much.

19                CHAIR SEYMOUR: Thank you, Nancy.

20   Our next speaker at the open public session is

21   Charlotte Collins from the Asthma and Allergy

22   Foundation of America.




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 1                MS.      COLLINS:       Thank      you.    Good

 2   afternoon and thank you for inviting me to

 3   speak on behalf of the Asthma and Allergy

 4   Association,     which    is     a    national      not-for-

 5   profit foundation that offers free information

 6   to the public, offers educational programs to

 7   consumers    and       health        professionals         and

 8   advocates for support of public policies.

 9                I am the Director of Public Policy

10   and Advocacy for the Foundation and I'm not

11   like Nancy Sandler, I'm not being compensated

12   for being here today, except that hopefully,

13   my foundation will cover my paycheck in two

14   weeks.

15                So,    but    I'm       not   receiving      any

16   outside compensation.

17                I   want     to    thank      the    FDA    for

18   hosting this meeting, frankly. I think that

19   the approach to this transition is better than

20   the   approach   we    experienced         to    the    HFA

21   transition from 2007 and 2008, frankly, and I

22   think the idea of coming together, to look at




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 1   repercussions and to look at how to get this

 2   information out, rather than simply, how to

 3   get these products off the shelf, is really a

 4   step    forward      for    the     Food   and    Drug

 5   Administration and I applaud you on that, and

 6   I also applaud you because I've learned a good

 7   deal here this morning.

 8                 I'm going to focus my comments on

 9   frankly, the challenge ahead, and make some

10   specific recommendations for the agency, as

11   you move forward and as hopefully, we all move

12   forward together.

13                 As one of our scientific advisors

14   put it, Primatene is certainly inferior to

15   newer, more selective SABAs.        However, should

16   the public be left without an over-the-counter

17   SABA, necessitating that they see a licensed

18   care giver to obtain a prescription for a

19   rapid acting asthma reliever, or visit an ER

20   when ever they wheeze, perhaps it's a good

21   thing to require asthma patients to see a care

22   giver   for   long   term   care,    but   will   they




                       Neal R. Gross & Co., Inc.
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 1   comply?

 2                 So,    I   think    the    challenge   that

 3   we're really talking about, moving forward, is

 4   not the challenge that we faced before with

 5   moving    them   from    one    type    of   prescribed

 6   inhaler to another type of prescribed inhaler.

 7    But we're really talking about trying to get

 8   them into the kind of preferred care that

 9   we've known for a long time was out there, at

10   least ever since we had the asthma guidelines,

11   and how to do this.

12                 I mean, in a way, we're kind of

13   like a little trickle running into an ocean,

14   because for a long time, we've been trying to

15   get and we've been trying to put out messages

16   to get patients who suspect they have asthma,

17   who are going through asthma symptoms, into

18   care under the care of a licensed provider,

19   with   the   best    possible    medication     that's

20   appropriate for them.

21                 So, while I'm really happy to hear

22   that there may be an improved over-the-counter




                         Neal R. Gross & Co., Inc.
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 1   replacement product available before or at

 2   about      the    time    that     the current Primatene

 3   product is withdrawn, I think we shouldn't

 4   lose this opportunity to try to get these

 5   patients into a system of care.

 6                     It's tough, you know, and we've

 7   all been trying to do it from a number of

 8   different        standpoints,       and    I'm   happy    that

 9   again, we have the engagement of the Food and

10   Drug Administration on this one.

11                    This     is,    indeed,     a   teachable

12   moment, and our patients are most teachable at

13   the point that they're most vulnerable and we

14   talked about the point of sale, but the point

15   of sale is kind of a tricky place too, because

16   one   is    coming       in   in    distress,     especially

17   distress from not being able to breath, you're

18   thinking about a couple of things.

19                    I   mean     you're      thinking   about

20   dying, you're thinking about, how can I get

21   relief, and that's immediate.

22                    So,     being     confronted     with,   you




                            Neal R. Gross & Co., Inc.
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 1   know, posters and that kind of media, you

 2   know, you're going to miss a little bit in the

 3   translation.

 4                    So, I think we should work with

 5   that, but maybe that message is best delivered

 6   by    a   health     professional.           Maybe    this    is

 7   really     a   good    reason     for      putting    certain

 8   products behind the counter, so that patients

 9   have to go through some level of a health

10   professional, even if it's a pharmacist, in

11   order to get that and maybe they can get some

12   better    direction.          Maybe     they   can     get    a

13   stronger message from an individual than they

14   would from a card hanging off of a shelf.

15                  The        challenges           here          are

16   unprecedented.        We make a lot of assumptions

17   about      the        users      of        over-the-counter

18   epinephrine      products      and    I    think     we've

19   established here today, that you know, while

20   we don't know a lot and there's a lot of room

21   for   additional       research      and    maybe     this

22   research can be conducted along with some of




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 1   the    funding     and    the     push available around

 2   comparative effectiveness research.                      You know,

 3   that's just a possibility that I would throw

 4   out.

 5                    I do know that there is a lot of

 6   funding       becoming    available          for       comparative

 7   effectiveness research.

 8                    So,    the     major    issue          is   how    to

 9   transition people from a product and self-

10   care, to provider directed care, and again,

11   that's really challenging.

12                   I'm     going     to    make       a    couple      of

13   recommendations,         in   a    couple      of       different

14   categories.

15                   The first is directed at what can

16   FDA do?      What can the agency do directly, and

17   my    first    recommendation          had    to       do    with

18   labeling and putting a prominent notice on

19   these products, while they remain available

20   and    I'm    really     happy     to    hear       that      that's

21   already being done.

22                   My second recommendation is, you




                            Neal R. Gross & Co., Inc.
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 1   know,    again,      to    require       pharmacists to at

 2   least be consistent in how they handle these

 3   medications and preferably, to put them behind

 4   the counter.

 5                  Now, I heard earlier that you've

 6   concluded or maybe concluded, that you can't

 7   do this without an act of Congress. You know,

 8   I don't know.        I don't have an answer to that.

 9    If   you've    already       investigated        that,   and

10   that's the case, and you need partners to go

11   to Congress with you, sign me up, because I

12   think it's really important to have that third

13   way of accessing medications, you know, beyond

14   just prescription and over-the-counter.

15                  And    the    third       recommendation    or

16   request I would have is, to offer a listing.

17   There are a number of these medications that

18   are   being    slated      for   withdrawal over, you

19   know, CFC based medications that are slated

20   for withdrawal over the next few years.

21                  It    would    be     really    helpful    and

22   handy,   to    me,    to    have     a    list.   An   easily




                          Neal R. Gross & Co., Inc.
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 1   acceptable    table       of   these   medications,       by

 2   brand name, if possible, so that our providers

 3   can get really specific direction about what's

 4   available, when and when it's going to be

 5   withdrawn.

 6                 I don't know whether you have that

 7   in the works or even have it somewhere, but

 8   that would be really helpful and you could do

 9   that directly.

10                 So, that's direct action.           But I'm

11   going to suggest that FDA can be much more

12   effective in collaboration with others, and

13   I've had some really happy meetings lately,

14   with other Government agencies.

15                 One of the things that I've been

16   trying   to   do    is    to   connect    with    all   the

17   different departments, offices and so forth,

18   in different agencies and bureaus, who are

19   concerned with asthma and allergies, to talk

20   about collaboration on a number of fronts.

21                 One    of    the   things    that    I've

22   learned is that the centers for Medicare and




                         Neal R. Gross & Co., Inc.
                                202-234-4433
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 1   Medicaid services, or CMS, is gearing up for a

 2   big outreach campaign to enroll children in

 3   the state children's health insurance program,

 4   also known as CHIP, and you know, why not try

 5   to link with some of their activities, about

 6   the   availability      of    CHIP   for     low   income

 7   children, some messages related to asthma,

 8   because, you know, we've already established,

 9   there is just an outsized burden of asthma on

10   children and especially poor children.

11                Why not include those messages in

12   the   materials    in   the    media,      that    they're

13   putting out, related to that, that you know,

14   Primatene is being withdrawn, for instance.

15                Social security administration is

16   also involved in doing outreach on a regular

17   basis, every year, around the prescription

18   drug plan under Medicare Part D, and that

19   targets the elderly, but it's also a good way

20   to target care givers who may be care givers

21   for elderly parents, but are also care givers

22   for   children    who   may    have,    an    outsized




                       Neal R. Gross & Co., Inc.
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 1   prevalence of asthma.

 2                   Finally, I will mention the CDC

 3   and the EPA, who we work with pretty directly

 4   on    asthma    programs,      but    they    also    have

 5   networks of community groups, all across the

 6   country, on both regional and local levels,

 7   who are doing their own outreach.

 8                   And I'm going to also mention our

 9   association,      AAFA,      which    works    with    local

10   chapters, but we also work with almost 100

11   educational      support     groups    all    around    the

12   country, that provide relevant information to

13   people   who     are    in   support    of    each    other,

14   related to their severe asthma and allergies,

15   and   they     offer    both   emotional support and

16   educational support.

17                   And I'm suggesting that FDA could

18   collaborate      with    those   groups,      as well as

19   provide groups like us with, when you develop

20   these, you know, tools on your website, send

21   us some widgets.        We'll put them up on our

22   website and we'll try to disseminate them and




                        Neal R. Gross & Co., Inc.
                               202-234-4433
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 1   it may not be as viral as the House video,

 2   which I'm glad you showed, but to the extent

 3   that   you   have    video,    we    can    help    to

 4   disseminate    that    across      the,    you   know,

 5   blogosphere and the worldwide web.

 6                 I'm     also     going       to    mention

 7   community    health    centers.        I    don't    know

 8   whether you've reached out to community health

 9   centers yet, but community health centers,

10   when people have nowhere else to go, if their

11   community health centers in their communities,

12   they offer health care on a sliding fee scale,

13   and that may be a good place to try to get

14   traction with low income communities, related

15   to this particular message.

16                 It's    also    an    important      way   to

17   reach those providers. Again, these providers

18   are dealing with a whole lot of issues, not

19   just asthma, and not just severe issues.

20                 So, why not get those messages to

21   them and try to focus some specific training

22   on those providers, and one of the things that




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                Page 217
 1   we found out when we surveyed late in the

 2   summer, about the HFA transition, one of the

 3   things that we found out, we asked a question,

 4   you know, where did you get your training on

 5   how to use your new inhaler?

 6                  Thirty-three percent of them said

 7   that they didn't get the training from their

 8   physicians.       A lot of them didn't get the

 9   training anywhere.

10                 So,    that's    something   that    we

11   really need to look at, because again, a lot

12   of people who are having their asthma managed

13   by   a   professional    provider    are   not    using

14   specialists.      They're using generalists.

15                 So,     beyond     community    health

16   centers and the communities and action groups

17   around the country, and pharmacists,         the FDA

18   is in a prime position to help tenderize the

19   providers about providing adequate training

20   for their patients.

21                 I     think     the   pharmacists      are

22   another key provider group that we may be




                         Neal R. Gross & Co., Inc.
                                202-234-4433
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 1   under-estimating their ability to get these

 2   messages out.

 3                  So, let's try to work with the

 4   pharmacists.          What    we   did    during      the   HFA

 5   transition     is,     we    worked     with    one    of   the

 6   pharmacy associations, to try to get these

 7   messages   into       their    news     letters and onto

 8   their websites.

 9                  So, a lot of them actually had a

10   good deal of knowledge about it.

11                  Some    public      health      programs     are

12   working creatively to offer screenings and

13   education programs in barber shops and beauty

14   salons   and    other       non-traditional       centers,

15   where people go, not necessarily for health

16   seeking behavior, but where they at least go

17   on a regular basis.

18                  Examples        included        the    Harlem

19   Children's Health Zone Asthma Initiative and

20   the   University      of     Pittsburgh's       Lay-Health

21   Advocates Training Program.

22                  So,    looking      at    non-traditional




                          Neal R. Gross & Co., Inc.
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 1   places for people who are already linking to

 2   low income people is probably a good idea and

 3   if     you    provide       flyers      and online content,

 4   again,       we    can     get    the    information      out   as

 5   associations,             but     there     are      also     the

 6   professional           associations       that     meet   every

 7   year,        like        the     American        Public     Health

 8   Association and the American Association of

 9   Pediatricians, and they can provide a forum

10   for the professionals and meeting attendees.

11                      And         I'll      close     with     this

12   recommendation.                Well,    there    is one other

13   point I want to raise.

14                      Yesterday, I was at CMS and we

15   were talking about trying to mutually support

16   each    other       and    disseminating         interesting

17   messages and one suggestion that I heard, but

18   I hadn't really thought of, is the libraries.

19                      Well, one great thing about the

20   libraries         is   that      it's    unlike the schools

21   system. You know, you go to a school system

22   with a program, they really don't want to hear




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 1   from you because they are up to here with all

 2   these requests to get things in the curriculum

 3   and they're really trying to teach to the

 4   standardized tests now.          So, they don't have

 5   room for anything new.

 6                    The libraries, I understand, are

 7   exactly       the   opposite.        They're    actually

 8   looking for content programming and they're

 9   also a site, they're almost kind of a safety

10   zone within the communities where they sit for

11   kids    who    go    there   after    school,    for    the

12   elderly    who      come   in   on   the   weekend     for

13   program.      Sometimes, they're co-located with

14   senior centers and health centers.

15                   So, think about the libraries, as

16   you're reaching out to try to find sites to

17   put these programs, and I'm going to close

18   with this recommendation, really close this

19   time.

20                   The FDA should identify funding to

21   create a community outreach campaign and fund

22   partners, who can reach communities that we




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 1   think will be impacted.

 2                   You     know,    if    you    can     find       the

 3   funding, fantastic. If you can't, you know,

 4   allocate      the    funding     from    your     immediate

 5   budget, I understand.

 6                   But maybe working in partnership,

 7   we can go to not-for-profit foundations who

 8   are in a position to fund campaigns of this

 9   size    and    with     this    magnitude       and    let's

10   describe      the   campaign     as     not    trying       to

11   transition from one OTC to another OTC.                    Let's

12   describe the campaign as trying to get people

13   into    a   system     of   affordable        care     that's

14   accessible to them, and that's actually going

15   to be the best effective medicine for their

16   asthma.     Thank you.

17                   CHAIR    SEYMOUR:       Thank    you       .   I

18   believe those were the only individuals signed

19   up for the open public session.               Are there any

20   other    statements      from    any     groups       in    the

21   audience?

22                   Okay, yes, if you want to come up




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 1   to the podium and introduce yourself.

 2                  MS.    HARWICK:       Hi,    my    name    is

 3   Maureen Hardwick and actually, I didn't plan

 4   to speak.     I don't have any formal comments,

 5   but I just was inspired to say briefly that

 6   I'm here on behalf of IPAC, which is the

 7   International              Pharmaceutical            Aerosol

 8   Consortium, which was formed in the late 1980s

 9   in response to the Montreal Protocol.

10                 It's a group of meter dose inhaler

11   companies    that     manufacture      medicines         for

12   respiratory    illnesses,       that       came    together

13   under this unique situation and IPAC's mission

14   for many years now, has been to promote a safe

15   and timely and effective transition to HFC,

16   MDIs, and others, CFC-free alternatives, while

17   at the same time, being very cognizant of

18   patient   health      and    making    sure       that    the

19   transition    was     as    smooth    for     patients      as

20   possible.

21                 So, I just wanted to thank FDA for

22   organizing what I think has been an excellent




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 1   meeting and echo Charlotte's comments, really

 2   good thinking, really great speakers, and I

 3   know    personally,      while     IPAC    didn't have a

 4   formal position in response to the Federal

 5   Register    notice,      our    companies       include    at

 6   least     three     of       the    major       albuterol

 7   manufacturers, GSK, Teva and Sepercor, which

 8   makes levalbuterol.

 9                 So,    I    will     be    at    a   board   of

10   directors meeting of IPAC's next week.               I will

11   take back all of the interesting comments of

12   this meeting and encourage our companies all

13   to think of ways that we can be helpful and

14   partner in this efforts, so, thank you.

15                CHAIR SEYMOUR: Thank you.              Anyone

16   else?   Okay, just introduce yourself when you

17   come up to the microphone.

18                MR.     ESTRELLA:      My     name    is   Mike

19   Estrella and I work for Boehringer Ingelheim.

20    We make one of the CFC inhalers.

21                First,      I     wanted     to   thank    Dr.

22   Parker for a very inspired presentation.




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 1                 I have a suggestion perhaps, for

 2   to find out where these folk are.         I know we

 3   found some very important information from our

 4   patients, and they really are the experts.

 5                 So, you guys know where your folks

 6   who complain live.        You get complaints.    We're

 7   Americans.    We complain.      If it's not perfect,

 8   we're going to let you know, okay.

 9                 So,    you    could   probably   fairly

10   easily    gather    the    cities   and states where

11   these folks live and it may be helpful.          Look

12   at the last five years or so, okay, that's all

13   I wanted to add.      Thank you.

14                 CHAIR SEYMOUR: Thank you.        Anyone

15   else?    Okay, I think then we'll begin the

16   discussion part of the afternoon and I hope

17   everyone was able to pick up a copy of the

18   questions that we plan to move through.          If

19   not, I believe there are some out front.

20                 MS. DUGAN: The questions will be

21   up on the screen.

22                 CHAIR SEYMOUR: Well, you may not




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 1   have gotten a copy, but we're going to post

 2   them, and what we're going to do is, we're

 3   going to walk through these questions and I'm

 4   going to pose the questions to the committee

 5   and just have a discussion.

 6                   There is quite a few questions to

 7   get through, but there is a lot of overlap.

 8   So,    I    think    I    look     forward    to    a   good

 9   discussion, and some of these, we've already

10   touched on in the morning session, and I think

11   the first place that we wanted to start was,

12   what are the goals of an educational campaign

13   on    the   phase-out       of   the    OTC/CFC-propelled

14   epinephrine inhalers?

15                  And       so,   I'll    pose   this      to    the

16   roundtable for discussion.

17                  DR.       REIDENBERG:     I'll      break     the

18   ice.   I think that the goals are for people to

19   know that this will no longer be available,

20   what the alternatives are and that if they

21   have   bad    asthma,       they    need proper medical

22   care, quickly.




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 1                 CHAIR SEYMOUR: Anyone else?           Are

 2   those kind of some of the messages that we

 3   were    overlapped    a   little   bit,    with     the

 4   messages that Ruth brought up, or are the

 5   messages and the goals the same?

 6                 DR. PARKER: I think the campaign

 7   itself has got more than one component.

 8                 I think the goals of the campaign

 9   are to identify the essential messages and I

10   would limit that to three to five, something

11   that you can actually get your hands around,

12   in terms of content, understand what they are,

13   from sort of the evidence, the best available

14   evidence and fact.

15                 You know, the factual information,

16   the evidence and they also need to be grounded

17   in     evidence-based     clinical       practice     of

18   medicine.      They   need   to    be,    you   know,

19   concordant with the best care possible, from

20   clinical medicine and they need to be clearly

21   communicated and actionable.

22                 The campaign itself, I think the




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 1   effectiveness       of    the    campaign    is how well

 2   this,    you   know,      clearly      communicated    and

 3   understood content actually reaches those who

 4   need the information most and it's definitely

 5   the users, but it's also those who come in

 6   contact with the users.

 7                  So,    I    think    as    part   of   the

 8   campaign, touching these other points that

 9   have been coming up through the discussion are

10   also part of designing the campaign, making

11   sure    that   we    clearly     identify where these

12   other people, the users themselves, but also,

13   those that come in contact with them on a

14   regular basis, be it where they live, where

15   they shop to buy the products, where they get

16   care    emergently,       when   the     use of whatever

17   isn't working and they present for acute care,

18   but making sure that we very clearly identify

19   those, are all parts of it.

20                  DR. CHOWDHURY: If I could make a

21   comment, for others to make a comment on my

22   comment.




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 1                   I   think    what    we    heard,    as   the

 2   message    in    the   morning      presentation      and

 3   subsequently is for patients who are using

 4   epinephrine         over-the-counter            inhalation

 5   product to use alternate product, which are

 6   prescription product, going to physicians.

 7                   That essentially means albuterol,

 8   for the most part, and I think part of the

 9   goal of the campaign is really not to tell us,

10   the FDA, what to do, but what we all can do

11   and the point I want to raise up here is, what

12   do   you   think    the     role    of    the   albuterol

13   manufacturers here could be or should be or

14   can be?

15                   As we heard, IPAC-RS say something

16   to that effect, because she was presenting the

17   part on the albuterol manufacturer here.

18                   So, what do you think their role

19   should be here or is there a role for them at

20   all here or not?

21                   CHAIR SEYMOUR: Dr. Hendeles?

22                   DR. HENDELES: Just to answer Dr.




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 1   Chowdhury's specific question.         One of the

 2   things that I think they are doing, that I

 3   think is important, is they're providing free

 4   samples   of     their    albuterol   inhalers     to

 5   physicians and for somebody who especially is

 6   poor and can't afford the nonprescription or

 7   doesn't have access, if they do get to a

 8   physician or even to a health department, they

 9   would have access to that, because there are

10   sufficient free supplies available, from all

11   four of the manufacturers are now sampling.

12                  DR. CHOWDHURY: Anything else that

13   I think one can think about for them doing,

14   because   part    of     the   transition   will   be

15   impacting them in some way.         The product will

16   be increased more.        There are more persons

17   directed with that.        Anything else that you

18   can think about, or one can think about.

19                  DR. HENDELES: Well, certainly, if

20   you can get this down to a bit-size message,

21   they're very good at handing out information.

22   They've summarized the NAEPP guidelines, as




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 1   to severity and step care and things like

 2   that,    and    distributed        it   to     health   care

 3   professionals.        So, that would be a way that

 4   they could help us out.

 5                   CHAIR SEYMOUR: Dr. Parker?

 6                   DR. PARKER: I think it's a golden

 7   opportunity too, to really challenge them to

 8   collaborate on patient centered education and

 9   messages      about    the    use    of    bronchodilating

10   medicines, and I say this for two reasons.

11                   I   think    you    could      build    the

12   business case, that they'll benefit by it.

13   It's the right thing to do.             Let me get very

14   specific.

15   These medications are very expensive and when

16   you don't use them correctly, you probably

17   also    use    or   "waste"    more       of   the   content,

18   meaning that you have to go buy more, well you

19   could say, well, that's good for people but

20   nobody really wants that.           That's not good

21   business for even the manufacturer.

22                   So, I think, you know, be very




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 1   clear     to    everyone       that,      from       a    patient

 2   centered standpoint, and I would argue that

 3   patient centered is that pillar of quality.

 4   You know, many of us can list what they are,

 5   IOM, blah, blah.            It's great, but patient

 6   centered is the one that's been the hardest to

 7   do.    It still remains somewhat of a black box,

 8   really making things patient centered, making

 9   it more about the patient than it is about a

10   lot of other things.

11                    But    I    think     from      a       patient

12   centered       standpoint,      this      is     a       wonderful

13   opportunity to ask the manufacturers to really

14   work    together,       to    try    to    help          people

15   understand and remember how to correctly use

16   inhalers, because in doing that, I mean, it's

17   wonderful that there are clinics, there are

18   specialty clinics where this is standard of

19   care in the clinic.

20                    There is regular review.                  There is

21   regular    demonstration.              There      is       regular

22   teach-back.       It all happens, but that is not




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 1   what's happening with most of the prescribing

 2   and dispensing of inhalers.

 3                   Products are expensive.              Time is

 4   limited, when you pick them up and it's hard

 5   to    remember,     particularly          if    you're     an

 6   episodic      user,    and    you    don't       use    them

 7   regularly, you have to remember, you have to

 8   retrain and one of the very confusing things

 9   that patients experience is, it's hard when

10   everybody is telling you how to do it just a

11   little differently and trying to tell you that

12   that matters, and you're just the individual

13   trying to get through the day and take your

14   inhaler, so you can breathe better.

15                  And so, we actually need to come

16   together on this and we don't need to teach

17   people   five     different        ways    to     use    their

18   inhaler correctly.          We need to come together

19   and   agree    on     it,    and    then       let   all   the

20   manufacturers try to put this out there.

21   It's a wonderful opportunity to try to advance

22   patient education, but doing it right, so that




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 1   it's not confusing, that it's clarifying.

 2                Let    me    just   give      you    another

 3   example.   There's nothing intuitively obvious

 4   about a stop light: red, yellow, green.                If

 5   you didn't know what they mean, and you just

 6   saw them, you wouldn't know what it meant.

 7   But they all look alike, and they have the

 8   same meaning and they control traffic, because

 9   we   approach      them     with        this     common

10   understanding of what they mean.

11                If each of your inhalers has an

12   insert and has instructions that are different

13   and you try to put all those together,             it's

14   really confusing.

15                So, I would say coming together

16   and encouraging the manufacturers to take this

17   opportunity to do something for people who

18   have bronchospastic disease and restrictive

19   airway   disease    and   want     to    know    how    to

20   actually use those inhalers, it's a wonderful

21   opportunity to advance that and it's a model

22   for chronic disease, which is a driver of




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 1   health care cost in our country.

 2                  So, it's sort of challenging the

 3   manufacturers to use this opportunity, knowing

 4   that there is going to be an uptake in use,

 5   potentially     of their products anyway, but use

 6   this opportunity to do it right.

 7                  CHAIR SEYMOUR: Dr. Liu, I think

 8   you had a comment.

 9                  DR. LIU: I guess I'm kind of just

10   reiterating what has been said, but in my own

11   way of looking at this, this is, you know, a

12   fairly straight forward issue.

13   I mean, the decision has already been made.

14   So,   there    are    basically   only two messages

15   here.

16                  One is that it's happening and the

17   date it's going to happen and then the second

18   is, that if they're using this as a regular

19   asthma medication, they should be under the

20   care of a physician, period. Because I just

21   think   that    for    the   evaluation   and   the

22   management of anybody that has, you know, more




                          Neal R. Gross & Co., Inc.
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 1   than an intermittent problem, there could be

 2   some very general thing, if you use this on a

 3   regular basis, you should see a physician.

 4                   Those are the kind of people that

 5   need to be identified and should be under the

 6   care of a physician, and then beyond that, you

 7   know, I don't know how you want to embellish

 8   it or where you go with this, but        I think

 9   we're really sort of, at a loss, to some

10   extent, because we don't know who and how

11   people are really using this medication.

12                But    if   they   really   are   the

13   intermittent user, what they're doing may be

14   quite appropriate, but if it's not, and there

15   are some people out there, and I know that

16   I've seen these people, that really are using

17   it daily or you know, I mean, excessively,

18   then they need to see somebody because they're

19   not   getting    the   appropriate   care of their

20   asthma, which might wind them up in a much

21   more severe condition, winds up spending a lot

22   more money, because they get admitted to the




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 1   hospital or they're not managed properly, or

 2   they don't have asthma and they're treating

 3   some   other    condition     that   really     doesn't

 4   respond to this medication.

 5                  CHAIR   SEYMOUR:       I    think     Dr.

 6   Reidenberg was first.

 7                  DR. REIDENBERG: Yes, I'd like to

 8   support Ruth's idea.       If we're asking, what is

 9   the manufacturers' responsibility, then it's

10   clearly to have the customer use the product

11   properly, and I think this is really primarily

12   the manufacturers' responsibility, for this or

13   any other product, and where for the inhalers,

14   there is a specific technique that has to be

15   used for it to work.

16   Then   the   one   thing    that,    to   me,   is

17   unequivocally           the            manufacturers'

18   responsibility is to help the patient buying

19   it use it correctly.

20                  I think that we who prescribe it,

21   have the responsibility.       I think the people

22   who dispense it have the responsibility, but




                        Neal R. Gross & Co., Inc.
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 1   there's no question, manufacturers have the

 2   responsibility for enabling the customers to

 3   know how to use their products properly.

 4                   CHAIR SEYMOUR: Dr. Hendeles?

 5                   DR.    HENDELES:     I    just      want    to

 6   expand on what Dr. Liu said, and I think I

 7   heard     him   say    that    if   they      were    having

 8   persistent asthma, but I think anybody who has

 9   been using Primatene Mist, needs to see a

10   doctor,    because      it's    going    to    go     off    the

11   market and that way, the doctor can confirm

12   the   diagnosis,       I   should   say    health         care

13   provider, it could be a nurse practitioner.

14                   But    the    diagnosis    has       to    be

15   confirmed and the patient has to be assessed,

16   in terms of whether they really are mild and

17   intermittent.

18   So, I think the bottom line message is, it's

19   going off the market and you need to see a

20   doctor.

21                   DR. LIU: It's very simple. I could

22   easily agree with that.




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 1                     CHAIR SEYMOUR: So, I think we kind

 2   of skipped down a little bit, to messages.

 3   So, I think we've covered the goals, broad

 4   enough.

 5   But let's go back and see if we can get some

 6   more information about the audience and then

 7   we    can    talk    a    little      bit     more    about     the

 8   messages,      which      I     think    is    some    of     the

 9   discussion that we were just having.

10                  But I think it's important to try

11   and   sort    out,       what    do     we    know    about    the

12   consumers of the epinephrine MDIs?                   There is a

13   lot of different types of information we are

14   looking     for,     demographics,           what    motivates

15   them, where they purchase the information, and

16   so, I'd like to have a little discussion on

17   that.

18                  DR. HENDELES: Excuse me, can we

19   invite Diana Schmidt to the table?

20                  CHAIR SEYMOUR: Absolutely.                Come

21   on    up,   Dr.     Schmidt.          Yes,     go    ahead    and

22   introduce yourself, I'm sorry, we started the




                          Neal R. Gross & Co., Inc.
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 1   discussion without you, but please.

 2                    DR.     SCHMIDT:      Yes,      I'm     Diana

 3   Schmidt.     I coordinate the National Asthma

 4   Education and Prevention Program out of the

 5   NHLBI, and I find this a very informative and

 6   fascinating discussion and glad to be a part

 7   of it.

 8                    CHAIR SEYMOUR: Thanks for joining

 9   us, and perhaps, I know you presented some

10   information about the consumers. Is there any

11   other way you can obtain information about the

12   consumers, any further information that you

13   can provide to us, about the users of the

14   product?

15                 MR.        CAMPBELL:      I     think    the

16   suggestion       made      by    the     gentleman       from

17   Boehringer is an appropriate one and I do have

18   a number of years of complaint adverse event

19   data, that I can go back and review and at

20   least get some inkling          of the demographic,

21   and   I   will    do     that   and    provide    that

22   information to the agency.




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 1                    CHAIR SEYMOUR: Dr. Parker?

 2                    DR. PARKER: So, help me here, but

 3   it     sounds      like      there      is   proprietary

 4   purchasable       data     available,     about     who    is

 5   selling what volume of this product and is

 6   that     correct?     Is    it   known, does somebody,

 7   somewhere know where these four million per

 8   year come from? Let me make sure I understand.

 9   Is it this or is it this, plus the refills,

10   equals    four    million?        I'm    just     trying    to

11   understand.

12                   MR. CAMPBELL: It's that plus the

13   refills.

14                   DR. PARKER: Okay, so, this plus

15   the refills that are sold separately.               Okay,

16   so, there's a total of about four million of

17   these being purchased in the United States.

18                   Is it possible to find out where

19   those are being purchased?           Is it possible?

20                   MR.    CAMPBELL:     That    data    is    not

21   purchasable at this point in time.              It is held

22   very tightly by the chain drug stores.               It's




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 1   their data and they've chosen not to release

 2   it.   It's not available through IMS.

 3                 DR. PARKER: So, I guess I don't

 4   understand why.      That would be a different

 5   question, but that would be important, and let

 6   the record state, it would be very helpful,

 7   from a public health standpoint, to be able to

 8   access data that exists, but we cannot obtain,

 9   about where these are being used, in order to

10   adequately    inform   a    population    about    this

11   issue.

12                 DR. CHOWDHURY: Just a comment on

13   that. I mean, this is a very important point

14   and   I'm   pretty   glad    that   you   made    the

15   statement, it should stay in the record, and

16   we actually had very similar discussions when

17   we had the initial public advisory committee

18   meeting, before we put out the proposed rule

19   for removal of the product, trying to get the

20   exact same information, and it was the same,

21   or similar stumbling block.

22                 So, if anybody can help us with




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 1   that, anybody has information or can guide us,

 2   we would appreciate to hear that.      Thank you.

 3               CHAIR SEYMOUR: Is there anyone in

 4   the audience from a chain drug store, that

 5   represents chain drug stores, that might be

 6   able to comment on whether this data can be

 7   obtained?

 8               DR.    PARKER:   So,   maybe   just   a

 9   follow up to this would be an official contact

10   with the association of chain drug stores,

11   for, in writing clarification of the specifics

12   about trying to access data about volume and

13   sites of purchase for a product that's coming

14   off the market, in order to be able to inform

15   purchasers, about the removal from market with

16   advice on safe precautions and health advice

17   related to the product withdrawal, something,

18   you know what I'm talking about.     Just work on

19   that.

20               CHAIR SEYMOUR: Any other comments

21   about the audience, because I think we covered

22   both questions under the audience, which was




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 1   what we do know and how we can find out more

 2   information.

 3   Any other ideas?         Anyone in the audience have

 4   any suggestions?         Sorry, Dr. Reidenberg?

 5                 DR. REIDENBERG: Yes, where we're

 6   talking   about     an     audience     and   we've    been

 7   talking about a different message of getting

 8   medical care, then the homeless children in

 9   New   York   and    inner-urban        patients and the

10   inner-city study, all have repeated contact

11   with physicians in emergency departments.

12                This     is    where     they    get    their

13   medical   care     and    we   ought    to    think    about

14   having the audience of emergency department

15   physicians, recognizing that this is where

16   these urban individuals get their medical care

17   and   therefore,     if    we're    going     to    change

18   anything, these are the doctors that are going

19   to have to change it, not simply refer them to

20   the hospital asthma clinic. It doesn't work.

21                CHAIR SEYMOUR: Thank you.              Anyone

22   else about the audience?         Dr. Schmidt?




                        Neal R. Gross & Co., Inc.
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 1                  MS. FITZPATRICK : Is it possible

 2   to get like, maybe not super-specific, for

 3   which chain drug stores are going to but would

 4   distributors,     provide    any,     do   you    think,

 5   information     about    even     concentrations       of

 6   states   or    rural    areas   or    urban   areas    or

 7   anything like that?

 8                  MR. CAMPBELL: At this point, we're

 9   distributing directly to the chain drug store

10   distribution     centers.            So,   it's     their

11   proprietary units that it goes into, and we

12   lose all traceability of the material after

13   that, unless there were a product recall or

14   something,    then they have to provide it to

15   us, but I don't want to go out and recall the

16   product, just to get data.

17                 CHAIR SEYMOUR: Dr. Schmidt?

18                 DR. SCHMIDT: I'm not sure if this

19   fits into the scheme of how this all works,

20   but it seems that there's a lot of emphasis on

21   trying to figure out where the audience is.

22   The best we know is probably in low socio-




                       Neal R. Gross & Co., Inc.
                              202-234-4433
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 1   economic areas and we have sort of a surrogate

 2   way of finding where those areas are.

 3                     When I saw the actual product, I

 4   think it was Dr. Parker who had shown us the

 5   box, with the label on it.            The people who are

 6   buying it, you know, how can you get anymore

 7   direct      than    that?      They     kind   of   find

 8   themselves.

 9                     I don't know, the label on the

10   box, I thought, was very good, because it said

11   if you have asthma, then you need to be seeing

12   your doctor, and it sounds like you're putting

13   the label on the outside, as far as announcing

14   the December date as the end of when this

15   would be available.

16                  I don't know if there's a way to

17   set up a hotline or something, where people

18   who purchase this, can call a number and find

19   out what's going on.          It would be nice if on

20   the   box    or    in   the    store,    wherever    the

21   Primatene Mist, maybe to state when you see

22   the pharmacist or the cashiers are clued into




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
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 1   knowing that these are folks that need to

 2   understand that they could be in trouble and

 3   they need to get some information.

 4                   So, the pharmacies can have the

 5   cashiers,      sort    of   knowing     about    this     and

 6   giving some information or handing something

 7   out, the pharmacists knowing this.

 8   But    maybe    the    person     who   is   buying      it

 9   themselves, you know, would be curious what's

10   going on here?        Why is it going off market,

11   and have a place to call.

12                  DR.      LEONARD-SEGAL:       So,      you're

13   advocating putting a hotline telephone number

14   on the package itself, on the drug facts, at

15   the bottom of the drug facts label or off the

16   bottom of the drug facts label, under `other

17   information', that kind of thing?

18                  DR. SCHMIDT: That's my thought.                I

19   mean, it seems like we're having such a hard

20   time   figuring       out   who   the   people     are    and

21   granted, not all of them are going to call,

22   but they're going to be curious, what's going




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
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 1   on, because there isn't enough space on the

 2   label to explain, you know, this is a CFC

 3   issue     and   environmental       and    so    on     and   so

 4   forth.

 5                   They might think there's something

 6   wrong with the product, it's going to poison

 7   you, why are they taking it off, you know, how

 8   do you get those questions answered?

 9                   DR. LEONARD-SEGAL: Well, actually,

10   I think you raise a very interesting question,

11   so, I'd like to ask Steve.           I'd like to ask

12   you. Sorry, on the bottom of the label, you

13   have a telephone number for contact.

14                   MR. CAMPBELL: Yes, we do.

15                   DR.    LEONARD-SEGAL:       Because      it's

16   usually    there.        Is   it    possible      for    that

17   contact, at that contact number, to educate

18   the   people     who    answer     it,    to    be    able    to

19   provide that information, if people do call

20   you, and I know that the new labeling is not

21   on the product quite yet, but it will be

22   shortly.




                           Neal R. Gross & Co., Inc.
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 1                  MR. CAMPBELL: It will be shortly.

 2                  DR.     LEONARD-SEGAL:     Do    you    know

 3   when that is?

 4                  MR. CAMPBELL: Around the end of

 5   the year.

 6                  DR. LEONARD-SEGAL: The end of the

 7   year?

 8                  MR. CAMPBELL: Yes, we're currently

 9   burning through old labeling inventory.

10                  DR.     LEONARD-SEGAL:        So,      you're

11   waiting for the next printing?

12                  MR.     CAMPBELL:      It's      the     next

13   printing, yes.

14                  DR.    LEONARD-SEGAL:      So,    is    it

15   possible for you to set up at your shop, with

16   the people that usually answer questions, for

17   those   people    to    provide    them    with    some

18   information about the phase-out, so that they

19   can   answer    those    questions     in an informed

20   manner?

21                  MR.     CAMPBELL:      I    think       it's

22   certainly   something      we   can    consider       and




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
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 1   discuss.      The hotline is for any information.

 2    So, that's information that's going to have

 3   to be available to the individuals who answer

 4   that line, and we'll see that it is.

 5                    DR. LEONARD-SEGAL: Okay.

 6                    DR. CHOWDHURY: I just want to ask

 7   one follow up question, maybe the same exact

 8   question that was asked a minute ago.

 9                    I think one of the things that

10   we're coming back and hearing multiple times

11   is the right place where the information comes

12   in,   as   the    initial   starting   point   is   the

13   product itself, who is buying them, they can

14   read it, and we hear it will be put out on the

15   product with the next printing cycle and can

16   you give us some idea, exactly when on the

17   shelf, those information can show up?

18                  MR. CAMPBELL: Based on what I know

19   about   the    distribution    patterns   of   this

20   product, it would be in the first quarter of

21   next year.

22   If we start labeling in December or January,




                         Neal R. Gross & Co., Inc.
                                202-234-4433
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 1   it would be by the end of first quarter, it

 2   would be out in the field.

 3                 CHAIR SEYMOUR: Dr. Hendeles?

 4                 DR. HENDELES: What about Bronkaid

 5   Mist?   That's your competitor, right?

 6                 MR.     CAMPBELL:     Yes,     I    have   no

 7   information on them.

 8                 DR. HENDELES: So, they're not at

 9   the   table   and     they   sell    a     good    bit   of

10   epinephrine, as well.

11                 MR. CAMPBELL: Jake?

12                 MR. LIAWATIDEWI: Bronkaid Mist is

13   no longer available.

14                 CHAIR    SEYMOUR:      I   think     there's

15   just one product now on the market.

16                 MR.    CAMPBELL:      It's    probably     a

17   product we made under private label and when

18   we bought the Primatene trademark, we removed

19   all the private label materials.

20                 CHAIR SEYMOUR: Dr. Parker?

21                 DR. PARKER: So, is this labeling

22   available in any primary language, other than




                         Neal R. Gross & Co., Inc.
                                202-234-4433
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 1   English, for sale in the United States?

 2                  MR. CAMPBELL: Not at this time.

 3                  DR. PARKER: Okay, with any plans

 4   in the future to make it a primary label in

 5   Spanish,     rather    than   in   English,   for    the

 6   United States?

 7                  MR.     CAMPBELL:     We   don't      have

 8   current plans to do that.

 9                  DR. PARKER: Okay, is this product

10   for   sale   in   primarily    Spanish    speaking

11   countries, with a label that's in Spanish.

12                 MR. CAMPBELL: It's sold only in

13   the U.S.

14                 DR. PARKER: Okay, sold only in the

15   U.S., okay.    So, this label is very confusing

16   to me, and to many people, I would imagine and

17   because there's so much information on it and

18   the reason you can't tell me on this, that

19   it's no longer going to be available, and by

20   the way, this is what people keep, they throw

21   this away, usually, they take it out of the

22   box and you throw it away, and this, you might




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
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 1   get out of the bottom of the box, but you

 2   might not, because it's kind of crumpled up

 3   down in the bottom, you know, it's down on the

 4   bottom and then this is on top of it.

 5                 This is what you want because you

 6   can't   breathe,    or     rather,      you've      having

 7   trouble breathing, and so, this is what you

 8   hang on to.

 9                 And so, it concerns me that the

10   fact that it's going to be discontinued, that

11   there's not enough space on here and I would

12   argue that may be the most important thing

13   that's going to be on here, and so, I think

14   there should be some consideration of that.

15                 I      would         also          encourage

16   consideration, if you really want to get a

17   message out, adding a stick on label on red

18   that    says,       "This        product         will        be

19   discontinued,"     would    be    the    way     to    catch

20   someone's   attention      and    to    put    it     on   the

21   primary side of the box and then to also put

22   it on what people are actually going to be




                        Neal R. Gross & Co., Inc.
                               202-234-4433
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 1   using.   You could do a wrap-around on here or

 2   something.    This could be tested and sort of

 3   worked out.

 4                 But if you really want to inform

 5   people, that's why I'm so curious to see what

 6   got approved. Because it's very hard to find a

 7   lot of information, find something specific

 8   and look for it, and then try to make it

 9   actionable.

10                 So,    I   think   from   the   patient

11   standpoint, here again, working with them, but

12   if we're sure it's going off the market in

13   December 2011, and that is our number one

14   message, that needs to be, you know, totally

15   apparent on this, not just on this, and if

16   you're going to put it on here, it's got to be

17   on the container front that faces out on the

18   shelf, because that's what you see when you

19   look at the shelf, and a lot of people can't

20   even read these fonts.

21                 So, I think it's really important

22   to get it down to that level.




                         Neal R. Gross & Co., Inc.
                                202-234-4433
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 1                  MR. CAMPBELL: You'll see when you

 2   look at the labeling I sent you earlier today,

 3   that in fact, it is a red bar on the primary

 4   display panel with type in white, it's very

 5   legible.   It goes right on there and there's

 6   also, on the insert, it's done in red, so it

 7   stands out.

 8                  DR.    PARKER:     Could   you    consider

 9   putting something on the product ?

10                 MR. CAMPBELL: We can discuss it.

11                 DR. PARKER: That would be great.

12                 DR.      LEONARD-SEGAL:       I     have     a

13   question   for   Mr.     Campbell.        Is    there    any

14   concern that once consumers know this product

15   is being phased out, that they would hoard it,

16   stock up on 50- 100, and that that would be of

17   any concern?

18                 The second question is, can they

19   order it online?

20                 MR.     CAMPBELL:    No,    they    cannot

21   order it online.       It is somewhat of a concern,

22   that people might hoard.        We did see some of




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
                                                                 Page 255
 1   that    as   albuterol     went   off     the   market,

 2   albuterol CFC.

 3                  DR. LEONARD-SEGAL: I didn't know

 4   if there was any kind of education message

 5   that might go along with that hoarding, that

 6   we should get out to the consumer, like, be

 7   careful not to have expired or products on

 8   your shelf too long or don't store it and so

 9   on and so on.

10                  I didn't know if that was anything

11   that we need to consider.

12                  MR. CAMPBELL: I think it would not

13   be a bad idea, to consider that, and it's

14   possibly something we can do, when we set up

15   the addition to our website.

16                  DR. HENDELES: What is the shelf

17   life of Primatene Mist?

18                  MR. CAMPBELL: It's 24 months.

19                  CHAIR SEYMOUR: Well, I think we

20   have already moved onto messages.           So, let's

21   kind of formally move to that section and talk

22   about   what    messages    we    think    need   to   be




                       Neal R. Gross & Co., Inc.
                              202-234-4433
                                                                 Page 256
 1   conveyed, and there's been some things tossed

 2   around, but let's maybe try and get a list of

 3   messages, so that we can prioritize, because

 4   it sounds like, from Dr. Parker, we only want

 5   to have a few key messages for this.

 6               Dr. Hendeles?

 7               DR.    HENDELES:    I    like    the    other

 8   suggestions, that the first one should be,

 9   this is no longer going to be available.            The

10   second one is that you could contact a health

11   care provider, and I would ask for a third

12   one, and that is that this type of medicine

13   alone is not sufficient for many types of

14   asthma or somehow, communicate the idea that

15   this is not a bronchospastic disease.         This is

16   an inflammatory disease in the airways.

17               So,     I   know,       you're    frowning

18   because of the length of that.

19               DR.    LEONARD-SEGAL:      I'm   smiling.

20   I'm trying to think of how to do it.         It's

21   very complex.

22               DR. HENDELES: Right, but if you




                       Neal R. Gross & Co., Inc.
                              202-234-4433
                                                                        Page 257
 1   could get it down to one sentence, something

 2   to the effect that, this type of medicine

 3   alone is not sufficient for asthma.

 4                    DR. LEONARD-SEGAL: So, would you

 5   rather see that than to urge people to start a

 6   relationship with a physician, to treat their

 7   asthma?

 8                    DR. HENDELES: I listed it as the

 9   third,     the    second    bullet    is    to    contact      a

10   health care provider.

11                    CHAIR SEYMOUR: So, I take it, you

12   would      not         recommend      any        therapeutic

13   alternative in the message?

14                    DR.    HENDELES:    Correct,      I   think

15   that should be up to the health care provider

16   that they seek.

17                    DR. PARKER: I would just add that,

18   and I think it's very clear, from everyone,

19   that we suspect and we know that            at least a

20   third or more of the users are people who are

21   poor, or who have trouble with access or with

22   payment.




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
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 1                  We're not sure about the rest, but

 2   at least a third, as we've heard, sort of

 3   demographically,         but      I     think      in    the

 4   recommendations        and   in    the       public   health

 5   message, I mean, what's very clear to me is,

 6   we really want to make sure that the best

 7   possible      clinical       care       is      provided      to

 8   everyone, regardless of their income.

 9                  I mean, there are access problems

10   and there are problems with payment, but you

11   know, we don't want to stratify the care that

12   we recommend for bronchospastic disease, based

13   on your income.       I mean, we want the best care

14   for everyone and we want to figure out how to

15   use   the    system    to    get evidence-based good

16   practice, good care to everyone, regardless of

17   their income, and I think it's very clear from

18   the clinical practice, that the best approach

19   to treating the bronchospastic disease is the

20   one   that    you're    saying        that    they'll   get

21   through a clinical encounter and an evaluation

22   that puts them on the right track to medical




                       Neal R. Gross & Co., Inc.
                              202-234-4433
                                                                         Page 259
 1   therapy.

 2                  CHAIR SEYMOUR: Dr. Reidenberg?

 3                  DR. REIDENBERG: I think one of the

 4   things that Ruth said repeatedly was it had to

 5   be actionable.

 6   I agree completely with what the best care is.

 7    The   question      really     is,    in     2009,     in    the

 8   United States, is it actionable for everybody

 9   with asthma?

10                 We    know    that      if    you   look       at

11   populations    who      don't   see     doctors,      it's

12   substantially young men.          Women will go see a

13   doctor more than men.         Older people, more than

14   younger people.      Children will be taken by

15   their parents, and when we look at the age

16   distribution       of     where       asthma      is,        it's

17   children, adolescents and young people.

18   So, that I agree completely with the goal,

19   that every other physician here has stated,

20   with respect to what asthma care ought to be.

21                 The    problem      I    have    with     the

22   patients that I care about is that this isn't




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                         Page 260
 1   an actionable item available for many of them

 2   for various reasons, and to say that the only

 3   messages we need to get across are what is the

 4   very best care, is really saying that if you

 5   don't      get        this,     we     have        no   other

 6   responsibility as a society, and I think we

 7   need to decide that, as a conscious decision,

 8   not by default.

 9                    CHAIR SEYMOUR: Andrea?

10                    DR. LEONARD-SEGAL: Yes, I mean, I

11   think that, you know, again, our main issue

12   here is that this is going off.                Perhaps Mr.

13   Campbell's group will provide a direct to OTC

14   viable HFA inhaler before 2011, the end of the

15   year, I don't know.

16   I don't know if some of the albuterol folks

17   are   going      to    be     interested      in    pursuing    a

18   switch before that time and whether that would

19   actually    happen       or     not,   in     terms     of   the

20   application process.

21                    There are a lot of possibilities

22   of things that could happen over the next two




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
                                                                   Page 261
 1   years.        But saying that none of them did,

 2   we're in this position where this is going

 3   away and we are not going to change that.

 4   That can't change under the Montreal Protocol

 5   and Clean Air Act.

 6                      I guess that one of the things

 7   that      I    keep   hearing   over   and    over   again,

 8   whether it's Rx or OTC, and if we're not going

 9   to have a viable OTC product, but even if we

10   were, and if everyone were going Rx or even if

11   they weren't, across the board, it sounds to

12   me   as       if   people   still   can't    use   these

13   inhalers, period.

14   So, is one of the messages that we want to say

15   is that, these are hard to use.             You have to

16   be sure you can use them.           If you're going to

17   see a doctor, be sure to ask your doctor to

18   show you how to use the inhaler, so that when

19   you can't breathe, you can get relief.

20   I keep hearing this theme over and over and

21   I'm wondering if this is message number three.

22    I'd like some comments on that.




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 1                 DR. PARKER: It's actually even one

 2   step beyond that, from a couple of studies

 3   that have looked at this.

 4                 It's not just, make sure someone

 5   shows you how to use it.     It's actually,

 6   demonstrate your use to someone, who knows

 7   correct use, to make sure you're doing it

 8   right.    That's a huge step.

 9   It's very different to show someone and say,

10   do you understand how to use this?       Have you

11   got it?    I guarantee you, everything is fine.

12   Everybody has got it.      Everything is okay.

13   It's very hard to admit and you cannot know

14   that you don't know it.     So, the real message

15   to the public is more, demonstrate using it,

16   to the person who is prescribing it.       It's

17   really your prescriber, even, you know.

18                 The pharmacist should know correct

19   use of an inhaler, as well.       But let's ask the

20   others    here.    Who   should    actually   verify

21   correct use of an inhaler? If you had your

22   druthers, who do you want to verify that it is




                       Neal R. Gross & Co., Inc.
                              202-234-4433
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 1   being correctly used?       If you could put out

 2   the public health message and have people hear

 3   it, who should be verifying that I know and

 4   that my use is accurate?

 5                 DR.    HENDELES:    Well,    I've    spent

 6   well over 30 years trying to teach pharmacists

 7   to do that and through the National Asthma

 8   Education Program, we had a recommendation for

 9   how pharmacists could improve asthma care and

10   through the American Society of Health Systems

11   of Pharmacists.

12   We had videos to pharmacy schools and none of

13   that   has   worked,    because   they're too busy

14   filling prescriptions.

15                 And so, while ideally, it should

16   be the pharmacist and that should be part of

17   dispensing, it in fact, over the years, has

18   not turned out to be that and it also has not

19   to be that in the primary care physician's

20   office, and with mail-in, there's no chance.

21                 One other thought I had is, we're

22   talking   about     this   inhaler   and   do     we   all




                         Neal R. Gross & Co., Inc.
                                202-234-4433
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 1   realize this is an antiquated formulation, an

 2   antiquated way of delivering an inhaled drug,

 3   and you know, it's really a pity that in this

 4   country, that the switch and the replacement

 5   of the CFC went to HFAs, when in the rest of

 6   the world, they're using dry powder inhalers

 7   and in my experience, when I teach a patient

 8   how to use a turbuhler, a diskus, etcetera,

 9   they come back three months later, using it

10   correctly.

11   I just don't have the problems. Once you teach

12   somebody with a dry powder inhaler, they seem

13   to be able to reproducibly use it.

14                CHAIR SEYMOUR: Dr. Liu, did you --

15                DR. LIU: You know, what I'm afraid

16   of, in terms of hearing what other people are

17   saying, is that you're trying to deal with

18   issues   related    to   asthma   management   in

19   general, in a situation where you're basic

20   message is, this is going off, and I think,

21   just keep it simple, because these issues, you

22   know, the reason you're getting this over and




                        Neal R. Gross & Co., Inc.
                               202-234-4433
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 1   over    again,    are    these    disease      management

 2   issues, relating to adherence and applying

 3   people's ability to understand and perform

 4   something that is not just taking a pill.

 5                   In   a   direct    answer      to   your

 6   question, I think it's basically anybody who

 7   has been properly trained to observe and teach

 8   and use these, it doesn't take any particular

 9   degree.    It just takes the experience and

10   dealing with people and watching all the crazy

11   things people can do with these.

12                   I mean, you know, you saw a video,

13   but    people    don't   even     take   the    cap   off

14   sometimes.      I mean, it's an amazing array, but

15   those are the outliers.          I mean, in general, I

16   would say, people, especially with the beta

17   agonist, as I was saying before, they figure

18   out that this helps them and they take enough

19   of it to get some effect.

20                   So, even though you're hearing a

21   lot of these issues related to inability, I

22   don't think that should be the message from




                          Neal R. Gross & Co., Inc.
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 1   this, because these are just issues related to

 2   use of inhalers and devices, spacer devices,

 3   the whole thing that have to do with dealing

 4   with dealing with a respiratory drug that has

 5   a sort of unique problems or issues.

 6               CHAIR SEYMOUR: I think that's a

 7   good point and to maybe bring us back on

 8   target here.   But I think Ellen had another

 9   question.

10               DR. LEONARD-SEGAL: I just wanted

11   to say, it doesn't mean that we couldn't do

12   another campaign that focuses on adhering to

13   your medication.

14               DR.    LIU:   Absolutely   not,   but   I

15   mean, as I said, these are issues that have

16   been dealt with, with the education program

17   and these are emphasized over and over again.

18   I mean, and a lot of these things really have

19   to do with an interface and the time between

20   the patient and the physician or the office or

21   the health care provider.

22               DR. LEONARD-SEGAL: Right, my point




                       Neal R. Gross & Co., Inc.
                              202-234-4433
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 1   is     that   we    can     still    address        those   as     a

 2   separate education effort and not include it

 3   as one of the third messages and to dilute the

 4   concept of, this is being phased out message,

 5   which I think maybe we're agreeing is more of

 6   the focus here.

 7                   DR. LIU: There is an awful lot,

 8   just in a conceptual sort of way, already

 9   happening, in terms of differentiating asthma

10   as a disease of smooth muscle. You see the

11   ads.      I    mean,      and   it's    because       we're

12   targeting,          you      know,         smooth       muscle

13   contraction, and inflammation as two separate

14   and    manageable      components       of      a   complex

15   disease,      and    that    message       is    getting     out

16   there.

17   So, I think that the idea, you see it on

18   television, in the ads, you know, bronchospasm

19   and    inflammation,        and     that    sort     of,    is

20   trickling down.

21                   And so, if you wanted to add a

22   message like Les was saying, about, this is




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
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 1   only a bronchodilator or this is only for a

 2   certain problem, and emphasizing              this does

 3   not manage asthma, is a second bullet point,

 4   and then see your physician.

 5   I   think    that    there    may     be   sort    of    an

 6   educational thing you could take advantage of,

 7   to try to tell people, look, this only deals

 8   with symptoms and your underlying problem may

 9   go untreated.

10                  CHAIR SEYMOUR: So, I think to kind

11   of move onto the next part of the message

12   question,     I    didn't    really    hear    anybody

13   recommend any therapeutic alternatives, any

14   specific     therapeutic      alternatives        in    the

15   message.

16   And I just want to make sure that people have

17   a   chance    to    comment    on that, specifically

18   because there was some discussion, there are

19   other OTC products available for asthma and

20   should   the      recommendation      be   to use these

21   products or not?

22                  DR. LIU: Well, the short answer, I




                         Neal R. Gross & Co., Inc.
                                202-234-4433
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 1   think,   is    no.      Nobody   has    said   anything

 2   because, and as you heard, nothing else really

 3   is effective.

 4                  DR. CHOWDHURY: It's actually good

 5   for us to hear the `no' pretty loud and clear,

 6   so that we are pretty confident that we are

 7   not recommending anything that -

 8                  DR. PARKER: No.

 9                  DR. REIDENBERG: A loud and clear

10   no.

11                 DR. HENDELES: There's no question

12   that even if you take albuterol orally, that

13   it has a poor therapeutic ratio.          I mean, it

14   has a lot of side effects for the same degree

15   of bronchodilitation .

16   And so, there really isn't any place for oral

17   agents, in the appropriate therapy of asthma,

18   in my opinion.

19                 DR. PARKER: I also have concern,

20   and this is not personal.        I appreciate your

21   being here, because it's really important.

22   You're   key     to      figuring      this    out   and




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
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 1   understanding what to do, from a public health

 2   standpoint.

 3                  I think it's really important for

 4   Jane and Joe, consumer/patient, not to feel

 5   like everything is going to be just fine,

 6   because something else is coming back on the

 7   market     over-the-counter,      that   I   can   use

 8   instead of this.

 9                  I don't think that is the best

10   care and the best approach to the management

11   of wheezing, bronchospasm, tightness of chest

12   or shortness of breath and I think it would be

13   more than a missed opportunity.          I think it

14   would be a mistake, for that message to end up

15   in the minds of Jane and Joe, when they walk

16   in the drug store.

17   So, I think that that's actually a really

18   important    point,    that   I   think I'm hearing

19   consensus on, that for the symptoms that we

20   assign a clinical diagnosis of bronchospastic

21   disease,    reactive    airway    disease,    COPD,      I

22   mean, the list can go on.




                       Neal R. Gross & Co., Inc.
                              202-234-4433
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 1                     When these symptoms are present,

 2   they need to be evaluated by a physician or a

 3   health practitioner with expertise in making

 4   an accurate diagnosis and getting that person

 5   to appropriate treatment.

 6   Appropriate        treatment       for   those   symptoms

 7   really is not taking the alternative inhaler

 8   that may appear on the market for this.                 Now,

 9   I   know    that's     not    the     purpose    we    were

10   convened, but I think as we're staging the

11   public health campaign about the messages,

12   that we want to be very clear, at least that

13   our advice is that message is not wait and see

14   what else comes available over the market.

15                  DR. LEONARD-SEGAL: It has been our

16   policy     over    time,     not    to   refer    to   other

17   products, OTC products, when we're labeling or

18   talking about another OTC product.               We have

19   not done that.

20                  CHAIR SEYMOUR: Dr. Schmidt?

21                  DR.    SCHMIDT:       I   just    wanted    to

22   comment that I think part of our disadvantage




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
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 1   in not knowing who is purchasing the Primatene

 2   Mist now, is that we don't know why they're

 3   purchasing it.

 4   You     know,   we're    assuming     they're   having

 5   wheeze,     cough   and    shortness     of breath and

 6   whatever.

 7                   If we knew that most of them did

 8   have asthma, then your message could focus on

 9   that, you know, and get them into the doctor's

10   office, using that as kind of the hook.

11                   If you have any of these symptoms,

12   it could be asthma.        You know, you need to see

13   a doctor.

14                   But I'm wondering, why do people

15   buy it?    Do they just have a cough? I mean, a

16   cough    can    source    from   so   many   different

17   diseases. So, it is a disadvantage, not to

18   know that, in terms of trying to figure the

19   message because if we're limiting the message

20   and if we knew that the majority were possible

21   asthmatic or asthma patients, then I can see

22   emphasizing that a lot more and in the plea to




                         Neal R. Gross & Co., Inc.
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 1   do to the doctor, but I guess we don't know.

 2                CHAIR SEYMOUR: Dr. Chowdhury, do

 3   you still have a comment?    Dr. Reidenberg?

 4                DR. REIDENBERG: Yes, we know that

 5   inhaled beta agonist is good treatment for

 6   exercised induced asthma.

 7   Les talked about the college students taking

 8   it.   The two publications I was able to find

 9   and review in my presentation, suggested that

10   people   that     were   using   this,   were

11   appropriately selected.

12   I know that the poor children in New York have

13   been diagnosed by a physician.    So, we're not

14   talking about self-diagnosis.    We're talking

15   about management of chronic disease.

16   The poor children in New York that we were

17   looking at, should be on steroids as well.

18   The beta agonist are insufficient.    They were

19   not getting them, even though they had been

20   seeing doctors.

21               For the ones in the literature and

22   the college students, apparently, this was




                       Neal R. Gross & Co., Inc.
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 1   appropriate treatment for what they had.

 2   I   can't   tell    whether      they   had    physician

 3   diagnosis    or    not,    but    I'm   not    aware    that

 4   college students, as a class, don't get to see

 5   doctors.

 6                 So,    I    think    that   we    can    be   a

 7   little more selective and less broad with our

 8   brush, as to what kind of people we're aware

 9   of using short acting beta agonists, as their

10   only medication appropriately.

11                CHAIR SEYMOUR: Dr. Parker?

12                DR. PARKER: I just want it to be

13   clear, so that you understand this.            But the

14   expanded labeling of this product, that FDA

15   mandated, had to require, and it's in here,

16   just so you know, "Do not use unless a doctor

17   said you have asthma."

18                So, that's in the mandate. That's

19   in the required current labeling and that's

20   why I think it's a very relevant thing to, you

21   know, make sure that that's done.

22                CHAIR SEYMOUR: Dr. Hendeles?




                         Neal R. Gross & Co., Inc.
                                202-234-4433
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 1                DR. HENDELES: I just want to clear

 2   up, from my experience in Florida, we have

 3   about 15 new patients each week that come to

 4   our clinic and I can't remember in years,

 5   where a child has come, using Primatene Mist,

 6   in contrast to the college students.

 7                So, I don't think the use of this

 8   product is very big in children.

 9                DR. CHOWDHURY: I just want to go

10   back to a comment that Dr. Parker made, maybe

11   two comments back, regarding the alternate

12   treatments, which we all heard loud and clear,

13   as other bronchodilators and the message is to

14   see a physician and have the physician make a

15   proper decision for treatment.

16                I just also want to refer back to

17   what our colleague from Armstrong has stated

18   earlier,   about    having   a   possibility of an

19   alternate non-ODS propelled epinephrine as a

20   replacement product, possibly for 2011.

21                I        also        mentioned       that

22   reformulation    of   this   product   is   pretty




                        Neal R. Gross & Co., Inc.
                               202-234-4433
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 1   challenging and for the purpose of the rule,

 2   we have gone forward with the presumption that

 3   an alternate may not be there.

 4                 So, the comment, I just wanted to

 5   make sure I heard you say correctly, or if you

 6   could repeat it, what you said, if there is

 7   one, as a non-ODS, alternate epinephrine, how

 8   should we be viewing that?

 9                 DR.    PARKER:      I    recognize    that

10   that's slightly tangential to the fact that

11   this is coming off, but I think it's very

12   important from a consumer standpoint, from a

13   patient standpoint, to recognize what we have

14   heard   soundingly     about     the     best    available

15   treatment,    not    being   to       take an over-the-

16   counter product for asthma.

17                 I mean, that's actually a very big

18   deal,   because     you   have    to     be    diagnosed.

19   According    to   this,    do    not     use    this.      Of

20   course, you might not be able to read it. I

21   don't think people, most of them, read this

22   anyway.




                         Neal R. Gross & Co., Inc.
                                202-234-4433
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 1                    But anyway, it is on here and it

 2   was mandated, do not use unless a doctor said

 3   you have asthma and so, I think that's a very

 4   big point for future consideration because I

 5   think what I would say and what I'm hearing

 6   is, if you have asthma or if you have these

 7   symptoms that we're talking about, with chest

 8   tightening, shortness of breath, whatever the

 9   words end up being that you learn, because you

10   listen to people tell you what the words are,

11   but    wheezing,    whatever     it   is,    these      are

12   symptoms that need to be under the management

13   and guidance of a medical practitioner and

14   they    should    not   be    self-medicating       and

15   diagnosed in treating asthma.

16                 Yes, you heard me correctly.

17                 DR. LEONARD-SEGAL: Can I follow up

18   on that? From an OTC perspective, recognizing

19   that the world isn't perfect.

20                 What       generally,         are      asthma

21   patients    told    when     they   go   into     see    a

22   physician, they get a prescription, they have




                         Neal R. Gross & Co., Inc.
                                202-234-4433
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 1   it,     they    maybe    travel,    they   lose    their

 2   albuterol inhaler or their suitcase doesn't

 3   arrive     or    something    and    they develop some

 4   bronchospasm?

 5                    Are they told what to do?         Should

 6   they be immediately running to an emergency

 7   room somewhere in a foreign city or what's the

 8   message?       What is the place in that situation,

 9   potentially for OTC asthma treatment? I just

10   bring up contingencies, when we think about

11   these     things        because     you    know,    the

12   conversation is, I think, a very important one

13   and in the OTC world, we always worry about

14   the perfect getting the better of the good, so

15   to speak.

16                   And so, I just wonder where we are

17   because certainly, we have rule making that

18   says, you know, was recommended by panels of

19   experts, albeit a long time ago, that asthma

20   like this, mild asthma, mild, intermittent or

21   however the language would fit into the new

22   category of terminology, newer category of




                         Neal R. Gross & Co., Inc.
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 1   terminology, is an OTC indication.

 2                  We    don't    have    back    the      adverse

 3   event reports that would have triggered us to

 4   remove this product just because of safety

 5   concerns.

 6                  We've heard today that there are,

 7   at least I think I heard, please fix me if I'm

 8   wrong, but I think that what I learned today

 9   was that there are many or maybe more problems

10   seen   with    the    albuterol      inhaler,     to    some

11   regard,   in    terms    of   over-use       or   problems

12   ultimately.

13                  There     is    a      population        that

14   benefits from this product, according to your

15   slide, compared with the albuterol inhaler.

16                  So, I want to just call us back

17   and think about, you know, where we are going

18   here and what the purpose is.           This is again,

19   our purpose here is to inform about a product

20   going off the market because of the ozone

21   layer.

22                  So, I think we shouldn't get too




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
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 1   far askew.     But as we're talking in general

 2   about the perfect being the enemy of the good,

 3   I just want to remember what the good is and

 4   see if I can understand what the good is.

 5                  CHAIR SEYMOUR: Dr. Liu?

 6                  DR. LIU: I think, depending on how

 7   old those panels are, there really has been a

 8   major paradigm shift in asthma in terms of it

 9   being initially a brochospastic disease and

10   treated with epinephrine and that was what was

11   earlier, this history of this, you know, I

12   mean, I don't necessarily need to go through

13   it,   except    to    say   that    this    inflammatory

14   component    is   probably     something      that    has

15   really taken prominence over the last 20 or 30

16   years.

17                  So, anything that's sort of like

18   before that, because we used to recommend, I

19   don't know about Les, but I used to recommend,

20   or a lot of people recommended regular use,

21   every four hours, of an inhaled brochodilator.

22                  Well,    I   mean,    some    people    may




                          Neal R. Gross & Co., Inc.
                                 202-234-4433
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 1   still do that, but that's certainly not the

 2   recommendation would be, because part of the

 3   goal of asthma management now is control and

 4   preventing episodes from happening, so that

 5   somebody doesn't have to rescue themselves.

 6                    So,    that's     the      background,      I

 7   guess, of the understanding of this.

 8                    I    don't     know   if      you   wanted      a

 9   direct question to this            contingency thing,

10   but depending on how severe this episode is

11   and who it is, I mean, somebody who has a

12   regular need for bronchodilator, adjusts their

13   life around having it available, which from a

14   specialist point of view is not a great thing

15   because it means they're unstable and they're

16   having    more       symptoms    and     may    need   better

17   therapy.

18                   Someone who has very intermittent

19   disease, and this is the danger that you get

20   into,    they    may     be   able     to    just    treat

21   themselves, you know, maybe every few weeks or

22   every few months.         They have an episode and




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
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 1   they take the bronchodilator, they feel better

 2   and they're fine.

 3                    But anybody who really has asthma,

 4   has    potential     risk   for   life    threatening

 5   episode, depending on their exposure or an

 6   infection or something in a current illness.

 7   It may make them have an episode that's severe

 8   enough to wind them up in the hospital or

 9   emergency care and that sort of thing, and

10   that's sort of what we're talking about, is

11   the    concern      that    instead      of   getting

12   appropriate therapy without some professional

13   input, that this person will continue to take

14   this   bronchodilator,      you   know,    every   four

15   hours or every two hours and I mentioned to

16   somebody, a study where in conjunction with

17   the slide that was shown before, the average

18   number     of     inhalations     for     hospitalized

19   patients    at    Hopkins   and   Bayview, this was

20   about maybe 20 years ago now, was almost 50

21   puffs of a bronchodilator.

22                   So, that's two puffs every hour,




                         Neal R. Gross & Co., Inc.
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 1   on average and then there were some people

 2   that used hundreds.       They would go through a

 3   canister.

 4                  So,    that's    the   extent     of    the

 5   problem that you're dealing with and people

 6   get sick.     They want to feel better.          They

 7   treat   this    and    then    they   may     delay    more

 8   appropriate treatment for the disease.

 9                  So, I don't know if that's the

10   answer to your question.        I think I've gone on

11   for longer, but, you know.

12                  DR.    LEONARD-SEGAL:     Well    it's    a

13   piece   of    the    answer.     I    mean,    but    these

14   extreme patients are not the ones that are

15   really targeted OTC and so, again, I ask, you

16   know, what is the potential role, following up

17   on Badrul's question earlier?

18                  CHAIR SEYMOUR: I think I'd like to

19   try and bring it back to the discussion we

20   were having about the message, and I think

21   we've   had    several    statements     made    and    I

22   haven't heard any new statements, in terms of




                          Neal R. Gross & Co., Inc.
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 1   messages.

 2                   So, I think this is very important

 3   that the agency has clear idea of what message

 4   we think should be conveyed.

 5                   So,    I'd    like    to     summarize    the

 6   several items I've heard and then kind of

 7   close out the message part of the discussion,

 8   so we can move on.

 9                   So, I heard that clearly, the main

10   number one thing we need to convey is that

11   this   product    is     no   longer       going   to    be

12   available after such and such a date, and that

13   the secondary message would be to refer to a

14   health   care    provider       of    some    sort,     for

15   evaluation and management and the tertiary

16   message could be that this medicine alone may

17   not be sufficient for the treatment of asthma.

18                I heard clearly that we should not

19   be   recommending       any   specific       therapeutic

20   alternative.     I clearly know that we should

21   not be recommending the available OTC asthma

22   alternatives     and     that    to    keep the message




                           Neal R. Gross & Co., Inc.
                                  202-234-4433
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 1   simple.

 2                     And so, I think that's what I took

 3   away from this discussion.              Unless there's

 4   anything        new,   I'd     like    to     close   out    the

 5   message part of the discussion.

 6                     DR. PARKER: The only thing I want

 7   to add is, the evidence of the message, but

 8   combined, side-by-side, equally important is

 9   the audience you're trying to reach and their

10   input and understanding that message, and FDA

11   finding a way, to create a couple of focus

12   groups,     a    couple      of   panels      of   people     who

13   actually use these products, where you sit

14   with them and you discuss with them and you

15   talk with them and say, "Here is the essence

16   of   what    we    really      want     to    make    sure    we

17   understand."

18                    Listen, put that back and forth

19   and go around and around, you know, because

20   here   it        is,     how      do     we     assess       the

21   comprehensibility?             You     get    it   from     the

22   experts, the people who are using it.




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
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 1                 So,    you    take    that    content,     you

 2   work with the people, you know, you cannot

 3   leave that out, and that's done so often, and

 4   that's why we end up with web-pages full of

 5   stuff that people can't understand.

 6                 CHAIR SEYMOUR: And so, part of the

 7   message question, I think you addressed bullet

 8   three and you had a slide telling, kind of

 9   outlining how this process be performed.

10                 Does anyone have any comment on

11   other   groups       that     may     be    willing      to

12   collaborate with the FDA on this process or

13   any ideas about that?

14                 MS. SANDERS: Are you asking for

15   people from here as well?

16                 CHAIR SEYMOUR: I think we'll take

17   input from the audience as well, because this

18   is something where we want information and

19   ideas on who we can collaborate with in terms

20   of   this.     Could    you    come    to   use    the

21   microphone?

22                 MS.    SANDERS:      Certainly,     allergy




                         Neal R. Gross & Co., Inc.
                                202-234-4433
                                                                       Page 287
 1   and    asthma     network,      Mothers    of    Asthmatics

 2   would like to collaborate on this messaging.

 3                    About 13 years ago, we actually

 4   did focus groups for patients getting ready to

 5   go     through    the    transition      and    we    did    it

 6   actually with patients and with physicians.

 7                    I think it would be good to do it

 8   with not only the people who are using these

 9   drugs, but also, the people that they're going

10   to be turning to and when we look at those

11   videos, we see everything that happened in

12   those, you know, that was predicted in those

13   videos actually came to be, and I think you'll

14   find    the   same      thing    would    happen      if    you

15   conducted focus groups with patients.

16                    They're going to be angry, number

17   one, that there's a change to their inhaler,

18   because of the ozone.           They're angry about

19   that already.

20                    We   don't     make   changes       to    our

21   medication plans based on climate change.                   So,

22   they're going to be angry and they're going to




                           Neal R. Gross & Co., Inc.
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 1   be angry at FDA.      They're going to be angry at

 2   who ever is delivering the message, whether

 3   it's the pharmacist behind the counter of the

 4   physician.

 5                 So, you need to make certain that

 6   that's taken into consideration as well.

 7                 So,    we   have    some   experience      on

 8   bulletins and we'd like to, you know, share

 9   that with you.

10                CHAIR SEYMOUR: Thank you.          Anyone

11   else?   So,    I     think    let's   move    onto    the

12   products part of our question and so, during

13   Ellen's presentation, she presented a list of

14   products that we did for the albuterol phase-

15   out and also ideas of what we can do, in

16   general, the FDA with the types of media we

17   have.

18                So,     of   the    products    that    Ellen

19   presented and that the FDA can develop, which

20   ones may be the most effective, and we've

21   listed them up there.        They may be a little

22   bit difficult to read, but I can read through




                         Neal R. Gross & Co., Inc.
                                202-234-4433
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 1   them very quickly.

 2                  Audio     visual      prints,       public

 3   service     announcements,     exhibit      banners    and

 4   posters,       articles       for        consumers      and

 5   professionals,         fact    sheets,         brochures,

 6   questions and answers, stakeholder letters or

 7   blasts,      transit     advertisement,          internet

 8   banners, websites, audio podcasts and video

 9   new clips.

10                  Does anyone have any opinion on

11   what may be more useful than others?

12                  DR. PARKER: Ask 50 people who have

13   used the product, in the last year, that same

14   question.

15                  MS. FRANK: One thing I have heard

16   this morning and mentioned a few times was,

17   have something at the point of purchase, and I

18   know that's not on our list and a couple of

19   ideas   that    were   brought      up   was    somebody

20   mentioned a flag.      I don't know what a flag

21   is, but I know that I have seen what they call

22   shelf-talkers, where it's like a little thing,




                       Neal R. Gross & Co., Inc.
                              202-234-4433
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 1   the size of a check and you can rip off from

 2   the pad, that sticks to the shelf.

 3                  It's not something that we could

 4   do at FDA because it's costly, but it is an

 5   option that I know was mentioned and that

 6   maybe, would be a good option for point of

 7   purchase, just a suggestion.           I don't know who

 8   would do it.

 9                  CHAIR SEYMOUR: Dr. Hendeles, did

10   you have one?

11                 Let    me   ask   the    manufacturer,

12   because it seems as if you have the unique

13   opportunity.    You have the product.        You can

14   reach the patient at the point of sale.

15                 You've presented what you plan to

16   do,   which   is    the   new   labeling    that   has

17   information that the product is going away,

18   and also, are going to put some information on

19   your website.

20                 But    in   terms   of    other   products

21   that you could use to reach the consumer,

22   because you have the opportunity to reach the




                         Neal R. Gross & Co., Inc.
                                202-234-4433
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 1   person who is buying it, are there any other

 2   plans to develop communications for them about

 3   this phase-out?

 4                  MR. CAMPBELL: At this point, we

 5   don't   have    any     plans    to    develop    anything

 6   additional.     I'm certain we're taking in, what

 7   we're hearing here today and we'll take that

 8   back and discuss it with our senior management

 9   and possibly develop a plan.            But I can't

10   promise anything.

11                  CHAIR SEYMOUR: Dr. Schmidt?

12                  DR. SCHMIDT: This may be getting

13   into the dissemination part of it, but I'm

14   thinking the fact sheet could feed into some

15   of the networks at the local level, like the

16   coalitions,     local    coalitions      and     community

17   groups, and that's more word of mouth.

18                  So,      you      know,     and      social

19   interaction, then a product per say, from what

20   I'm hearing, I don't see a big blitz, I don't

21   see   the   transit     things    as    being     all   that

22   useful or, you know, it seems like much more




                          Neal R. Gross & Co., Inc.
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 1   needs to be much more targeted, and we don't

 2   know where the target is.

 3                  But in the poverty areas or low

 4   socio-economic        areas,        certainly       working

 5   through a lot of those local networks.

 6                  CHAIR SEYMOUR: Dr. Liu?

 7                  DR. LIU: In this day of fiscal

 8   responsibility, I just throw this idea out,

 9   that I really think that as the message, the

10   dissemination or the product, the critical

11   thing is this point of use and making the

12   labeling     prominent,    so    that     it    cannot      be

13   missed by the people that are buying this

14   product and making the message simple.

15                  Frankly,    that's      all     I    think    is

16   necessary, beyond, you know, sort of, which

17   will   get    attention,      when    you    make     this

18   announcement     that    this    is    going       off   the

19   market.       There    will    be    media     attention,

20   various other things.

21                  You      know,        if     somebody        is

22   interested, the place to contact, to get more




                          Neal R. Gross & Co., Inc.
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 1   information about these sorts of things, we

 2   don't know who is using this but to some

 3   extent, from my point of view, we don't need

 4   to know.

 5                 I mean, that's sort of an extreme

 6   statement, but what we need to do is, who ever

 7   is buying this product in the next year or

 8   two, get the message out that this is going

 9   off and what they should do about it, and

10   that's it, because I don't know that it's

11   going to help us, and be, you know, possible

12   to   gather       this   sort     of   comprehensive

13   information about who the audience is, and

14   frankly, even people that are, as has been

15   pointed out, that are sort of like, poor and

16   in the inner-city, and I don't think this is a

17   totally economic issue.

18                 I    think,   you   know,   this   is

19   something, I mean, people that are difficult

20   and have asthma in the inner-city, very often

21   have contact with the health care thing and I

22   don't think a lot of them are actually using




                        Neal R. Gross & Co., Inc.
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 1   the over-the-counter medication.

 2                  They're not necessarily even using

 3   the recommended medications, much less going

 4   and   buying    and       trying    to manage over-the-

 5   counter stuff themselves.

 6                  So,    all     I'm    saying     in    a    long

 7   winded way is, I don't think it has to be very

 8   complicated, I think if the manufacturer, you

 9   know, puts prominent warnings that this is

10   going to happen, on the canister and on the

11   package insert and on the outside, I'm not

12   sure what more you can do beyond that.                Maybe,

13   you know, something that would give you more

14   information on a separate sheet, because if

15   they wanted to read about what was going on,

16   inside the thing, they could do that.

17                  But    I    think    part   of    it       is   to

18   inform people that this is not going to be

19   available and that's it, for now.

20                  CHAIR SEYMOUR: Dr. Parker?

21                  DR. PARKER: The only other point

22   that you're making me think about, in terms of




                          Neal R. Gross & Co., Inc.
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 1   the simplicity and you know, making it real,

 2   but making it actionable, would be whether or

 3   not you could create a statement.

 4                  I don't have it in mind.       I have

 5   one in mind that I would work on and develop

 6   with some other people to see if it worked,

 7   but something that said, you know, "it's going

 8   off, contact your doctor or" and you would

 9   give   some    alternatives,      health   department,

10   community     health   centers,    Go   Local is out

11   there for lots of people that can give you

12   access to what the providers are, something

13   that gives you something you can hang on to.

14                  So, if the first word says `your

15   doctor' and you don't have it, what are some

16   other contact points, health departments, you

17   might work with HRSA, to see, you know, what

18   would they put on that list and also, you

19   know, Go Local is a pretty important resource

20   that was very useful for a lot of displaced

21   people in the hurricane.

22                  But you know, looking to see if




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 1   you could put some short phrase in there, that

 2   actually gives a couple of contact points for

 3   potential care, that would be an evidence-

 4   based approach to that medical condition.

 5                CHAIR SEYMOUR: I think we should

 6   probably, in the interest of time, move on to

 7   dissemination.     It sounds like there wasn't

 8   any specific recommendation for one particular

 9   product from FDA, but to try and keep it

10   targeted    and     we    can    take     that     into

11   consideration as we move forward.

12                So, in terms of dissemination of

13   the information, what are the best methods to

14   disseminate each message and the product and

15   what is the time line for dissemination, which

16   may be a question that we're very interested

17   in.   Dr. Hendeles?

18                DR. HENDELES: So, I've made notes.

19    I think there are four organizations that

20   probably have priority.

21                One         would       be          pharmacy

22   organizations that could publish this in their




                        Neal R. Gross & Co., Inc.
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 1   news   letters      and    there   was     an   effective

 2   dissemination of the withdrawal of albuterol

 3   and that did get to the pharmacist and the

 4   pharmacist     did        advise       people    who    were

 5   complaining,     and      reassured      them   that   the

 6   product   that      was    substituted      was safe and

 7   effective.

 8                 So, I think that's important and

 9   there are a couple of big ones.             Is there any

10   pharmacy organizations here, at this meeting?

11    Could you raise your hand, if you're with a

12   pharmacy organization?

13                 That     may    be   a    problem,   getting

14   them   involved        but     there's      a    national

15   association    of    chain     drug     stores and then

16   there's       the         American         Pharmaceutical

17   Association      and         between       those       two

18   organizations, they have listservs and news

19   letters and so, I think they would be very

20   important.

21                 I think pharmacy schools, there is

22   one organization, an association of colleges




                         Neal R. Gross & Co., Inc.
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 1   of pharmacy that could disseminate this to

 2   pharmacists who are going to go out           into the

 3   community, before they even get there.

 4                  The CDC has a network of public

 5   health departments in the country and they

 6   have an e-mail connection on them and they can

 7   get information out to every county health

 8   department in the country very quickly, and I

 9   think there is an organization within the CDC

10   that   has   an    interest   with      asthma,    that's

11   partnered with the national asthma education

12   program.

13                  DR.    SCHMIDT:    I    definitely    think

14   that would be an excellent one and that's the

15   indoor air group, environmental.           I forget the

16   exact initials.

17                  But a lot of these people are on

18   the    NAEPP      coordinating        committee,     so

19   certainly, you know, through our membership,

20   we can push the message out as well.

21                  DR.    HENDELES:    Because    at    least

22   where we live, that's where patients who have




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 1   no resources turn to, they go to the county

 2   health department for primary care, and then

 3   the last group are ED physicians and I think

 4   that's   already    mentioned,   they're   in   a

 5   position and they have national organizations

 6   and state and regional organizations and get

 7   them to disseminate that same information.

 8                CHAIR SEYMOUR: And before we move

 9   on, Dr. Reidenberg, do you have any comment on

10   the timing of this communication?

11                DR. HENDELES: ASAP.

12                CHAIR SEYMOUR: Dr. Reidenberg?

13                DR. REIDENBERG: Yes, I think Dr.

14   Liu hit it on the head, where we want a target

15   approach.   We don't know who the purchasers

16   are, but we know that they go to the point of

17   purchase to get it.

18                So, if we want to target a message

19   to the people using it, the only way now we

20   can focus it is to go to the site of purchase,

21   because that's where they are.

22                We have the labeling.    Once we




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 1   start talking to people about `consult your

 2   pharmacist',   my   concern   is,   whether   the

 3   pharmacist will be pushed to recommend other

 4   alternative over-the-counter medications and

 5   whether we really want that to happen, given

 6   what the options are.

 7               DR. HENDELES: None of my students

 8   would.

 9               CHAIR SEYMOUR: Dr. Schmidt?

10              DR. SCHMIDT: I'm wondering if Dr.

11   Hendeles has made a case for the athletic

12   directors at the universities, for the EIB?

13              DR. HENDELES: That's a good point.

14   Maybe the student health services as well.

15              CHAIR SEYMOUR: Any other comments

16   on dissemination?

17              DR. PARKER: I know the National

18   Consumer League has a large national campaign

19   related to adherence that they're looking at

20   and you might look to see whether or not they

21   might, you know, pick up something on this.

22              Consumer Reports would be another




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 1   one, you know, just sort of consumer based.

 2                   DR. LEONARD-SEGAL: I would like to

 3   go back to the ASAP recommendation.          It's been

 4   said     that     repeating     messages     is     very

 5   important,      to   make   them    get into people's

 6   heads.

 7                   I don't know how many times you

 8   have    to   repeat    them,   three,    four,    five,

 9   something like that, before people start to

10   notice that you've actually said something to

11   them and it sticks.

12                   So, the question would be, when

13   you talk about people putting information into

14   news letters, would you be encouraging these

15   different    associations      to   repeatedly     print

16   this information or is there a timing?            Is it

17   better to do it now and then again in October

18   2011?    I mean, what is the spacing of repeated

19   messages and the point of service issue, where

20   it's on the product. It will always be there,

21   every time someone looks at it, once it's on

22   it.    But what about the rest of this?




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 1                   CHAIR SEYMOUR: Dr. Liu?

 2                   DR. LIU: My feelings are probably

 3   becoming very obvious now.            Not very many

 4   people use this product.          It's very, very

 5   different      than    the    albuterol     switch     over

 6   because,    you    know,      that    was   an   essential

 7   product.    This is not an essential product.

 8                   And    so,    that    distinction,      you

 9   know, in terms of how you get the message out,

10   I mean, not that any of these ideas, but

11   you're not going to be getting the message to

12   the people that are using this drug, I mean,

13   frankly, because it's such a small number of

14   people and you know, I just think there's

15   going to be very limited utility in making the

16   message to all these different, I mean, beyond

17   saying that it's not going to be available

18   anymore.

19                  Whatever else you want to say, I

20   just   think    is,     you   know,    nice,     but   not

21   essential or, you know, even necessary.

22                  CHAIR SEYMOUR: Dr. Chowdhury?




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 1                DR. CHOWDHURY: I just want to make

 2   a quick comment about the word `not essential'

 3   because it is different meanings, different

 4   ways and how it is used.

 5                As for the Montreal Protocol goes

 6   and as for the CFR 2.125 goes, these are

 7   listed as essential products.         It will be

 8   removed from the list effective December 2009.

 9    We just have to be careful about the word,

10   because   many   of   us   in   the   room   here   may

11   actually conclude otherwise.

12                DR. LIU: Right, and I think that I

13   was being reasonably precise because you've

14   already decided that it's not and that's why

15   the date is set.

16                I mean, it's essential now, but

17   it's not essential in terms of the overall

18   scheme.   There are alternatives and I think

19   people should be seeing their doctors about

20   getting the alternative.

21                DR. CHOWDHURY: Thank you, correct.

22                CHAIR SEYMOUR: So, to follow up,




                      Neal R. Gross & Co., Inc.
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 1   just Andrea's question.    Any other comments in

 2   the timing of when we should try to roll out a

 3   campaign?

 4                 We heard one comment about as soon

 5   as possible. Are there any other opinions?

 6                 It will take a while to put it

 7   together.

 8                 DR. LIU: Well, we're hearing the

 9   delayed wing is going on, you know, at the

10   beginning of the first. I think that's plenty

11   of time.    I would say a year before is plenty

12   of time, before the end of the thing, I mean,

13   you know, because anybody that doesn't buy one

14   of these things more frequent than a year is

15   probably not too much of a concern in terms of

16   who you want to make sure is getting proper

17   treatment.

18                 So, you know, I mean, you know, if

19   the deadline is December 2011, then December

20   2010 would be fine as far I'm concerned, but

21   that's an opinion.

22                 DR. CHOWDHURY: I just want to pose




                      Neal R. Gross & Co., Inc.
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 1   a   question    maybe      in   that   regard   to   the

 2   manufacturer.

 3                  I mean, December 2011 is the end

 4   date and I think ideally, one should try to

 5   achieve the transition way ahead of time, so

 6   that nobody is scrambling towards the end,

 7   now, what do I do?         Now, what do I do?

 8                  So, with that intent, I think one,

 9   for    a   public    health     standpoint    should   be

10   looking at the gradual reduction of the use as

11   alternates are picked up and I see a head-nod

12   on that.

13                  So, with that, I'm turning to the

14   manufacturer and see what the general plans

15   and thoughts are going forward between now and

16   end of the transition.

17                  MR.    CAMPBELL:    Well,     certainly,

18   we've agreed to change the labeling, which is

19   going into effect shortly.         That, I believe,

20   is going to have some effect on the demand and

21   we will mostly likely see that demand taper

22   over   time    and    we   will   reduce     production




                          Neal R. Gross & Co., Inc.
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 1   accordingly.

 2                   It is our hope that we would have

 3   a     replacement         product       available        before

 4   December 2011.       Again, that depends on how

 5   well we write the NDA and get it to you in a

 6   timely manner.       And in that event, we would

 7   transition out of the CFC into the HFA product

 8   before the sunset date for the CFC.

 9                   DR. CHOWDHURY: Just a bit more, I

10   mean, it is coming back repeatedly as having

11   an    alternate    HFA     product,      which,     if    it

12   happens, it happens.

13                 If     it    is    not    there,    and     you

14   mentioned you will make productions based on

15   the   demand,     one     question      is,   how    do    you

16   actually assess demand, when you do not know

17   what the purchases are in the first place?

18                 And     not    exactly      knowing     that,

19   knowing   the     end     date    from    the    public

20   standpoint,     it    would      make    more    sense     to

21   gradually, I guess, I'm repeating what Dr.

22   Parker just said.




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 1                 DR. PARKER: Wait a minute.

 2                 DR.      CHOWDHURY:     To       decrease

 3   production.    So, with that stated, I'm just

 4   wondering how you're going to plan for meeting

 5   the demand if you don't know the demand and

 6   where it's coming from.

 7                 MR. CAMPBELL: I'm giving personal

 8   opinion here, not company policy.       I'll start

 9   with that caveat, but as with albuterol, we

10   ceased shipment in early October 2008 so that

11   the pipeline would be drained by the end of

12   the year, and I would anticipate we would do

13   something similar to that.

14                 CHAIR SEYMOUR: Dr. Hendeles?

15                 DR. HENDELES: I just want to go

16   back to the message.      I don't disagree with

17   Dr. Liu, that it should be really targeted and

18   briefed for the consumer, but I think that

19   it's a teaching moment for other health care

20   professionals,      especially   pharmacists    and

21   people who work in pharmacies and drug stores,

22   and I think it's important to get to them the




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 1   essence of what my presentation was, is that

 2   the alternative tablets are not effective,

 3   that these patients may need steroids and they

 4   need to be under the care of a doctor and if

 5   they had persistent asthma, they need to be on

 6   an inhaled steroid.

 7                  I   think   that   would    be    a   great

 8   teaching moment to get across.        There are

 9   things   you    can   subscribe    to,    like    the

10   pharmacist letter, et cetera, that is kind of

11   like the medical letter, and a large number of

12   pharmacists would read that, if there were

13   those    recommendations      targeted      at   these

14   publications.

15                  CHAIR SEYMOUR: Dr. Parker?

16                  DR. PARKER: Yes, and I certainly

17   agree with that, having something that can be

18   over-arching, that could be used as part of a

19   teachable moment for everyone concerned with

20   health and taking care of people who have

21   respiratory,       lung,   airway,       inflammatory,

22   brochospastic, reactive conditions, whatever




                        Neal R. Gross & Co., Inc.
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 1   language we want to put on them or whatever

 2   they call them.

 3                  But let me just sort of nuts and

 4   bolts say, if I had a limited amount of money,

 5   you know, the pot was not endless, and my

 6   primary goal was to try inform the people who

 7   use the product, okay, that it's coming off

 8   the market and that they should be seeking

 9   primary     care   for   this    condition   through

10   someone who has expertise in it and that the

11   best   products     available     for   treating    this

12   condition    require     a   prescription,    I    would

13   design the campaign by beginning, by finding

14   out how much it costs and seeing if I could

15   get a hold of better information that tells me

16   where these things are being bought.

17                 I    actually     think   that's    worth

18   doing.    If there are certain places, certain

19   locations that account for 70 percent of the

20   purchase, that's a really good place to be

21   going with this and in lieu of all the options

22   that are out there in the world because they




                        Neal R. Gross & Co., Inc.
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 1   do go in a store and they do buy them and

 2   they're not coming from anywhere else.

 3                So if there was a way to target

 4   where those are geographically and even by

 5   types of stores or zip codes or whatever it

 6   is, if I could get a hold of that, I feel like

 7   that's   probably      a    cost   effective      way    to

 8   approach the campaign.

 9                Then the other thing really is,

10   before   going   any       further,   I   think    you've

11   gotten from this side, what's the content,

12   really spending the money, which won't be a

13   huge amount, to sit down and talk to users and

14   ask them these incredibly important questions,

15   where do you buy it?         Under what conditions?

16                It is coming off the market.               What

17   are the most important messages for you?                If

18   we're going to shake this, what can we put in

19   these, that is useful and actual?           It builds

20   the credibility of the FDA as a source of

21   trusted information.         It's a partnership and I

22   really think that it's not that expensive.




                      Neal R. Gross & Co., Inc.
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 1   It's just not that often done.

 2                   I certainly would be glad to put

 3   you in touch with people who could help even

 4   facilitate doing that and putting you in touch

 5   with    users    in     different    places around the

 6   country and you know, I think that that is

 7   money very well spent and you're not talking

 8   about an enormous amount.

 9                   So, I think the strategy of the

10   campaign really is to find out how to target

11   it and to really partner with the people that

12   we're   trying     to    reach,     and   then   having   a

13   couple of over-arching things for those who

14   are in the practice of pharmacy and clinical

15   medicine and ER medicine, so that we're aware

16   and we do our job on that end as well.

17                   CHAIR SEYMOUR: Dr. Reidenberg?

18                   DR. REIDENBERG: Yes, I think this

19   sort of a discussion of users ought to also

20   include an assessment of whether these people

21   have persistent asthma or simply intermittent

22   asthma.




                           Neal R. Gross & Co., Inc.
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 1                 All of our discussion has assumed

 2   that these people are persistent, patients

 3   with the persistent asthma, who are using this

 4   with self-treatment and therefore, not getting

 5   care and not getting steroids.

 6                 This is an assumption.          We don't

 7   have any data on this.          The little bit that I

 8   could find and presented was the opposite.

 9                 And    so,   I     think    that   if     we're

10   going   to   do   these    focus    groups,      this    is

11   important because when the good propellant

12   inhalant comes along and it's proposed for

13   over-the-counter use, I can see these same

14   arguments occurring again and in the absence

15   of   data,   we   won't    be    better    off    to    know

16   whether they're valid or invalid.

17                 CHAIR SEYMOUR: Thank you.           I think

18   we probably should touch on the evaluation

19   question, which is the last question, and we

20   wanted to get some input on how we can assess

21   our educational campaign and if we've achieved

22   our goals and reached our audience and if




                         Neal R. Gross & Co., Inc.
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 1   there's any need to modify a plan.

 2                We'd like to see if there's any

 3   comments about that, and I think this is a

 4   little bit unique, because we do have sort of

 5   a limited time line we're looking at for this

 6   campaign.   So, we'd appreciate any comments.

 7   Dr. Reidenberg?

 8                DR. REIDENBERG: Well, it seems to

 9   me, the goal is whether the people know that

10   it won't be available, before they find an

11   empty shelf, and that would be the goal. The

12   purpose is, they should know.

13               I    suspect   that   we   can't   assume

14   these people are all dumb-bells, that if they

15   were told it wasn't available, wouldn't know

16   what to do or what to ask or who to ask.        They

17   probably can do this.

18               And so, if we look at this, the

19   primary goal is, they should know that on a

20   certain date, it won't be available.       Do they

21   find this out?

22               CHAIR SEYMOUR: Dr. Schmidt?




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 1                  DR.     SCHMIDT:    I    guess    to   some

 2   extent, if you see the tapering, you figure

 3   they probably found it out.            If you don't see

 4   the tapering, I don't see how they can miss

 5   it, if you're labeling, I thought, you know,

 6   that by December 2011, that they all come to

 7   the store and they're in panic-mode because

 8   the shelf is empty.

 9                  But it seems that the evaluation,

10   I mean, if there are two messages, those are

11   the two, kind of areas of evaluation.             One is,

12   as we just heard, in terms of, you know, do

13   they know that it's going to come off the

14   shelf and do they know what to do about it?

15                  I don't know if we can get at the

16   second, which is trying to get them into some

17   kind    of   medical    home,     where   they    can   be

18   followed for their asthma.          I don't know how

19   you can measure that.       You know, if they move

20   from buying Primatene Mist, to going to their

21   doctors, I just can't see how you could get at

22   that.




                          Neal R. Gross & Co., Inc.
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 1                  CHAIR       SEYMOUR:       So,         you're

 2   suggesting at least the one objective data

 3   would be the sales data. Dr. Reidenberg?

 4                  DR. REIDENBERG: Yes, there is an

 5   alternative.         We're    assuming    these       people

 6   don't have a medical home.          It's hard for me

 7   to   picture    college      students    don't    have     a

 8   family that have a physician contact.

 9                  Student health service has it, so,

10   they do have a medical home.

11                  Secondly,      and     I've      had     this

12   experience with the COX-2 inhibitors, that

13   certain patients, for various reasons, despite

14   the risks, felt these were the best medicines

15   for them and boy they hoarded, when they knew

16   it was coming off.

17                  So,    I   can't   predict    what      these

18   people with intermittent asthma will do, when

19   they know it's coming off, so I wouldn't know

20   how to interpret sales figures.          It could go

21   either way, and to repeat, if the primary

22   message is, do they know it's coming off, then




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 1   the efficacy is, have they learned it's coming

 2   off?

 3                   DR. SCHMIDT: But who do you ask

 4   that?

 5                   DR. REIDENBERG: I don't know how

 6   you get these focus groups of users, but the

 7   people that I would ask would be later on, the

 8   people who are buying them.           They're the ones

 9   that    have    to    know,   it's    not   going   to   be

10   available in the future.

11                   How you assemble such a group and

12   do   it,   is    social    science,    rather   than

13   pharmacology.        So, I'll back off there.

14                   DR. LEONARD-SEGAL: Yes, I'd like

15   to actually ask a question about that, because

16   if we follow the one year suggested time line,

17   I don't know how we have time to evaluate what

18   we've done and so, I guess that I would like

19   to pose a question.

20                   How essential is it, that we do

21   evaluate the impact of what we're doing, or

22   should we just do it and hope that it works?




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 1                   CHAIR     SEYMOUR:        Dr.    Liu?        Dr.

 2   Hendeles?

 3                   DR. HENDELES: I don't think it's

 4   going to serve any useful purpose, but it

 5   would be interesting to see what kind of anger

 6   is    thrown    at    the    FDA    and     to    document        or

 7   measure that, and if there isn't much, than

 8   you know you've done an effective job.

 9                   DR.      LEONARD-SEGAL:           Does       the

10   absence   of     expressing        anger    mean there is

11   none?

12                   DR. LIU: Sure.

13                   DR.    HENDELES:      I    just       wonder   if

14   there's any lessons that Diana can share with

15   us,   that     they've      learned    from       trying     to

16   disseminate the NAEPP guidelines.

17                   DR.    SCHMIDT:      Yes,       we've    learned

18   lots of lessons.        We've taken a new approach

19   to our 2007 guidelines as a result of that.

20                   But again, and it's more with the

21   implementation,        you    know,    we       can    get   the

22   guidelines polished and ready to share with




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 1   clinicians but you know, again and again, we

 2   hear that they haven't uptaken the guidelines

 3   to the extent we'd like them to.

 4                    So,     we've    tried     to   get    the

 5   implementers more involved this time to look

 6   at   what    did    we     do    wrong?       What     are    the

 7   barriers?     How do we get through that this

 8   time around?

 9                    So, we're taking a whole different

10   approach    in     how    to     assemble    the     group     of

11   people that do implement, but again, we know

12   who those are.         We know the target group.             We

13   can get that input, and that's what we keep

14   hearing, you know, we need the input of the

15   people buying the Primatene Mist and it's just

16   amorphous.    We're not quite sure.

17                 So, we have the advantage that we

18   know who the users were and we've been able to

19   get their input, in terms of a different way

20   of disseminating information this time around.

21                 DR. LEONARD-SEGAL: Can I just ask

22   one more question here?            In terms of your




                            Neal R. Gross & Co., Inc.
                                   202-234-4433
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 1   organization, Mothers, you had done the survey

 2   and you had something like, I don't know, 92

 3   percent of people didn't use these products,

 4   so eight percent did.

 5               Do you know who those people were

 6   who answered your survey and is there a way

 7   for you to help us find out who is using?

 8               MS. SANDER: We actually tried to

 9   pull that information on the online survey,

10   just a few moments and we will try and do

11   that.

12              You know, but one thing that I

13   would like to add is, there will be anger and

14   it will be directed at who ever is delivering

15   the message and part of what we encourage you

16   to do is focus less on the ozone and focus

17   more on, you know, the better care and if, at

18   all possible and if it's something that we

19   need to ask Congress for, vouchers, so that

20   they can get that care, just like there were

21   vouchers for the television transition.

22              You know, those vouchers can be




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                           202-234-4433
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 1   used at public health departments, so that

 2   we're making sure that they're going to the

 3   right people.

 4                DR. SCHMIDT: It seems like in the

 5   presentations, I don't know, did I hear this

 6   right, that an emergency albuterol inhaler was

 7   given to a person, if they came into the

 8   pharmacy and they were no longer available?

 9                DR. LEONARD-SEGAL: That was Ruth

10   Parker.   I think she found one pharmacy that

11   did that, among a group and I think she didn't

12   know how they were authorized to do it.        Other

13   pharmacies said that they didn't do it.

14                DR. SCHMIDT: Okay.

15                DR. LEONARD-SEGAL: One said that

16   they would ask a supervisor if they could do

17   it.   So, that was an anecdotal thing.

18                DR.    SCHMIDT:   The   only   image   if

19   have that could be troubling is if somebody

20   has missed the message, you know, on December

21   2011 and they go to the pharmacy in distress,

22   looking for relief and there's nothing on the




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 1   shelf.

 2                  I don't know if that's possible it

 3   would happen, but would there be some kind of

 4   contingency,     maybe    the     voucher   idea     or

 5   something?

 6                  DR. REIDENBERG: Emergency room.

 7                  DR. SCHMIDT: Emergency room, okay,

 8   yes.

 9                  DR.     REIDENBERG:      That's       what

10   they're saying.       They should get medical care.

11                  MS. SANDER: The number of people

12   that   are    suddenly    gasping    for breath, you

13   know, they're wheezing, they're choking, they

14   feel   like    they're    going    to   die,   are    not

15   rushing to the pharmacy, where they can stand

16   in line and pay for a product, you know,

17   that's just not happening.

18                  I've lost my inhaler before.          I've

19   lost it while traveling in another country.               I

20   called my doctor.       I had a new inhaler within

21   an hour and a half.       I wasn't having any

22   symptoms, but you don't leave home without it.




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 1                 It's    more    important         than   your

 2   American Express card.

 3                 DR. HENDELES: But you know, if you

 4   go to a CVS, a Walgreen's or a Wal-Mart or a

 5   Target, all their pharmacies are connected by

 6   satellite and if you have a prescription on

 7   file at any CVS in the country, you can get a

 8   refill of it in Arizona, or where ever.

 9                 So, I guess that's an advantage of

10   using that type of pharmacy.

11                 CHAIR    SEYMOUR:      So,    I    think   we

12   probably    have    covered    all    the    different

13   topics.    I just want to ask the FDA members of

14   the panel, because we've obtained a lot of

15   feedback from our other panel members and some

16   audience members as well.

17                 If we have any further questions

18   that we want comment on from the panel, or do

19   we feel like we have all the feedback that we

20   need at this time, to move forward?

21                 I'm     not     seeing       any     further

22   questions.     So, I want to thank everyone for




                         Neal R. Gross & Co., Inc.
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 1   attending our workshop today and I want to

 2   especially thank our panel members and our

 3   speakers.    I think it was a good discussion

 4   and   we   at    the   FDA   will   take   this   under

 5   consideration, as we move forward with the

 6   educational campaign.        Thank you.

 7                   (Whereupon,     the    above-entitled

 8   matter went off the record at 3:19 p.m.)

 9

10

11

12

13

14

15

16

17

18

19

20

21

22




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          A             108:21 137:1,3        75:7 127:8 186:20    24:11 25:16 26:5    advisors 207:13
AAFA 215:9              143:7 146:11        actively 115:6         54:11 217:19        advisory 22:15
abilities 139:1         148:2 161:2,16      activities 31:17      adequately 23:22       28:9 104:20 105:1
  147:8 164:14,16       162:6 164:19          197:4 214:5          241:10                110:19 111:12
ability 137:13          185:10 194:8,9      activity 32:8 48:6    adherence 265:2        241:17
  139:12 158:20         229:7,9 241:8         113:13               300:19              advocacy 77:16
  164:3 218:1 265:3     242:12 257:21       actual 60:3 67:19     adhering 266:12        206:10
able 7:4 59:19 79:4     258:9 295:12          67:21 76:17 77:17   Adjourn 3:13         advocates 206:8
  81:15 93:4 99:5     accessible 221:14       81:15 86:14 94:5    adjusts 281:12         218:21
  105:21 122:3        accessing 212:13        132:11 138:3        administer 49:16     advocating 246:13
  124:5,19 131:1      accommodate             145:17 158:17        68:2                aerosol 1:6 11:10
  136:22 141:5,10       118:8                 163:11 164:15       administration 1:2     24:21 28:7,15,21
  152:21 154:14       accomplish 62:1         199:5 245:3          40:8 207:5 209:10     29:14 32:12 47:22
  158:1 162:22        account 309:19          310:19               214:15                222:7
  168:13 173:7        accurate 159:14       actuated 126:12       admit 262:13         aerosols 19:17 20:8
  182:4 200:4           263:4 271:4           130:8               admitted 44:19         23:10
  209:17 224:17       ache 100:16           actuating 127:13       50:5 56:4 235:22    Affairs 2:5 5:10
  241:7 242:6,14      aches 100:16          acute 34:11,21 35:2   admitting 44:7         166:3,7
  247:18 264:13       achieve 14:8 305:5      47:7 49:10 50:11    adolescents 259:17   afford 136:22
  273:8 276:20        achieved 32:9           51:17 61:20 63:11   adopted 55:3           188:15 199:11
  281:20 318:18         312:21                91:4 190:9 227:17   adrenal 93:8           202:7 229:6
above-entitled        achieving 116:16      ad 42:20 170:8        adrenergic 7:12      affordable 221:13
  112:9 192:13        act 8:6 11:17 14:22     171:22 172:4,21      48:6,9 85:10        afraid 264:15
  323:7                 16:7 17:17,18       adage 35:3            ads 170:17 172:18    afternoon 6:1 8:12
absence 312:14          29:16,20 96:7       add 53:13 61:18        172:19 176:21         85:21 192:3,18
  317:10                103:4 105:6           69:12,19 74:5        178:4 202:1           206:2 224:16
absent 83:20            138:14 139:2          90:5 93:14 224:13    267:11,18           age 78:9,11,11,13
absolute 79:18          141:14 196:6          257:17 267:21       adults 85:6 139:18     134:5,13 135:2
  186:16                212:7 261:5           285:7 319:13         154:19 155:1          155:7 259:15
Absolutely 125:18     acting 7:12 33:1      added 159:16          Advair 64:7          agencies 213:14,18
  201:9 238:20          36:20 37:17,18      addicted 156:1        advance 33:22        agency 2:13 11:4
  266:14                39:4,16,20 40:8     adding 40:4 252:17     232:21 233:21         27:16 99:10 101:9
absorption 49:3         40:12,15 46:16,20   addition 50:15,20     advantage 121:4        104:13 117:4
  116:18                46:22 50:12,16        51:10 56:11 69:8     268:6 318:17          207:10 211:16
abstract 89:22          51:18 52:7 54:3       102:16 188:19        322:9                 239:22 284:3
abuse 70:3,5            61:17 90:4 108:16     255:15              advantages 107:5     agency's 104:9
  107:15,18,19,21       113:14 207:19       additional 6:3        adverse 109:20       agenda 9:4 112:13
  156:6                 274:9                 74:21 92:17 109:8    239:18 279:2          135:11
academic 89:13        action 34:17 47:5       135:8 180:7         advertise 123:3      agent 120:16
Academy 111:9           196:3 201:8           210:21 291:6        advertised 134:18    agents 269:17
acceptable 19:1         213:10 217:16       address 34:2          advertisement        ago 19:10 23:14
  213:1               actionable 159:6        126:11 183:10        289:7                 35:4 41:8 52:19
acceptance 129:22       226:21 253:9          267:1               advertising 115:7      75:12 84:4 106:22
accepted 130:3          259:5,8 260:1       addressed 286:7       advice 242:16,16       128:6 150:6,20
access 49:18 52:6       295:2               addressing 33:21       271:13                197:6 202:10
  54:7 65:4 71:12     activated 38:13         161:5               advise 162:9 297:4     249:8 278:19
  77:16,21 82:17      active 26:11 27:16    adequate 23:19,20     advisor 11:1           282:20 287:3


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agonist 36:20 37:17     24:16,19 26:16      alpha 48:6,9           amounts 70:6          153:15 156:21
  37:19 39:17,20        33:2 34:10 40:13      113:12               Amphastar 2:12        183:3,4 234:22
  40:9,16 43:13         41:18 42:9 44:14    alter 117:4             9:15 112:21          237:8 241:22
  50:20,21 51:12        45:11 46:8 47:10    alterations 55:3       amphetamine 58:1      242:1 265:6
  52:7,9,16 53:8,19     49:1,20 51:13       alternate 23:19,20     anaphylaxis 125:9     268:12 282:3
  54:3 55:13 57:20      52:22 53:3 56:3       24:10 31:22 32:20    Andrea 2:6 5:6,18     304:13
  59:1 60:10 74:19      60:11 63:7 71:9       120:8 121:12          260:9               anymore 24:4 31:4
  85:10 90:4 108:15     73:16,22 90:22        129:12 228:5         Andrea's 304:1        65:21 89:16
  108:16 113:12,12      91:14 92:3 96:3       275:11,19 276:3,7    and/or 114:22         118:17 190:20
  123:15 128:2          96:20 98:4 102:7      306:11               anecdotal 320:17      245:6 302:18
  265:17 273:5,18       102:15 103:8        alternates 26:11       anesthetics 48:7     anyplace 69:14
agonists 46:17,18       111:17 119:16,16      305:11               Angeles 133:16       anyway 76:2 89:15
  49:7 50:12 51:19      123:7,16 127:19     alternative 40:11      anger 317:5,10        149:14 152:3,17
  55:19 107:15          128:4,8 156:9         44:3 57:11 85:8       319:13               154:1 191:21
  274:9                 166:20 177:11         89:18 92:4 102:13    angry 287:16,18,22    234:5 276:22
agree 77:3 90:6         178:11 179:6          115:18 117:9,16       288:1,1              277:1
  97:6 136:8 142:12     180:4 183:18,22       200:6 257:13         announcement         Anyways 45:21
  143:14 145:11         184:7,12,16,18        271:7 284:20          170:8 292:18        apart 39:18
  232:19 237:22         185:2,13 201:15       300:4 303:20         announcements        API 116:16,17
  259:6,18 308:17       203:1 223:6 228:7     308:2 315:5           182:1 289:3         apparent 253:15
agreed 305:18           228:12,17 229:4     alternatives 3:5 9:9   announcing 245:13    apparently 41:18
agreeing 267:5          255:1,2 260:16        18:22 64:20 88:12    annual 86:10          63:1 85:2 114:15
agreement 109:13        269:12 278:2          95:4 180:12 199:8    answer 58:10 62:10    140:20 273:22
  143:1,16 158:17       279:10,15 288:14      222:16 225:20         84:13 94:5 99:14    appear 271:8
ahead 4:4 10:19         297:2 302:5 307:9     268:13,14 284:22      193:19 198:20       appears 131:11,13
  17:22 112:3           320:6                 295:9 303:18          204:21 212:8        applaud 33:20
  129:12 135:7        alcohol 122:3         altitude 12:8           228:22 247:18        197:9 207:5,6
  207:9 238:21        alert 9:2             altitudes 12:3          248:16,19 249:3     application 74:8
  305:5               algorithm 142:4       aluminum 121:21         265:5 268:22         260:20
aim 13:14 16:19       align 137:7,12          126:2,3               283:10,13           apply 184:8
  19:5 31:21 33:3,5     139:11 147:9        amazing 69:4 115:5     answered 180:2       applying 265:2
air 8:6 11:17 14:22     164:14                265:14                247:8 319:6         appointment
  15:19 16:7 17:16    aligned 139:13        ambulatory 51:3        answers 10:9          140:10
  17:18 29:16,19      alike 233:7           America 1:1 77:12       170:16 192:3,11     appreciate 127:22
  38:11,17,18 125:7   allergies 193:10        137:11 205:22         200:1 289:6          128:13 130:20
  200:9,11 261:5        213:19 215:14       American 111:9         Antarctic 13:2        131:19 135:22
  298:15              allergists 42:13        146:2 219:7,8        anti 82:6             242:2 269:20
airway 38:15 43:10    allergy 2:2,3 4:15      263:10 297:16        anticipate 117:22     313:6
  43:11 51:1,9          5:5 111:9 192:21      322:2                 307:12              appreciative
  58:21 70:18           193:4 205:21        Americans 77:6         antihistamine         183:20
  233:19 270:21         206:3 286:22          224:7                 88:17 189:20        approach 137:5,18
  308:21              allocate 221:4        American's 139:18      antihistamines        139:4 145:15
airways 49:5 61:21    allowed 21:9 46:2     amorphous 318:16        88:14 95:5           184:2,7,11 206:19
  256:16                72:12,20,20 73:2    amount 21:8 25:21      antiquated 264:1,2    206:20 233:9
albeit 278:19           73:4 97:18            55:5 122:2 309:4     anti-inflammatory     258:18 270:10
albuterol 23:9,10     allows 26:9 58:5        310:13 311:8          80:5 97:3            296:4 299:15
  23:12,18 24:3,8       142:7               amounted 76:3          anybody 152:19        310:8 317:18


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  318:10                178:11 289:4        49:10 50:11 51:17     293:20 298:10,11      103:18 111:1
appropriate 70:7      ASAP 299:11 301:3     52:20 53:9,21         308:5 311:21,22     authorized 320:12
  85:3 107:16         asked 51:17 109:5     55:18 56:19 57:2      312:3 314:18        authors 85:1
  111:22 176:6,20       217:3 249:8         57:8 58:21 60:18      315:18              autopsy 41:14
  202:15 203:3        askew 280:1           61:6,8,9,16,20      asthmatic 71:6        availability 6:14
  208:20 235:14,19    asking 154:17         62:2,5 65:12          75:16 272:21          8:7 23:19 214:6
  239:17 269:17         155:11 194:10,19    69:14 75:19 78:5    asthmatics 84:21      available 6:19
  271:5,6 274:1         236:8 286:14        78:9,13,16 79:13      85:19 90:9 192:22     18:20 32:18 34:16
  282:12 283:8        aspect 176:5          79:16,22 80:4,13      193:5 287:1           34:16 48:1 57:13
appropriately         aspects 18:20         81:5 82:5,6,10      astounding 51:20        63:22 65:10 88:22
  273:11 274:10       asphyxiation 42:7     84:18 85:3,6        asymptomatic 36:1       91:3 102:7,16
approval 110:20         42:10               86:19,22 88:1,18      83:18                 106:5,8 108:10
  111:6               aspirin 99:19 100:7   88:19 89:9 90:1     athletic 300:11         113:3 114:9,13,13
approved 113:10         171:20              91:5,8 92:1,11      Atlanta 143:5           114:15 115:13,21
  118:5 253:6         assemble 316:11       95:8 98:20 109:2      149:11,16 156:20      117:3,7 119:12
approximately           318:10              110:10 111:4,19     atmosphere 11:20        122:1,12 124:8
  16:2,16 21:18       assess 285:20         113:11 133:22         12:3 25:22            141:12 147:3
  24:7 28:17 113:22     306:16 312:20       138:18 147:22       attach 178:17           150:9 153:7 155:1
April 26:22           assessed 237:15       152:2 153:19        attack 37:1 38:20       160:2 162:11
area 12:14 13:1,3     assessment 311:20     154:6,12 156:14       44:9 45:8 47:2,7      184:3 190:16,20
  75:7 81:21 133:14   assign 270:20         159:20 160:4          61:6                  191:21 196:18
areas 101:15          assigned 50:14        161:10 162:1        attacks 36:5 91:4       199:9 209:1 211:1
  132:14 186:21       associated 111:4      191:13 192:21       attendees 219:10        211:6,19 213:4
  187:3 244:6,6       association 206:4     193:4,8,10 194:5    attending 323:1         225:19 226:13
  245:1,2 292:3,4       215:9 219:8,8       196:3,6 200:20      attention 62:9          229:10 240:4
  314:11                242:10 297:15,17    201:8,9 204:7,15      92:12 252:20          241:2 245:15
argue 45:14 56:6        297:22              205:21 206:3          292:17,19             249:3 250:13,22
  231:2 252:12        associations 218:6    207:19,21 208:10    attitude 138:12         251:19 256:9
argued 46:15            219:5,6 301:15      208:16,17 213:19    attractive 128:16       260:1 268:19
arguments 312:14      assume 313:13         214:7,9 215:1,4       129:19                271:14 276:14
Arizona 322:8         assumed 312:1         215:14 216:19       audience 72:17          281:13 284:12,21
Arkansas 114:14       assuming 272:4        217:12 218:19         167:4 168:1,2,8       294:19 302:17
Armstrong 112:15        315:5               221:16 225:21         169:4,14 174:20       306:3 309:11
  112:20 114:10       assumption 312:6      234:19 235:20         179:10,12,19          313:10,15,20
  115:10 119:13       assumptions           236:2 237:8 239:3     180:14,15,18          316:10 320:8
  122:15 275:17         210:16              243:20 245:11         181:2 184:14        average 44:21 45:2
Armstrong's           asthma 3:5 6:22       256:14 257:3,7        221:21 238:6          139:20 140:2
  117:11                7:18,19,22 9:8      259:9,16,20 263:7     242:4,21,22 243:3     200:22 282:17
Army 186:13 187:8       20:8 34:1,3,13,18   263:9 264:18          243:6,14,22           283:1
array 170:3 265:14      35:5,6,15,16,18     267:9 268:3,19        244:21 285:9        avoid 69:6
arrest 47:20            35:21 36:8,10,15    269:17 272:8,12       286:17 293:13       avoiding 116:2
arrive 278:3            36:16,17,22,22      272:21 273:6          312:22 322:16       aware 11:19 87:11
art 145:4               37:4,5,6,14,20      274:17 276:16       audiences 170:12        125:7 159:15
arthritis 100:10,16     38:2,7,9,18 39:6    277:3,6,15,20       audio 177:16            191:11,14 274:3,8
article 15:12           39:15 40:21 41:6    278:9,19,20 280:8     181:12 204:5          311:15
articles 41:12          41:10 42:5 43:8     281:3 282:3           289:2,8             awful 76:20 267:7
  170:13 177:5,7,17     43:10 44:7,9 45:8   284:17,21 287:1     Australia 42:5        axis 21:13


                                 Neal R. Gross & Co., Inc.
                                        202-234-4433
                                                                                            Page 327

a.m 1:10 4:2 10:3   84:12,15,15 87:18   behaving 127:7,9        273:5,18 274:9      bits 159:6
  112:7,10,11       92:15 94:7 97:13    behavior 52:8         better 40:2 59:9      bit-size 229:20
                    102:2 126:4,10       218:16                 81:9,14 88:1,5      black 231:7
         B          149:1 189:4         behold 150:21           91:2,2,7,11 92:1    blah 231:5,5
back 13:8 15:6,13  barriers 65:4         151:3                  93:2,6 94:10 98:4   blamed 42:2
 21:11 29:15 41:3   123:18 143:8        belief 47:15            102:16 106:16       blaming 41:12
 53:17 54:8 60:11   146:12 148:3        beliefs 42:11           108:22 116:14       blasts 289:7
 67:5 68:19 69:2    188:18 318:7        believe 107:2           139:8 146:21        blind 58:7 60:1,17
 84:1 88:7 100:16 based 37:10 38:3       115:17 202:22          164:2,6 165:5       blitz 291:20
 107:3 110:5 112:7  39:19 113:19         221:18 224:19          175:12 179:12       block 241:21
 155:19 157:7       133:12 138:5         305:19                 206:19 210:12       blogosphere 216:5
 158:13 163:6       140:15,19 143:2,3   believed 43:3           232:14 278:14       blood 2:11 48:15
 169:16 170:20      144:13 146:13       benefit 25:20 28:1      281:16 282:1          49:2
 173:7 190:3        149:5 157:16         29:5 35:13 55:6        283:6 301:17        blue 13:1 21:6,9,17
 194:17 195:1       166:10 167:5         64:9 92:9 230:12       309:15 312:15         196:5,5,8
 223:11 238:5       179:12 184:11       benefits 279:14         319:17              board 223:9 261:11
 239:19 249:10      186:19 193:6        best 7:7 8:18 32:19   beyond 17:10          boarded 160:16
 264:9 266:7 270:6  212:19 249:18        65:5,9 81:1,10,17      212:13 217:15       body 17:2 110:21
 275:10,11,16       258:12 287:21        90:2,6 93:14,21        235:6 262:2         Boehringer 223:19
 279:2,16 283:19    296:4 301:1          97:6,9,11,17           292:16 294:12         239:17
 285:18 291:8       306:14               99:12,14 104:21        302:16              bolts 309:4
 301:3 306:10      basic 139:19,19       134:11 139:16        biases 147:18         book 89:2,6 204:17
 307:16 316:13      140:6,12 264:19      141:12 143:10        big 21:21 50:22       books 204:10
background 11:8    basically 28:13       145:19 161:15,17       136:20 147:11       borders 157:19
 11:13 101:4        34:20 88:4 89:22     161:22 162:2,4,5       156:22 214:2        Boston 50:7,13
 135:18 146:6,22    119:17 234:14        163:12 165:1           275:8 276:17        bottle 93:10 121:21
 281:6              265:6                168:10 175:6           277:4 291:20        bottom 61:2 146:4
bacterial 151:12   basis 214:17          179:22 180:20          297:9                 151:4,22 159:11
bad 12:15 87:2      218:17 227:14        191:20 208:19        bigger 133:15           161:22 237:18
 136:20 149:12      235:3                210:5 221:15           161:2                 246:15,16 247:12
 152:13 225:21     Bayview 282:19        226:13,19 244:22     biggest 111:11          252:1,3,4
 255:13            bear 110:12 117:6     258:6,13,18 259:6    billion 113:22        bought 64:17 153:5
Badrul 2:3 5:3     beautiful 75:5        260:4 270:9,10       bio 47:22               180:4 250:18
 110:17 197:3      beautifully 98:22     276:14 296:13        bio-availability        309:16
Badrul's 283:17    beauty 182:17         309:11 315:14          125:4               box 118:6 231:7
ban 16:6,10 30:5    218:13              beta 36:20 37:17,18   bio-available 48:2      245:5,10,20
banned 19:8,10,11 beclomethasone         39:16,20 40:9,16       48:21 73:17           251:22 252:1,21
 19:15 20:1         26:18                43:12 46:16,18       bit 5:19 28:4 30:15   boy 315:15
banner 172:18,19   becoming 211:6        49:7 50:12,20,21       30:16 48:19 62:15   brain 204:11,12
 172:21             302:3                51:12,18 52:7,9        80:18,19,21         brain-storm 181:1
banners 170:19     bed 47:4              52:16 53:8,19          118:16 136:2        brand 57:14 213:2
 289:3,8           began 41:5            54:3 55:12,19          149:22 179:7        branded 88:15
bar 254:3          beginning 304:10      57:20 58:22 60:9       210:2 226:3 238:2   brands 64:9
barber 218:13       309:13               74:19 90:4 107:15      238:7 250:9         break 9:13,14
barn 200:3         begun 181:5           108:14,16 113:12       288:22 306:9          106:21 112:4,8
barrier 25:17      behalf 66:17 205:2    113:14 123:15          312:7 313:4           225:17
 27:21 29:3 75:22   206:3 222:6          128:2 265:16         bitolterol 26:19      breath 7:17 35:1


                              Neal R. Gross & Co., Inc.
                                     202-234-4433
                                                                                             Page 328

 40:19 126:11         7:13 33:1 34:6,8    burning 248:9        campaign 115:7        capability 121:3
 134:20 153:20,22     34:12 39:4 40:22    buses 170:18           134:10 168:11,20    card 141:8 191:13
 157:11 190:13        41:7,17 45:9,19     business 187:20        169:1 170:6           210:14 322:2
 209:17 270:12        50:16 51:6,8          230:12,21            171:21 172:1        cardiac 42:9 47:19
 272:5 277:8          57:18 61:13,16,17   busy 263:13            174:15 179:17         100:11
 321:12               69:20 70:14,18      buy 54:22 101:5        191:6 214:2         care 35:14 42:12
breathe 232:14        73:19 84:17 85:4      115:22 143:22        220:21 221:10,12      47:15 53:12 68:5
 252:6 261:19         85:12 98:19           152:18 153:13        225:12 226:6,8,22     69:15 80:12,13,15
breathing 7:19        196:17 198:5,7,10     156:5 175:9 188:3    227:1,8,10 228:9      80:22 81:9,18
 159:21 160:4         198:17 204:21,22      188:15 227:15        266:12 271:11         82:18,20 83:3,17
 252:7                268:1 281:12          230:18 272:15        300:18 304:3          97:7 99:8 102:10
breath-activated      282:1,14,21           304:13 310:1,15      309:13 310:8          103:15 104:6
 124:17              bronchodilators      buying 63:15           311:10 312:21         106:17 113:19
breath-actuated       38:19 61:12 85:9      132:15 147:5         313:6 323:6           136:12,13 137:1
 68:17 124:14         128:3 196:12,22       150:18 152:6       campaigns 168:6         137:10 138:18
 128:16,19,22         197:13,16 202:16      236:18 245:6         171:8,11 182:15       141:3 143:10
 129:4                275:13                246:8 249:13         186:10 221:8          148:2 149:2
Brennan 2:13 11:2    bronchodilitation      291:1 292:13       Campbell 2:12           151:17 160:5,7
 11:3 183:15,15       269:15                293:7 294:4          9:14 112:14,18        161:8,20 185:6,9
brief 107:1          bronchospasm           314:20 316:8         118:4,11 119:3        190:9 191:5 194:9
briefed 307:18        267:18 270:11         318:15               120:17 121:10,14      204:18 205:1,3
briefing 85:17        278:4               buys 134:6             123:2,20 124:15       207:18,21,22
briefly 14:13        bronchospastic                              125:10,14,18          208:8,18,18 209:5
 110:15 222:5         61:10 143:11                  C            126:1 131:11,16       211:10,10 214:20
bring 6:3 43:15       149:3 233:18        C 162:5                239:15 240:12,20      214:20,21 216:12
 54:8 72:9 135:9      256:15 258:12,19    CAA 14:21              244:8 247:14          221:13 225:22
 266:7 278:10         270:20              calculate 141:5        248:1,4,8,12,21       226:19 227:16,17
 283:19              Bronkaid 250:4,12    calculation 118:18     249:18 250:6,11       230:1,2 231:19
broad 167:3 168:3    brought 11:11        California 15:8        250:16 251:2,7,12     234:1,20 235:6,19
 170:3 174:19,20      41:19 120:8           114:19               254:1,10,13,20        237:12 243:8,13
 176:5 177:5 238:3    163:17 226:4        call 18:6 25:1 40:18   255:12,18 291:4       243:16 256:11
 274:7                289:19                49:18,22 78:22       305:17 307:7          257:10,15 258:7
broadly 123:3        brush 274:8            140:8 144:9        Campbell's 179:13       258:11,13,16
brochodilator        budget 221:5           151:17 157:7         260:13                259:6,20,22 260:4
 280:21              build 230:11           173:22 202:16      Canada 21:4 52:19       263:9,19 266:21
brochospastic        builds 310:19          245:18 246:11,21     56:18                 270:10 282:9
 280:9 308:22        built 192:6            247:19 279:16      cancer 140:14           284:14 293:21
brochure 171:22      bullet 13:20 23:16     289:21 309:2       cancers 13:20           296:3 299:2
brochures 170:14      25:14 27:21         called 18:6 48:12    canister 63:2,19,20     307:19 308:4,20
 172:12,13,16         202:13 257:9          58:1 100:1 111:1     65:8 66:22 121:22     309:9 312:5
 289:5                268:3 286:7           171:12 172:5         125:22 126:2          319:17,20 321:10
bromide 17:11        bulletins 288:8        200:11 204:17        127:5 197:2 283:3   career 58:17
bronchial 7:18,20    bunch 147:6            321:20               294:10              careful 196:15
 113:11              bungalow 59:19       calling 67:1         canisters 53:8,16       255:7 303:9
bronchodilating      bungalows 59:18      calls 149:14,17        55:19 56:2,20       carry 195:16,22
 230:9               burden 214:9           155:12 178:4         74:16 85:14         carry-back 46:17
bronchodilator       bureaus 213:18         182:6              cap 265:13            carton 117:6


                                Neal R. Gross & Co., Inc.
                                       202-234-4433
                                                                                                Page 329

case 13:7 36:17       certainly 61:5        chains 65:2           challenging 32:6      Chicago 133:15
  126:1 192:7           81:14 90:8 92:18    Chair 1:11 4:3 5:16     127:15 211:11       child 49:19 71:6
  212:10 230:12         97:2 99:9 105:8       10:15 33:9 62:12      234:2 276:1           83:1,18,21 275:5
  300:11                105:12 113:7          74:20 94:17 95:19   chamber 71:14,17      children 59:16
cases 90:5              118:12 134:16         102:19,22 106:19    chambers 69:7,8         77:10,12 78:4,8
cashiers 245:22         147:12 164:4          112:1,12 117:20       71:12 127:13          78:15,17 79:12,20
  246:5                 187:22 191:11         118:14 119:7        chance 263:20           80:3,12 81:4 82:4
cataract 13:22          207:14 229:19         122:9 123:10          268:17                82:8 154:20 155:2
catch 252:19            248:22 278:17         124:11 130:19       change 6:13 30:20       155:7 188:17
catchment 81:21         281:1 286:22          135:6 165:18          119:11 184:11         191:9 214:2,7,10
catechol-O-meth...      292:4 298:19          183:13 185:19         204:14 243:17,19      214:10,22 243:8
  48:12                 305:17 308:16         187:19 189:7,11       261:3,4 287:17,21     259:14,17 273:12
categories 53:22        311:2                 189:22 191:22         305:18                273:16 275:8
  54:4 211:14         cetera 308:10           192:16 205:19       changes 9:2 13:22     children's 214:3
category 103:3        CFC 6:14 8:14 9:15      221:17 223:15         118:5 123:22          218:19
  104:10 105:5          16:3 20:5,17 25:2     224:14,22 226:1       127:11 200:13       CHIP 214:4,6
  278:22,22             26:1,21 28:14         228:21 230:5          287:20              chlorine 15:10
caused 51:9             29:14 32:11 44:16     234:7 236:5 237:4   changing 99:7         chlorofluorocarb...
causes 13:13 38:19      109:10,14 115:12      238:1,20 239:8        203:21                6:14
  82:16                 117:1 121:16          240:1 242:3,20      channels 169:6        choking 321:13
causing 12:20           126:19 129:2          243:21 244:17         173:16 180:21       choose 174:13
  15:11                 166:13 167:21         250:3,14,20         chaos 75:21           chosen 241:1
caveat 196:2 307:9      177:11 179:4          255:19 257:11       chaotic 83:2 84:6     Chowdhury 2:3 5:3
CDC 178:9 215:2         183:22 199:22         259:2 260:9         chapters 215:10         5:4 8:3 9:6 11:5
  298:4,9               212:19 223:20         264:14 266:6        characteristics         33:10,12 109:6
CDER 166:17             247:2 255:2 264:5     268:10 271:20         24:12 38:9 62:6       119:7,8 121:8,11
  167:10                306:7,8               273:2 274:11,22       127:2                 126:5,5 129:18
ceased 307:10         CFCs 15:10,16           280:5 283:18        characterization        227:20 229:12
cell 164:2,7            16:9 17:10 18:2       286:6,16 288:10       116:4                 241:12 249:6
census 78:1             19:6,8,14,15 20:2     290:9 291:11        characterize 184:1      269:4 273:2 275:9
center 5:11 44:8        20:7,14,16 21:2,8     292:6 294:20        charge 172:8            302:22 303:1,21
  59:17 94:1 132:2      22:1,7,21 25:21       296:5 299:8,12      Charlotte 205:21        304:22 306:9
  166:3 194:8           28:2 30:1 127:3       300:9,15 302:1,22   Charlotte's 223:1       307:2
centered 230:8          136:16                303:22 307:14       chart 20:22 21:2      Chowdhury's
  231:2,3,6,8,12      CFC-free 222:16         308:15 311:17         141:16                10:17 110:17
centers 114:12        CFC-propelled 1:6       312:17 313:22       cheap 63:11 73:19       115:16 124:9
  157:20 213:22         11:9 24:3 28:6,20     315:1 317:1         cheapest 152:19         229:1
  216:7,9,9,11          120:2                 322:11              check 55:1 69:3       chronic 83:3 84:12
  217:16 218:14       CFR 15:1 16:7         challenge 32:5,14       72:14 290:1           87:19,22 92:17
  220:14,14 244:10      17:18 22:9 23:17      141:11 179:18       checking 157:14         94:8,12 102:2
  295:10                303:6                 207:9 208:2,4       chemical 127:2          189:5 233:22
certain 174:17        chain 31:7 114:9,11     230:7               chemicals 17:12         273:15
  191:20 199:12         122:13 132:2,19     challenges 3:9 9:22   chemistry 15:15       chronically 34:22
  203:14 210:7          133:5 143:22          32:2 135:13 179:3   chest 7:17 34:20      Chung 72:21,22
  268:2 288:5 291:6     156:16 240:22         179:5 180:11,22       134:20 153:19,20      73:21
  309:18,18 313:20      242:4,5,10 244:3      185:15 201:16         153:21 270:11       Cindi 184:14,17,20
  315:13                244:9 297:15          210:15                277:7               circle 140:10 145:1


                                 Neal R. Gross & Co., Inc.
                                        202-234-4433
                                                                                                  Page 330

circuit 187:15        clinic 49:13 54:15       149:18                 136:17 142:21         134:21 142:22
circumstances           68:22 83:22          college 2:10 4:20        147:1 190:17          143:16 233:9
  99:21                 117:15 231:19          58:2 111:18 146:2      195:9 202:2         commonly 23:11
cities 148:19           243:20 275:4           273:7,22 274:4         203:19 206:22         23:12 24:9 32:22
  224:10              clinical 5:1,8 35:17     275:6 315:7            209:16 227:9          66:2
citizen 76:9            42:16 44:7 75:6      colleges 297:22          233:15 242:13       commonplace 67:3
citizen's 76:3          89:8 116:8,9         Collins 205:21           249:10 270:6        communicate
city 4:21 75:18         125:11 147:10          206:1                  276:11 306:10         138:7 141:21
  77:15 78:3 79:9       226:17,20 258:7      Columbia 75:14           307:6 309:7 310:2     144:11 158:18
  82:4 133:14           258:18,21 270:20     coma 93:4                310:16 315:16,19      186:15 256:14
  156:22 278:7          311:14               combination 54:2         315:22 316:1        communicated
claiming 42:21        clinically 47:6 98:2     60:3 64:6 72:11      comment 67:6            138:10 226:21
clarification 95:4    clinicians 318:1         72:22 73:2,3,4,8,9     69:12 71:20 72:19     227:2
  242:11              clinics 231:17,18        88:15,20               99:16 101:12        communicating
clarify 76:11         clip 204:5             combinations             104:9 105:14          154:22
  119:18 126:8        clips 171:2 289:9        59:12 88:14            109:7,8 110:13      communication 3:8
  131:22              clock 112:6            combined 60:19           111:16 119:9,10       3:9 9:18,21
clarifying 33:11      close 12:14 21:11        71:22 285:8            119:20 121:9          115:11 135:13
  94:18 165:19          28:4 32:1 219:11     combo 152:11,17          126:7 164:20          141:10 165:4,12
  233:1                 220:17,18 284:7      come 8:16 13:15          227:21,21,22          165:16 183:22
class 94:14 150:13      285:4                  31:19 32:18 33:14      234:8 241:12          186:9 299:10
  274:4               closed 187:15            42:19 68:19 69:2       242:6 268:17        communications
classified 36:13      closer 140:4             76:5 78:20 86:14       271:22 273:3          165:22 184:7
  39:21               clue 188:16              90:12,19 104:14        275:10 276:4          201:18,19 291:2
Clean 8:6 11:17       clued 245:22             104:16,21 108:2        286:10 299:9        communities 186:6
  14:22 16:7 17:16    clutched 41:11           109:21 120:12          303:2 304:4           216:11,14 217:16
  17:18 29:16,19      clutching 41:2           121:5 126:17           322:18                220:10,22
  261:5               CMS 214:1 219:14         135:16 138:9         comments 11:8         community 191:3
clear 27:6 42:7       CNS 57:22                142:6,15,22 156:9      41:1 73:11,11         215:5 216:7,8,9
  111:2 130:1 147:4   coalitions 291:16        158:16 159:1           126:9 186:7 207:8     216:11 217:15
  158:10 159:5,13       291:16                 163:10 167:7,13        222:4 223:1,11        220:21 291:16
  160:21 190:15,17    Code 72:1,13             172:16,18 173:15       242:20 261:22         295:10 298:3
  191:16,18 193:18    codes 310:5              181:3 184:20           275:11 300:15       companies 74:18
  204:2 231:1         codified 17:17 22:9      194:14 196:3           304:1 313:3,6         197:9 200:2
  257:18 258:5,17       25:5                   203:6 220:12         commerce 30:10          222:11 223:5,12
  269:5,9 271:12      cognizant 143:7          221:22 223:17          30:16 31:5          company 96:21
  274:13 275:1,12       162:8 222:17           227:5,13 232:15      commercialize           307:8
  284:3               cold 150:21 151:3        232:18 238:20          116:22              company's 9:18
clearly 40:19 52:4      196:9                  240:8 264:9 275:3    commitment 49:16      comparative 211:2
  56:22 57:6 61:16    collaborate 215:18       275:5 286:20         committed 113:2         211:6
  73:18 111:12          230:8 286:12,19        314:6,13               115:10 116:22       Compare 38:15
  140:15 226:20         287:2                comes 151:11           committee 22:15       compared 58:19
  227:2,11,18         collaboration            196:1 249:11           28:9 105:1 225:4      67:17 279:15
  236:10 284:9,18       186:12 213:12,20       271:14 312:12          241:17 298:18       comparing 44:14
  284:20              colleague 150:5        coming 6:10 9:3        committees 104:20       111:17
click 173:7             275:17                 12:19 16:9 21:14     common 34:21          comparison 68:6
climate 287:21        colleagues 72:15         97:22 130:16           42:11 66:19 69:17   compensated


                                  Neal R. Gross & Co., Inc.
                                         202-234-4433
                                                                                               Page 331

  206:11               244:5                 233:1,14 251:15       170:20 171:13,14    continue 63:12
compensation         concept 173:9         confusion 145:9         171:18 175:4,8        68:19 70:5 91:18
  193:15 206:16        267:4               Congress 99:11          180:6 181:10,14       122:11 282:13
competitor 250:5     conceptual 267:8        103:4 105:7 167:7     181:20 200:22       continued 41:20
complain 224:6,7     concern 11:22           201:21 212:7,11       255:6 276:12          92:16 94:7
complaining 297:5      188:20 254:14,17      319:19                290:21 300:18,22    continuing 40:7
complaint 239:18       254:21 269:19       conjunction 117:4       301:1 307:18          66:16 84:11
complaints 224:6       282:11 300:2          282:16              consumers 7:2 8:17    continuity 82:18
complement 115:2       304:15              connect 213:16          67:22 114:8         continuously 36:8
complementary        concerned 6:12        connected 322:5         118:19 133:9        contraction 38:10
  89:18                14:5 197:14         connection 298:6        164:21 166:12         38:21 39:3 51:11
complete 126:3         213:19 304:20       conscientious           167:19 169:21         51:14 267:13
completed 116:3        308:19                80:11                 170:13 173:6        contrary 43:1
completely 148:13    concerns 124:19       conscious 260:7         174:1,4 177:14        47:14
  259:6,18             151:9 194:20        consensus 8:16          179:3 181:18        contrast 36:7,21
completion 27:6        200:1 252:9 279:5     181:3 270:19          199:9 206:7           49:1 275:6
complex 256:21       concise 190:15        consequence 12:20       238:12 239:10,12    control 81:12
  267:14             conclude 112:2          14:7 38:4             254:14 289:4          121:20 233:8
complexities 137:8     303:11              consequences          consumer/patient        281:3
  138:22             concluded 212:6,6       13:16 14:10           270:4               controlled 43:5
complexity 138:17    conclusion 96:2       consequently          contact 80:7            54:13 58:7 75:19
  139:14 164:15,16     183:8                 202:17                183:12 194:2,7        95:6,7
compliance 83:2      concordant 226:19     consider 124:13         227:6,13 242:9      controller 203:2
  196:6              condition 100:19        181:16 194:13         243:10 247:13,17    controllers 202:21
complicated 97:16      200:20 235:21         248:22 254:8          247:17 256:10       controls 203:2
  104:14 127:17        236:3 296:4 309:9     255:11,13             257:9 292:22        conundrum 98:1
  138:22 294:8         309:12              considerable 122:2      293:21 295:8,16     convened 1:10
complications        conditioners 15:19    consideration           296:2 315:8           271:10
  54:14              conditions 100:4,6      27:17 128:18        contacted 195:7       conventional 63:5
complimentary          100:14,20 193:11      252:14,16 277:4     contain 122:2         conversation
  85:8                 308:22 310:15         288:6 296:11        container 118:2,7       278:12
comply 208:1         conductants 58:21       323:5                 253:17              converter 202:5
component 30:17      conducted 43:4        considered 16:4       containing 84:10      convey 8:17 284:10
  40:7 49:10 61:11     44:14 50:8 210:22   considering 133:8     contains 57:15 58:4   conveyed 256:1
  127:4 226:7          287:15                200:8               content 144:14          284:4
  280:14             conferences 170:11    consistent 79:15        219:3 220:8         cooperative 80:10
components 38:20       172:15 175:1          212:2                 226:12 227:3        coordinate 239:3
  61:8 267:14          181:14              Consortium 222:8        230:17 286:1        coordinating
comprehensibility    confident 124:7       constituents 175:21     310:11                298:18
  285:21               269:6               constriction 43:10    CONTENTS 3:1          COPD 20:8 133:22
comprehensive        confirm 237:11        consult 300:1         context 20:13           134:17 154:15
  92:22 204:22       confirmed 237:15      consulting 110:19       102:4 164:4           159:16,17,20
  205:3 293:12       confronted 209:22       111:12              contingencies           160:4 161:11
compressor 71:18     confuse 158:19        consumer 8:22           278:10                162:1 270:21
computers 180:19     confused 133:21         10:6 15:18 16:11    contingency 281:9     copy 72:1 171:14
COMT 48:13             191:17                31:9 100:14           321:4                 224:17 225:1
concentrations       confusing 232:8         113:19 144:7,9      continually 78:19     Cornell 2:10 4:20


                                Neal R. Gross & Co., Inc.
                                       202-234-4433
                                                                                                Page 332

cornerstone 37:3        17:1,3 19:9,15,22   crazy 265:10          customs 91:18          276:18
  39:16                 20:1,13,15,18,20    CRC 44:19             cut 159:13            dealing 151:2
correct 197:3 240:6     21:3,5 103:21       create 195:21         CVS 322:4,7            216:18 265:10
  257:14 262:7,18       251:11                220:21 285:11       cycle 249:15           266:3,4 283:5
  262:21 303:21       country 89:13           295:3                                     deals 268:7
corrective 195:12       114:21 132:13       creates 204:13                D             dealt 266:16
correctly 67:12         141:12 148:12       creatively 218:12     D 214:18              dear 150:5
  230:16 231:15         160:1 161:3,9       credibility 310:20    daily 37:21 235:17    death 41:13 42:9
  232:18 236:19         199:18 204:15       criteria 23:16,18     Dakota 114:14          56:16,19 193:9
  263:1 264:10          215:6,12 217:17       25:2,6,8,13,15       196:7                 204:14
  276:5 277:16          234:1 264:4 298:5     26:4 27:19 28:22    damage 14:2           deaths 42:3,5 57:8
correlate 187:2         298:8 311:6           29:7,9 38:3 44:21   danger 281:19          86:18,22 109:3
correlating 134:15      321:19 322:7          85:11               data 39:10 58:15       111:4,7
corticosteroid 40:5   country's 193:12      critical 18:18         66:14 76:7,18        debate 107:3
  52:6,17 54:1        county 65:16            292:10               84:14 85:22 86:1      108:13
  55:22 56:9,13,20      103:15 117:14       criticisms 46:21       87:11 91:9,11        decades 75:8
  61:19 64:4            298:7 299:1         Cross 186:14 187:6     94:5 98:22 109:21    December 6:19
corticosteroids       couple 10:17 50:4       187:8                111:2 132:22          23:13 24:2 28:16
  34:10,13 37:3         72:15 74:10 92:18   cross-over 44:12       133:1,2,3 141:13      28:19 30:6 31:19
  49:9 50:10 51:7       102:20 117:21         58:20                147:3 149:6 189:3     32:12,18 105:11
  55:10 57:10 61:17     121:19 149:19       crumpled 252:2         198:21 199:1,3        117:8 159:12
  61:19 63:14 70:10     150:20 163:2        crust 12:14            239:19 240:4,20       245:14 249:22
  202:21                192:9 209:18        cultural 18:19         241:1,8 242:6,12      253:13 303:8
cost 45:16 62:15        211:12,13 262:2     cumulative 26:3        244:16 312:7,15       304:19,19 305:3
  63:15 64:1 77:8       285:11,12 289:18      48:18                315:2,3               306:4 314:6
  120:12 121:15,20      296:2 297:9         cumulatively 25:21    date 27:13 31:12,13    320:20
  173:2 196:18          311:13                28:2 29:5            31:16,20 73:7        decide 101:17
  200:12 234:1        course 36:19 40:5     curious 65:20          140:10 234:17         167:4,10 168:22
  310:7                 49:8 63:12 90:5       66:11 68:3 122:10    245:14 284:12         169:2 170:2,7
costly 290:4            99:19 120:19          122:20 134:3         303:15 305:4          174:17 176:14
costs 63:6 161:16       175:19 178:5,20       135:1 246:9,22       306:8,19 313:20       260:7
  309:14                182:7 183:19          253:5               day 8:15 10:11 43:9   decided 28:19 93:2
cough 34:20 272:5       276:20              current 32:6,10        45:19 83:7 136:5      124:3 166:7 195:2
  272:15,16           cover 166:19            116:13 121:21        136:12 164:1          303:14
coughing 37:16          189:19 206:13         122:1 123:5 160:5    199:11 232:13        decides 50:1
  40:4                coverage 115:1,4        193:21 194:22        292:7                deciding 171:7
Council 5:14            122:8                 195:11 196:22       days 46:18 53:5       decision 18:3,6,9
counter 8:22 61:1     covered 61:7 238:3      209:2 251:8          60:11 80:20 83:7      73:12 110:18
  92:6 108:11 111:6     242:21 322:12         274:19 282:6         83:8 150:20 157:9     121:1 167:17
  144:8 152:9,16,18   covers 100:2          currently 6:21 33:7   day's 4:8              234:13 260:7
  158:12 175:5,13       189:14                114:9,12 181:11     day-to-day 56:11       275:15
  176:10 180:6        COX-2 315:12            248:8               dead 41:2             decongestant 88:13
  188:8 210:8 212:4   co-located 220:13     curriculum 220:2      deadline 124:10        88:16
  276:16 288:3        co-pay 64:11,13       curve 43:12,16,21      304:19               decongestants 95:5
  294:5                 141:17              custom 93:20          deal 65:6 99:9        decrease 54:12
counters 197:1,7      co-pays 64:8          customer 236:10        164:18 207:7          55:12,14 307:2
countries 16:18         198:14              customers 237:2        218:10 264:17        decreased 80:17,18


                                 Neal R. Gross & Co., Inc.
                                        202-234-4433
                                                                                                Page 333

 80:20                 239:20              detail 84:6 89:7      diagrams 146:18        directed 211:10,15
decreases 55:4        demographically      detailed 121:15       Diana 2:11 238:19        229:17 319:14
 56:14,15              258:3                 158:21 163:21         239:2 317:14         direction 176:7
dedicated 81:22       demographics         details 24:13 116:5   die 42:7 57:7            182:9 210:12
deemed 160:7           119:4 238:14          118:17                321:14                 213:3
deep 13:1             demonstrate 262:6    deterioration 52:10   died 41:10 87:15       directions 154:19
deeper 12:11           262:15              determine 34:6        difference 24:18       directly 211:16
default 260:8         demonstration          140:18 169:11         50:22 60:6,12          213:9 215:3 244:9
defer 131:16           81:2 204:13         determined 121:2        82:1 87:8 93:1       director 2:2,3,5,6
define 98:2 107:18     231:21              determining 165:5       96:11 97:4 98:3        4:14 5:4,10 166:2
defined 18:15         dentists 48:7        develop 116:22          133:21 167:15          195:7 206:9
 20:10 53:10          department 1:1         121:3 124:4           169:12 185:13        directors 223:10
definitely 190:8       65:16 80:6 81:5       144:13 170:3,5        199:4                  300:12
 227:4 298:13          82:8,11,19 103:16     173:11 176:22       differences 24:12      dirt 73:19
definition 18:13       117:15 229:8          182:5 215:19          46:10 185:1          disadvantage
 29:21 36:10 77:2      243:14 295:9          278:3 288:19          199:22                 271:22 272:17
 96:12                 298:8 299:2           291:2,5,9 295:5     different 34:4         disadvantaged
degraded 15:10        departments 191:4    developed 19:8,14       36:15 43:18,20         79:8
 48:13                 213:17 243:11         20:13,15,20 21:3      80:1 81:19 82:13     disadvantages
degree 105:3 265:9     295:16 298:5          125:8 200:10          88:13 110:22           107:5
 269:14                320:1               developing 20:1         123:1 127:3,12       disagree 307:16
delay 283:7           depend 115:14          32:7 168:20 171:8     136:10 146:2         disciplines 101:16
delayed 304:9          173:17                179:16 197:8          157:14,20 158:5      disclaimer 104:13
delaying 107:16       depending 63:15      Development 72:17       159:17 179:7         discontinued
deliberate 22:19       127:6 280:6         device 54:20            189:13 193:8           155:16,20 156:1
delighted 76:13        281:10 282:5          126:12 128:16,22      201:13 209:8           252:10,19
deliver 47:22 71:13   depends 306:4          129:4                 211:13 213:17,18     discuss 32:3 34:8
 87:4                 deplete 8:5 16:21    devices 29:20 68:13     232:17 233:12          79:21 117:16
deliverability        depleted 13:4,6        68:16 69:2 202:5      238:13 241:4           249:1 254:10
 116:14               depleting 14:14        266:2,2               243:7 262:9            285:14 291:8
delivered 44:15,16     15:2 17:10,19       dexamethasone           272:16 301:15        discussed 6:4
 49:5 55:5 110:9      depletion 11:21        26:19                 302:5,16 303:3,3     discussing 192:2
 210:5                 13:13 14:6 15:11    diabetes 93:1           311:5 318:9,19       discussion 3:12 6:2
delivering 116:15      110:7                 138:19                322:12                 10:8 27:7 104:17
 164:9 264:2 288:2    depletions 13:18     diabetic 93:4         differentiate 44:4       117:11 119:14
 319:14               Deputy 2:2 4:13      diabetics 92:18       differentiating          120:13 135:10
delivery 43:19 55:4   describe 221:10,12     93:3 105:21           267:9                  162:17 190:21
 70:17 124:14         described 28:8       diagnosable 100:19    differently 34:4         192:11 200:20
 125:5                 87:12 89:6          diagnosed 7:22          52:14 232:11           224:16 225:5,9,16
demand 114:16         design 44:12 58:20     105:21 154:6        difficult 71:4 179:8     227:9 238:9,16
 115:7 148:16          309:13                273:13 276:18         288:22 293:19          239:1,6 268:18
 305:20,21 306:15     designation 4:7        277:15              dilute 267:3             283:19 284:7
 306:16 307:5,5        23:15               diagnosis 35:10       dire 186:2               285:3,5 311:19
demands 137:8         designing 227:10       79:14 80:3 82:10    direct 5:7 188:12        312:1 323:3
 138:17,21 139:13     designs 44:4           204:8 237:12,14       213:10 245:7         discussions 135:20
 164:15,15            despite 315:13         270:20 271:4          260:13 265:5           199:21 241:16
demographic 133:7     destroy 160:12         274:3                 281:9                disease 39:11 56:8


                                 Neal R. Gross & Co., Inc.
                                        202-234-4433
                                                                                              Page 334

  61:10 87:3,19,22      209:16,17 320:21     317:6                66:13 67:4,5 68:7    244:18 245:4
  92:21 102:2         distributed 86:4,8    doing 110:20 122:4    69:10,13,15 70:20    246:12,18 247:9
  143:11 149:3          86:10,11,12 132:1    129:8 133:16         70:22 71:11,19       247:15 248:2,6,10
  201:9 233:18,19       148:12 230:2         139:14 149:9         73:13 74:5,13,22     248:14 249:5,6
  233:22 256:15,16    distributes 114:11     151:7 165:10         75:1,4 76:8,8,12     250:3,4,8,20,21
  258:12,19 265:1     distributing 244:9     174:3 175:2          76:15,17 79:10       251:3,9,14 254:8
  267:10,15 270:21    distribution 30:8,9    181:18 184:15        81:19 82:15 94:17    254:11,12 255:3
  270:21 273:15         30:15,18,19 31:6     197:11 214:16        94:19,19,20,22       255:16 256:4,6,7
  280:9 281:19          31:10 63:3 77:5      215:7 229:2,13       95:1,9,13,18,21      256:19,22 257:4,8
  283:8                 83:14 114:12         231:16 232:22        96:13,14,16,18       257:14,17 259:2,3
diseases 92:17          132:1,2 134:14       235:13 262:7         97:1,12,14,15,19     260:10 262:1
  94:12 160:6           135:3 187:11         309:18 311:4         97:20 98:6 99:15     263:5 264:14,15
  161:11,19 272:17      199:4 244:10         316:21               101:11 102:20,21     266:10,14,22
diskus 264:8            249:19 259:16       dominant 131:15       103:2 104:11         267:7 268:22
dispense 103:8        distributor 113:1     Don 58:13,18          106:6,7,11,12,15     269:4,8,9,11,19
  236:22              distributors 244:4    Donahue 55:16         106:18,21,22         271:15,20,21
dispensed 24:8        ditty 89:14           donation 30:20        107:17,21 108:3,6    273:2,3,4 274:11
  65:8 86:4           divide 37:10           31:2                 109:4,5 110:15,17    274:12,22 275:1,9
dispensing 232:2      division 2:2,3,5,6    door 104:18           111:15 112:18        275:10 276:9
  263:17                4:14 5:2,4,5,7,10   dose 6:16,18,22 8:8   115:16 117:20,21     277:17 280:5,6
displaced 295:20        66:17,20 72:16       8:14 9:16 43:12      118:9,13,14,15       283:12 285:6
display 254:4           105:19,20 109:17     43:16,21 44:5,10     119:7,8 121:8,11     289:12 290:9
disposal 10:4           115:16,16 166:3,6    44:17 45:22 48:21    122:9,10 123:10      291:11,12 292:6,7
disproportionate        166:16               49:12 57:22 68:15    123:11 124:8,11      294:20,21 296:17
  63:17               divisions 126:15       73:22 97:4 100:19    124:12,18 125:12     296:18 298:13,21
disseminate 7:9       doable 145:3           109:13,19 116:15     125:16,19 126:5,5    299:9,11,12,13,13
  8:19 92:3 163:9     doctor 7:22 62:19      132:18 196:18,22     129:14,18 130:19     300:7,9,10,10,13
  172:16 215:22         83:19,21 88:7        197:7 222:10         130:20 131:13,18     300:17 301:2
  216:4 296:14          151:18 154:6        doses 43:22 44:15     132:3,8,11 133:18    302:1,2,22 303:1
  298:1 299:7           156:3,14,15          48:17 50:12 51:18    135:12,14 165:18     303:12,21 304:8
  317:16                159:22 161:1         51:22                169:3,19 179:1       304:22 306:9,21
disseminating           237:10,11,20        dosing 114:1          184:13 185:19,20     307:1,2,14,15,17
  219:16 318:20         245:12 259:13       double 58:6 59:22     185:21 186:8         308:15,16 311:17
dissemination           261:17,17 272:13     60:16                187:19,20 188:7      311:18 313:7,8,22
  169:6 173:16          273:1 274:16        double-blind 50:9     188:16 189:9,11      314:1 315:3,4
  174:11 176:3,14       277:2 295:8,15      doubling 44:15        189:12,15,16,17      316:3,5,14 317:1
  180:20 182:18         308:4 321:20        doubt 105:9,10        189:22 190:1         317:1,3,9,12,13
  291:13 292:10       doctors 47:16         downloaded            223:21 225:17        317:17 318:21
  296:7,12,15 297:2     49:17 80:18 90:20    200:17               226:6 227:20         320:4,9,14,15,18
  300:16                134:2 180:9         Dr 4:16,18,22 5:3,6   228:21,22,22         321:6,7,9 322:3
distinction 12:16       243:18 259:11        5:13,17 6:6,8 8:2    229:12,19 230:5,6   draft 144:13
  302:8                 273:20 274:5         9:5,7,9,20 10:15     234:7,9 236:5,7     drained 307:11
distinguish 43:18       303:19 314:21        10:16,21 11:5        237:4,5,6,21        drastically 56:10
  43:22               doctor's 272:9         32:3 33:9,11,12      238:18,21 239:2     drive 172:22
distinguishes 37:13   doctor/patient         33:16,18 50:8        240:1,2,14 241:3    driver 233:22
  45:6,13               90:13                62:14,17 63:8,9      241:12 242:8        driver's 153:1
distress 151:13       document 85:17         64:15 65:5,19        243:4,5,22 244:17   driving 173:1


                                 Neal R. Gross & Co., Inc.
                                        202-234-4433
                                                                                                Page 335

dropped 45:2,4                E              266:16 267:2           198:9 319:4         employee 141:5,16
 47:13 111:7         earlier 16:10 22:10     298:11               Eighty 85:7           empty 93:10 197:3
drug 1:2 5:11 7:14     25:11 27:19 28:8    educational 8:21       Eighty-five 80:4        313:11 314:8
 23:11 32:22 33:2      132:21 173:21         10:5 31:17 206:6     Eighty-four 80:2      enable 44:4 93:13
 47:20 48:14,21        179:1 196:20          215:11,16 225:12     either 54:2,10,18       106:16 189:1
 54:17,22 55:5         212:5 254:2           268:6 312:21           108:20 117:14       enabling 237:2
 58:15 62:22 63:19     275:18 280:11         323:6                  119:6 315:21        encompassing
 64:12 68:2 74:8,9     283:17              effect 30:6,14 42:8    elaborate 96:15         18:19
 94:1 104:22         early 42:5 49:11        47:21 69:21 70:1     elderly 154:15        encounter 258:21
 108:10 110:8          50:6 90:1 307:10      70:1,11,19 73:19       214:19,21 220:12    encourage 223:12
 111:3 114:9,10,11   earn 42:18              98:19 116:16         electronically          252:15 319:15
 115:1,21 122:13     earth 12:2,14,20        183:1 228:16           153:2               encouraged 129:10
 125:6 127:8         earth's 11:20 12:14     257:2 265:19         eliminate 16:20       encouragement
 132:19 143:20,21    eases 7:19              305:19,20              17:9 18:2 193:9       159:4
 143:22 149:8,10     easier 27:1           effective 19:9 23:13     204:14              encouraging
 149:19 150:1,11     easily 212:22           24:2,22 25:7 26:6    eliminated 22:21        108:22 129:9
 150:13,15,17,19       224:10 237:22         26:22 28:16,19         129:17                233:16 301:14
 152:4,21 153:17     easy 181:21             29:12 32:12 42:14    eliminates 69:9       ended 152:6
 156:16,21 163:12    echo 223:1              46:7 57:19 59:10     eliminating 19:5      endless 309:5
 163:15 166:4        economic 74:17          61:4,14,15 73:17       21:22               endocrine 105:20
 176:9 207:4           186:2 245:1           87:4 100:20          Ellen 2:5 5:9 10:2    end-sets 99:17
 209:10 214:18         293:17                102:11 113:17          165:21 166:2        enemy 280:2
 240:22 242:4,5,10   economically 18:21      116:1 196:19           183:13 266:8        engaged 136:11
 244:3,9 246:14,15   economics 74:14         201:11 213:12          288:18              engagement 209:9
 246:16 264:2          98:7                  221:15 222:15        Ellen's 288:13        England 42:6
 266:4 270:16        ED 299:3                269:3 288:20         embellish 235:7       English 149:1
 297:15 302:12       edema 38:11,22          297:1,7 303:8        emergency 40:17         177:15 181:10
 307:21                51:10                 308:2 310:7 317:8      40:20 45:8 50:3       200:10 251:1,5
drugs 42:3 43:18     educate 7:1,7 113:5   effectively 33:4         51:4,17 68:10       enormous 203:12
 88:13 103:3           167:8 247:17          54:19 67:7,16          80:6,19 81:5 82:8     311:8
 104:10 122:13       educated 53:6           68:1,5 124:20          82:11,18 87:5       enroll 214:2
 167:9 287:9           180:10 188:11       effectiveness 211:2      116:2 151:18        entertain 73:14
druthers 262:22      educating 3:10 4:6      211:7 227:1            156:18 190:7,12     enthusiastic 129:10
dry 68:17 129:15       166:12 177:13       effects 14:1 48:20       190:16 191:3        entire 31:6 58:17
 129:18 130:2,10       179:3                 57:21 58:1 59:11       243:11,14 278:6     entities 76:16
 264:6,12            education 10:13         63:13 116:18           282:9 320:6 321:6   environment 14:2
due 7:18 193:10        36:10 37:7 39:6       125:2,21 269:14        321:7                 16:4 19:1 136:13
 204:15                54:20 62:2 66:16    efficacy 34:14 50:9    emergently 227:16       141:3
DUGAN 224:20           67:14 68:6 133:12     58:11 89:8 116:13    emission 13:12,12     environmental
dumb-bells 313:14      166:7,16,21 167:5     316:1                Emory 2:9 4:16          2:13 11:3 17:6
Duram-Humphrey         168:11,20 169:1,4   effort 81:7 169:11       9:20 142:1            109:11 247:3
 96:7                  174:14 178:12         183:21 267:2         emotional 215:15        298:15
duration 47:5          179:20 182:15       efforts 167:17         emphasis 183:2        enzyme 48:11
 113:14                184:16,18 203:11      223:14                 244:20              eosinophils 38:12
dying 34:1 53:9        218:13 230:8        egressing 125:21       emphasized 266:17     EPA 11:17 14:22
 57:2 86:16 104:5      232:22 239:4        EIB 300:12             emphasizing 268:2       183:16 203:13
 202:19 209:20         255:4 263:8         eight 56:2 83:7          272:22                215:3


                                Neal R. Gross & Co., Inc.
                                       202-234-4433
                                                                                                 Page 336

EPA's 29:16 30:5       Eric 1:17             event 109:21 113:5    exceptions 189:18       164:22 224:4
ephedrine 57:16,17     especially 42:12        239:18 279:3          195:10                278:19 285:22
  59:4,6,12,15 60:2      57:18 191:3           306:6               excessive 38:13       expiration 93:17
  60:2,7,18 72:3,12      209:16 214:10       events 108:19           39:1 51:10          expired 255:7
  88:20                  229:5 265:16        eventually 41:21      excessively 235:17    explain 14:16
epi 184:8                307:20 323:2        everybody 4:5 6:9     excludes 29:20          247:2
epidemics 42:5         ESQ 2:12                11:6 90:18 119:21   excluding 86:12       explanations 48:3
epidemiology           essence 163:8           120:9 136:4 137:2   exclusive 84:21       explore 164:10
  148:1                  285:15 308:1          161:14 173:17         85:2                explored 129:16
epinephrine 1:6        essential 4:7 18:13     192:16 232:10       excuse 201:20         exposure 282:5
  3:5,8 4:8 6:15         18:15,15 19:11,16     259:8 262:12          238:18              Express 322:2
  7:12 8:8 9:8,16,17     20:2,9,10 30:3,4    evidence 39:10        exempted 20:9         expressing 317:10
  11:9 22:5 23:1,7       61:8 143:1 145:14     93:12 108:4         exemption 19:17       extend 188:7
  24:20 28:5,6,15        159:2 226:9 302:6     142:13 143:2        exercised 273:6       extended 35:19
  28:21 29:11,13         302:7,21 303:2,7      144:21 145:7        exhibit 170:10        extension 119:2
  30:2 32:11,21          303:16,17 316:20      226:13,14,16          289:3               extent 170:17
  34:9 40:10 42:14     essentiality 25:14      285:7 296:3         exhibits 174:18         216:2 235:10
  43:7 44:16 46:6        26:5,21 27:13,18    evidence-based          185:8                 283:4 293:3 314:2
  46:21 47:6,12,17       28:14 29:21           226:17 258:15       exist 95:12 101:20      318:3
  47:19 48:5,8,13      essentially 11:18     exacerbation 34:14      106:13 147:6        extreme 283:14
  51:13 60:14 61:3       15:3,17 16:9 17:9     34:22 35:2 41:21      148:8 149:6 154:9     293:5
  61:14 73:1,3           17:14 18:4,11         90:1 190:9            173:19 199:17       e-mail 183:10
  85:20 86:6 91:1        20:5,14,22 21:14    exacerbations 41:6    exists 25:17 125:3      298:6
  92:4 99:1 105:15       26:1 30:7 48:20       55:12                 241:8
  109:9,13 111:17        57:4 72:7 127:11    exact 73:7 108:14     expand 30:11,15,16              F
  120:3,15 125:8         228:7                 162:18 241:20         237:6               face 9:22 107:15
  128:4 129:3          established 210:19      249:7 298:16        expanded 274:14       faced 208:4
  166:13 167:21          214:8               exactly 118:1 153:3   expanding 17:21       faces 253:17
  173:5 178:8 179:4    establishments          220:7 249:16        expect 203:6,7        face-to-face 180:9
  183:19 185:14          188:5                 306:18              expected 31:20        facilitate 311:4
  210:18 225:14        estimate 114:6        examining 50:9          116:6               facilitating 109:1
  228:4 238:12         Estrella 223:18,19      55:17               expensive 121:16      fact 9:2 23:11 42:3
  250:10 275:19        et 308:10             example 15:18 40:6      121:18 230:15         47:21 57:4 58:10
  276:7 280:10         etcetera 57:14          63:16 95:16           232:3 310:22          71:7 72:5 74:13
episode 40:21            264:8                 119:18 127:19       experience 68:21        75:20 104:1 120:2
  41:15,22 53:10       European 21:3           167:9 170:7           69:11,22 70:12        129:20 165:15
  281:10,22 282:5,7    evaluate 43:5 103:6     171:20 172:20         194:12 232:9          170:14 171:21
episodes 114:1           169:22 316:17,21      173:10,20 176:8       264:7 265:9 275:2     201:4 204:9
  198:16,19 281:4      evaluated 54:5          178:7,19 189:18       288:7 315:12          226:14 252:10
episodic 190:9           271:2                 233:3               experienced 198:16      254:3 263:17
  232:6                evaluating 35:8,14    examples 13:20          206:20                276:10 289:5
episodically 154:16      68:9,11               92:18 171:9 176:3   expert 37:8 39:9,12     291:14
equally 148:13         evaluation 2:6 5:8      178:10 218:18         144:15              facts 7:15 152:21
  285:8                  5:11 166:4 169:7    excellent 87:2        expertise 271:3         153:17 246:14,15
equals 240:10            169:10,17 234:21      94:20 177:21          309:10                246:16
ER 207:19 311:15         258:21 284:15         181:19 222:22       experts 142:15        factual 226:15
ergotamine 26:20         312:18 314:9,11       298:14                143:18,18 147:5     fail 90:9


                                  Neal R. Gross & Co., Inc.
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failing 140:8            288:1,16,19 290:4     156:19 322:7           306:17                 246:1 260:16
failure 52:12 104:6      296:9 310:20        fill 53:5 64:3         Firstly 126:13         follow 25:13 102:9
fair 99:13 186:18        317:6 322:13        filled 55:20,20 56:2   fiscal 292:7             111:14 119:10
Fairfax 193:6            323:4                  56:21 57:1,3        Fishers 1:11             133:7 242:9 249:7
fairly 107:10 224:9   FDA's 8:3 10:3         filling 53:15 263:14   fit 149:11 278:21        277:17 303:22
  234:12                 14:22 17:18 173:7   final 22:18 28:10      fits 244:19              316:16
faith 186:19             198:20                 28:11,19 72:11      Fitzpatrick 184:14     followed 314:18
fall 14:16            fears 200:1               73:12 164:20          184:21 244:1         following 26:14
falls 15:4 140:2      feasible 18:21         finally 193:11         five 38:5 78:12 83:7     86:1 119:17 169:2
  141:7               features 34:5 35:7        215:2                 83:8 85:14 114:17      183:17 192:10
familiar 39:8           37:9,12              financial 65:4           128:5 131:7,10,10      195:12 283:16
families 78:18,20     federal 72:1,13           143:8 146:12          131:14 132:5,6       fonts 253:20
  78:20 79:1,2,3        77:3 93:16 99:10        148:3                 193:20 197:6         food 1:2 186:19
  83:15 84:7 191:9      193:21 201:20        financially 64:21        224:12 226:10          187:11 207:4
  199:11 200:12         223:4                find 32:6,14 42:19       232:17 301:8           209:9
family 77:1 83:1      fee 216:12                51:20 72:10 93:15   fix 279:7              force 24:6
  315:8               feed 291:14               93:21 94:1 144:6    flag 188:8 289:20      foreign 278:7
Fanta 50:8            feedback 184:17           148:10,20 149:5       289:20               forget 47:16 298:15
fantastic 221:3         322:15,19               149:21 158:1        flat 43:12             forgiving 129:2
far 29:1 33:22 74:2   feel 40:2 122:17          163:12 164:11       floor 126:6            form 59:2
  84:17 120:7           200:18 270:4            187:18 194:10       Florida 2:9 5:2 9:7    formal 222:4 223:4
  129:11 147:9          282:1 283:6 310:6       195:1 220:16          41:9 42:17 66:15     formally 255:21
  159:8 245:13          321:14 322:19           221:2 224:2 239:5     81:21 95:17 104:1    formed 16:17
  280:1 304:20        feeling 179:12            240:18 243:1          114:19 189:18          222:8
fascinated 204:11     feelings 302:2            245:7,18 253:6,7      275:2                former 198:17
fascinating 239:6     fellow 50:8               273:8 287:14        flow 38:11,17,18       formulated 128:9
fatal 40:22 41:15     felt 315:14               311:10 312:8        flu 150:21 151:2,3       128:11
  41:21 52:20,20      fever 100:17              313:10,21 319:7       151:8,15,21          formulation 29:3
  53:10 109:2         Fewer 82:4             finding 16:3 245:2     fludrocortisone          116:5,14 121:6
favorite 150:14       field 250:2               285:11 309:13         93:8                   123:20,22 125:2
FDA 2:1 4:5,10 5:8    fifth 140:16           fine 262:11 270:5      fluticasone 26:19        127:5,7,8,9
  5:12,15 8:10 10:2   figure 79:20 86:17        282:2 304:20          27:10                  128:18 129:1,2,15
  11:15 17:20 22:11     97:8 102:17          finer 116:5            flyers 219:3             129:19 130:2,5,11
  29:22 33:20 58:5      134:10 136:6,21      first 8:2,21 22:14     focus 163:11 207:8       130:15 264:1
  60:21 76:4 90:20      138:1 141:16            34:3 36:19 48:5       216:21 267:6         formulations
  92:2 111:12 116:9     143:12 144:10           50:8 54:16 82:1       272:8 285:11           126:15
  118:4 135:15          145:19 158:2            86:9 112:2 113:4      287:4,15 299:20      forth 107:4 213:17
  165:22 167:10,14      159:2 161:17            119:20 120:2,17       312:10 316:6           247:4 285:18
  171:12,13,17          162:8 163:8 165:1       124:13 131:8          319:16,16            Forty 79:12
  177:19 181:19         244:21 258:14           136:14 142:11       focuses 78:15          forum 219:9
  192:4 203:13          265:17 272:18           150:10 182:15         266:12               forward 10:11
  204:1 206:17          314:2                   195:14 201:16       focusing 137:22          33:21 121:1
  211:16 213:11       figures 86:13             203:11 211:15,17    foil 125:20              122:18 129:8
  215:17 217:17         315:20                  223:21 225:11       folk 224:2               207:4,11,12 208:3
  220:20 222:21       figuring 246:20           236:6 249:20        folks 6:3 159:17         225:8 234:12
  228:10 274:14         269:22                  250:1 256:8           169:14 172:22          276:2 296:11
  285:10 286:12       file 66:6 88:9 116:6      295:14 304:10         187:17 224:5,11        305:15 322:20


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found 41:2,10 56:1    function 35:9,22      20:2,21 22:4        global 15:4 17:5        169:2 228:9
  79:18 125:4 151:5     36:1 38:4 44:10     50:14 54:11,17        20:19 130:15          259:18 281:3
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foundation 146:3        56:13 141:2         147:16 158:9        go 4:4 10:19 17:22      238:3 312:22
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  206:13              fund 220:21 221:8     169:13,14 172:13      28:17 29:15 33:3      100:7 129:11
foundations 221:7     funding 168:14        173:4 175:22          38:6 41:3 53:4,17     135:18 137:9
Founder 193:4           172:3 176:21        183:6 188:18          54:21 64:15,22        158:11 175:9
four 14:12 16:2,15      203:17 211:1,6      201:18 235:19         67:5 70:21 74:1       191:13 244:11
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  114:1 118:19          162:17 182:18       273:19 278:14         100:18 101:5          6:19 7:3 8:1,2,11
  147:2 154:20          183:10 239:12       282:11 287:4          103:5 105:21          9:21 11:12 17:10
  155:2,5,7,16          310:10 322:17,21    291:12 297:13         108:20 112:3          20:6 24:19 61:5
  229:11 240:7,10     future 251:4 277:4    302:11 303:20         123:3,5,21 130:17     65:15,17 72:14
  240:16 280:21         316:10              304:16 312:4,5        135:7 137:4           75:2 78:11 102:8
  282:14 296:19                           give 5:18 11:10         142:17 143:20         102:10 104:5,12
  301:8                        G            31:1 33:19 44:10      149:10,22,22          110:2,9 112:12,15
fourth 18:7 140:16    gain 5:21 84:18       49:13 62:14 63:12     151:18 152:18         118:3 121:20
framework 137:19      gap 162:4             75:2 89:14 104:1      156:20 157:1          122:18,19 123:5
  138:15 139:9        gasping 321:12        104:12 139:15         161:18 162:10         125:20 129:7,12
Frank 2:5 5:9,9       gather 224:10         140:13 146:6          164:13 167:4          135:12 136:16,21
  10:2 165:21 166:1     293:12              156:17 158:21         168:10 169:16         137:17,18,21
  166:2 289:15        geared 174:2          162:14 172:14         170:9,11 171:3        144:22 145:1
frankly 206:18,21     gearing 214:1         176:4 179:5,14        173:14 175:12         147:9 148:17
  207:9 292:15        general 70:9 166:5    233:2 249:16          186:17 187:5          150:2 151:21
  293:14 302:13         166:15 174:12       294:13 295:9,11       188:2 190:3 191:1     152:12 154:22
free 35:20 54:13        176:17 189:20     given 16:12 32:5,21     195:2 199:1 210:9     155:22 157:9,20
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  206:5 229:3,10        264:19 265:15       134:13 141:21         218:15,16 219:21      161:17 163:9,19
frequency 37:11         280:1 288:16        147:22 148:1          220:11 221:7          164:22 166:5
  55:12 60:6            305:14              160:1 181:14          230:18 235:8          168:12,13,22
frequent 53:18        generalists 217:14    186:21 190:2          237:10 238:5,21       169:6 170:3
  304:14              generally 171:5       300:5 320:7           239:19 244:15         171:10 173:14,17
frequently 36:9         277:20            giver 207:18,22         255:5 259:12          174:17 175:5,10
  52:21               generic 57:13 72:4 givers 214:20,20,21      268:9 270:22          179:16,18 180:5
FRIDAY 1:8              88:16 110:22      gives 94:15 295:13      275:9 277:21          180:19 182:10,11
friend 71:1             167:9 176:8         296:2                 280:12 283:2          185:8 190:3,6
friends 79:5          genesis 11:12       give-away 30:20         285:19 287:5          192:1,2,17,19
front 158:11          gentleman 239:16    giving 130:21           295:10,19 298:2       196:7 202:11
  224:19 253:17       geographic 134:14     246:6 307:7           299:1,16,20 301:3     207:8 208:17
fronts 213:20           148:3             glad 62:10 73:13        307:15 310:1          210:2 211:12
frowning 256:17       geographically        216:2 239:6           315:20 320:21         213:4,11 215:8
fruitful 10:11          310:4               241:14 311:2          322:4                 216:6 220:17


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                                        202-234-4433
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  234:4,17 237:10       245:10 250:9          195:20 215:5,11     handy 212:22        33:5,6 35:14
  237:19 243:17,18      258:15,16 266:7       215:18,19 217:16    hang 252:8 295:13   42:12 47:15 65:16
  244:3 245:19          269:4 273:5           221:20 285:12       hanging 210:14      75:14 85:22 86:1
  246:10,10,21,22       278:14 280:2,3,4      286:11 287:4,15     happen 30:13        90:17 99:8 103:14
  246:22 247:6          287:7 290:6           291:17 312:10        31:20 66:6 74:12   103:15 113:19
  249:2 251:19          300:13 309:20         316:6                91:20 103:5 113:7  117:14 132:21
  252:10,13,22          312:11 323:3        grown-ups 78:9         126:22 193:13      133:1 136:12
  253:12,16 256:9     gosh 151:22           GSK 63:2 65:7          234:17 260:19,22   137:6,10,10,18
  260:12,17 261:2,3   gotten 75:13 87:5       223:7                287:14 294:10      138:14 139:17
  261:8,10,16           111:21 225:1        guaifenesin 57:16      300:5 321:3        141:2,3,4,6,17
  264:20 270:5          310:11                58:4,7 71:22        happened 23:4,4     142:8 157:20
  279:17,20 284:11    governing 18:5          72:12 73:1,1,3       76:4 108:17 120:7  161:3,8 164:4
  287:9,16,22,22      government 93:16        152:12               130:5,12,18        174:3,4,22 185:6
  288:1 290:17,18       94:2 111:5 201:20   guarantee 262:11       287:11             185:8 191:4,8,10
  292:18 293:8,11       213:14              guess 97:20 109:7     happening 148:18    198:13 202:20
  294:3,10,15,18      governs 17:19           149:13 234:9         175:10 232:1       206:7 210:6,9
  295:7 298:2         grade 140:16            241:3 261:6 273:1    234:16 267:9       214:3 216:7,8,9
  302:11,15,17        gradual 305:10          281:7 306:21         281:4 321:17       216:11,12 217:15
  304:9 305:15,19     gradually 306:21        314:1 316:18        happens 13:6 20:15  218:11,15,19
  305:20 307:4        graduating 94:14        322:9                126:20 231:22      219:7 220:14
  309:21 310:10,18    granted 246:21        guidance 197:5         306:12,12          222:18 229:8
  312:10 314:13,20    graph 21:9              277:13              happy 114:5         230:2 234:1
  316:9 317:4 320:2   great 6:8 89:7        guide 35:10 204:17     208:21 209:8       237:12 241:7
  321:14                118:13 131:19         242:1                211:20 213:13      242:16 256:10
golden 165:11           164:3 187:18        guideline 85:11       hard 101:7 103:22   257:10,15 258:4
  230:6                 191:8 192:1         guidelines 37:7        152:22 171:14      263:2,10 266:21
good 4:3 6:9 11:2,5     202:14 204:10         39:7 40:12 49:8      172:10 204:16      270:1 271:3,11
  12:9,18 33:18         219:19 223:2          53:18 89:20          232:4,9 246:19     284:14 293:21
  39:21 47:4 68:19      231:5 254:11          204:18 205:6         253:6 261:15       295:9,10,16 298:5
  90:22 92:21           281:14 308:7          208:10 229:22        262:13 315:6       298:7 299:2
  101:18 112:21       greater 50:19 53:9      317:16,19,22        harder 165:3        300:14 305:9
  116:19 124:8        green 233:4             318:2               hardest 165:15      307:19 308:20
  132:8 136:7,15      grocery 186:4         gum 48:8               231:6              315:9 320:1
  140:1 141:9         grounded 145:16       guys 106:1 224:5      Hardwick 222:3     hear 8:2,22 9:5,14
  146:19 148:5          226:16                                    Harlem 71:2,8       12:13 73:13 75:9
  149:12 160:18,19    group 47:11,12                 H             218:18             107:7,19 146:4
  160:22 161:10         50:18,19 52:4       half 71:7 77:7 78:7   harmful 16:4        147:20 204:1,1,3
  163:3 164:9 166:1     78:11,14 80:10       79:21 86:9 114:1     HARWICK 222:2       208:21 211:20
  174:15,18 176:16      81:8,13 124:9        118:20 321:21        HCFCs 17:11         219:22 242:2
  179:14 181:15         138:8 142:12        halons 17:11          head 162:13 187:6   249:14 263:2
  187:13 190:15         163:11 217:22       hand 49:15 98:11       299:14             268:12 269:5
  191:6 203:16          222:10 260:13        128:17 130:13        headlines 139:22    318:2 320:5
  206:1 207:6,20        298:15 299:3         297:11               heads 301:6        heard 42:15 77:8
  210:7 214:19          316:11 318:10,12    handing 229:21        head-nod 305:11     116:1 155:16
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                                        202-234-4433
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hearing 104:8          257:14 263:5        home 39:15 49:15       50:17,22 51:20     identify 103:13
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 291:7,20 304:8        300:13 307:14,15      315:6,10 321:22     household 139:18    ignore 80:22 162:7
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 47:17,18,21         hesitate 134:1          82:17 186:1         HRSA 295:17            189:5 282:6
held 14:7 18:8         183:11                188:14 243:8        huge 21:15 262:8    illnesses 94:8
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help 72:19 95:7      HFA 115:12 116:3      hook 272:10           HUMAN 1:1              222:12
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 217:18 230:4        HFAs 264:5              182:11 206:12       hyper-tension          221:4
 231:14 236:18       HFA/MDI 63:7            207:11               138:20             immediately 278:6
 240:2 241:22        HFA/MVI 62:19         hopes 8:10            hypotheses 147:10   immigration 149:1
 293:11 311:3        HFC 222:15            hoping 113:6 142:5    Hypothyroidism      immune 13:22
 319:7               Hi 183:15 222:2         168:18               93:6               impact 8:7 23:6,9
helpful 179:16       high 11:20 12:7,17    Hopkins 2:12          H1N1 142:5 151:2       110:9 198:9
 212:21 213:8          19:3,4 49:12 57:2     10:22 282:19         186:10                316:21
 223:13 224:11         68:14 77:4 107:20   horizon 164:5                             impacted 221:1
 241:6               higher 12:6 13:17     horizontal 21:13               I          impacting 110:8
helping 199:14,15      78:13 164:8         hospital 50:5 56:5    ibuprofen 98:12        229:15
helps 199:20         highly 195:5            59:17 63:3,16         99:19 101:5       impending 52:11
 265:18              Hispanic 195:5          93:22 108:2         ice 225:18          implement 318:11
Hendeles 2:8 4:22    historically 128:3      147:12,15,17        idea 13:11 18:2     implementation
 4:22 9:7 33:12,17     129:22                236:1 243:20          19:4 23:6 25:9       317:21
 33:18 62:17 63:9    history 7:11 11:11      282:8                 54:21 58:6 73:14 implementers
 65:5 66:13 67:5       14:13 23:21         hospitalization         89:19 93:19 120:5    318:5
 68:7 69:15 71:11      101:13 109:5          55:15 56:15 80:20     137:6 176:4       import 31:9,14
 73:13 74:13,22        113:16 120:18       hospitalized 55:18      187:18 206:22     importance 116:20
 81:20 94:19,20        193:12 280:11         81:4 282:18           219:2 236:8       important 6:11


                                Neal R. Gross & Co., Inc.
                                       202-234-4433
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  25:19 26:2 28:1       267:2 311:20        industry 15:18          299:7 301:13,16       271:7 278:2
  32:20 35:7 37:9     included 23:18          197:5,6               309:15 310:21         279:10,15 287:17
  40:14 46:19 49:9      59:4 132:22         ineffective 68:15       318:20 319:9          320:6 321:18,20
  52:13,15 60:17        218:18              infarct 100:11        informative 239:5     inhalers 6:16,18,22
  61:9,11 115:17      includes 30:20 31:9   infection 282:6       informed 248:19         8:14 42:15 66:1,4
  131:1 142:7           86:3                inferior 207:14       informing 6:12          67:17,18,19,20
  143:15 146:11,18    including 11:12       infiltration 38:12    infrequently 57:1       68:15,17,18 71:5
  158:16 159:1          15:20 16:18 17:11   inflammation 37:2     Ingelheim 223:19        86:16 109:13
  160:13 161:14         31:7 62:6             267:13,19           ingredient 99:22        142:21 147:21
  167:11,14,22        income 77:1,5 83:1    inflammatory 40:7       152:15                155:13 156:12
  168:3 186:11          83:9,15 85:6          61:11 82:7 256:16   ingredients 60:4        159:11 173:5
  190:6,14 191:1        214:6 216:14          280:13 308:21       inhalant 312:12         195:17 197:2,8
  203:4 212:12          219:2 258:8,13,17   influenza 104:2       inhalation 1:6          199:22 223:20
  216:16 224:3        incomes 77:7          inform 134:11           11:10 19:17 20:7      225:14 229:4
  229:3 238:10        incomplete 39:21        151:8 158:8           23:10 24:21 28:7      231:16 232:2
  241:5,13 252:12       40:1                  241:10 242:14         28:15,21 29:13        233:11,20 236:13
  253:21 269:21       incorporate 146:16      253:4 279:19          33:1 228:4            261:13 264:6
  270:3,18 276:12     Incorporated 86:2       294:18 309:6        inhalations 282:18      266:2
  278:12 284:2          86:3                information 5:19      inhaled 34:13 37:3    inhibitors 315:12
  285:8 295:19        increase 53:14          8:3 67:14 86:2        38:1 41:17 45:15    initial 126:21
  297:8,20 301:5        54:10 57:22 58:8      94:1 113:20           45:17 49:7 54:1       241:17 249:12
  307:22 310:14,17      90:3                  118:16 119:2          55:10,22 56:9,13    initially 16:18
  312:11 322:1        increased 111:4         130:21 132:19         56:20 57:9 59:2,4     280:9
importantly 61:22       229:16                134:4 135:5,19        61:19 62:4 63:10    initials 298:16
impossible 83:4       incredible 135:18       138:13 148:6          63:14 64:4 70:10    initiated 49:11
improve 55:13         incredibly 131:6        158:21 159:7          85:20 86:5 90:4     initiation 54:9
  80:12 92:11 263:9     138:22 203:16         167:18 170:21         90:22 91:1,14,21    initiative 16:5,14
improved 50:18          310:14                173:4,8 178:5,17      92:3,4 96:3 99:1      218:19
  208:22              IND 116:6               178:22 179:14,21      123:14 264:2        inject 47:17
improvement 46:5      independent             179:22 180:16         273:5 280:21        injected 60:14
  50:19 56:12           114:10 122:13         181:21 183:9          308:6               inkling 239:20
improvements 62:5       143:21                187:22 190:15,22    inhaler 8:9 9:16      inner-city 80:12
  200:9               index 89:4,5            194:4 206:5 207:2     41:3 44:17 48:22      81:18 82:14 186:5
IMS 85:21 86:1        India 89:11             215:12 219:4          55:2,4 62:18 67:7     195:4 243:10
  132:21 133:1        Indian 89:11            224:3 226:15          67:8,16 71:9          293:16,20
  241:2               indication 7:15         227:4 229:21          73:18 87:14 92:10   inner-urban 243:9
inability 265:21        40:4 96:9 279:1       238:6,13,15           96:19,20 98:4       innovator 72:4
inactived 48:15       indications 100:3       239:10,11,12,22       109:19 115:20       input 144:15
inadequately 88:2       100:10,11,12,15       241:20 242:1          117:1 127:4 156:9     282:13 285:10
  88:6 91:7,22          116:12                243:2 244:5 246:3     156:15 166:13         286:17 312:20
  94:10               individual 144:17       246:6,17 247:19       167:21 178:9          318:13,14,19
inappropriate           210:13 232:12         248:18 249:1,2,11     179:4 183:22        insert 117:5 118:3
  68:14               individuals 221:18      249:17 250:7          188:15 208:6,6        118:6 233:12
incentive 74:18         243:16 249:3          251:17 253:7          217:5 222:10          254:6 294:11
incentivized 195:21   indoor 200:9,11         286:18 290:17,18      232:14,18 260:14    inside 137:9 147:15
include 13:20           298:15                293:1,13 294:14       261:18 262:19,21      147:17 164:17
  214:11 223:5        induced 273:6           296:13 298:7          263:22 264:12         294:16


                                 Neal R. Gross & Co., Inc.
                                        202-234-4433
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insight 62:15 107:6     140:18              investigators 15:14   IV 50:15,15          82:17 147:21
insights 135:2        intermittent 35:18      89:13                                    156:5 191:11
insist 64:11            36:3,5,15,17        invitation 76:10                J          195:8 196:11
inspired 222:5          37:11 65:12 85:3    invite 238:19         Jacob 131:16,20      220:11
  223:22                134:17 235:1,13     invited 76:5          Jake 250:11        kind 13:21 76:6
instance 81:8           237:17 278:20       inviting 33:19        Jane 270:4,15        93:2 133:5,11
  214:14                281:18 311:21         206:2               January 19:9 24:22   139:9 150:22
Institute 2:11          315:18              involved 101:16         25:7,12 26:6       151:20 155:17
instituted 202:9      internal 160:17         146:3 169:17          196:8 249:22       156:10 158:17
instruction 111:20    internally 133:6        214:16 297:14       Japan 21:4           167:16 172:5
instructions 67:9     international 17:2      318:5               JD 2:4               173:8 182:8 184:2
  200:12 233:12         109:12 222:7        involvement 22:19     Jewish 59:17         186:7,12 190:2
insufficiency 93:8    internet 85:13,15     involves 38:9         Jim 55:16            208:8,12 209:15
insufficient 273:18     89:1 164:8 170:19     168:13              job 165:5 202:14     210:1 220:9 226:2
insulin 92:19 93:3      185:5 194:16        in-house 171:3          203:16 311:16      234:9 235:4 238:1
  93:5 101:12           200:17 289:7        IOM 137:20 231:5        317:8              245:7 246:17
  105:18 106:5        Internist 4:19        IPAC 222:6 223:3      Joe 270:4,15         252:2 255:4,21
insurance 115:1       interpret 315:20      IPAC's 222:13         Johns 2:12 10:22     268:10 272:10
  122:7 141:6,18      interstate 30:9,16      223:10              join 10:18 70:22     274:8 284:6 286:8
  198:13 214:3          31:5                IPAC-RS 228:15          194:3              308:10 314:11,17
integrated 197:7      intervene 53:6        ipratropium 26:20     joining 29:7 239:8   317:5 321:3
intellectual 18:19      137:21              irrational 73:9       journal 89:9       kinds 55:3 157:20
intended 63:3         intervention 52:5,7   Irvine 15:8           journals 89:12       166:15 197:4
intensive 53:12         80:16,17 81:1,8     isopreterenol 60:14     177:17           kit 200:10,11
intent 122:17 123:3     81:12,13            isoproterenol         justified 23:15    knew 197:13 272:7
  305:8               interviewed 85:7        60:10 128:5           27:18 29:2,8       272:20 315:15
interact 66:16        interviewing          issue 22:5 33:21                         knocked 104:18
interacting 158:13      150:16                86:15,18 94:9                 K        know 7:3,5,6,8,9
interaction 291:19    intrigued 135:16        95:14,15 101:22     keenest 151:9        23:10 43:9 62:16
interest 44:2 134:8   introduce 6:4           104:14 108:14       keenly 148:4         65:21 67:2,18
  175:21,22 296:6       10:20 33:14 222:1     109:10,11 110:7     keep 29:22 48:7      69:22 70:4,12
  298:10                223:16 238:22         120:11 123:21         49:15 109:16       72:19 73:5 74:14
interested 104:8      introduced 113:18       124:2 125:20          137:22 145:1       84:14 85:17 86:22
  105:5 108:12          120:19                130:15 161:2          149:10 251:20      94:15,16 98:9
  148:4 183:3,4,6,7   introductions 4:10      162:7 211:8           261:7,20 264:21    101:1,7 103:17
  183:17 260:17       Introduction/Bac...     234:12 241:11         284:22 296:9       105:1,8 106:2,4
  292:22 296:16         3:4                   247:3 260:11          318:13             107:5 108:12
interesting 42:1      introductory 11:8       293:17 301:19       keeping 113:2        109:4,6 115:2
  87:21 89:2 95:22    intubated 53:11       issues 32:2 92:13     keeps 48:10          118:21 119:21
  104:17 106:13       intuitively 233:3       102:6 126:8 161:5   kept 157:21 159:16   121:16 122:16
  155:17 219:16       invalid 312:16          161:16,16 216:18    ketoprofen 99:18     123:18 129:6
  223:11 247:10       inventory 188:1         216:19 264:18,21    key 92:13 138:3,6    131:2,3,6 134:4,5
  317:5                 248:9                 265:2,21 266:1,5      144:4 158:15       134:13,16,18,19
interface 266:19      investigate 89:15       266:15                184:15 194:16      135:14 136:3,5,7
interfere 97:10         129:6               item 3:2 112:13         217:22 256:5       139:6,12 141:21
interim 117:2         investigated 212:9      260:1                 269:22             142:20 143:9
intermediate 140:1    investigating 106:1   items 284:6           kid 140:8            144:1,8 145:4,15
                                                                  kids 75:16 81:6

                                 Neal R. Gross & Co., Inc.
                                        202-234-4433
                                                                                             Page 343

146:22 147:8         271:9 272:2,4,9               L             195:13,16,21          255:3 256:19
148:1 149:21         272:12,18 273:1,4   label 118:7 134:19      196:14 203:21         257:4 260:10
151:16 152:1,1,7     273:12 274:16,21      140:20,20 153:17    layer 8:5 11:21         266:10,22 271:15
153:2,10 154:4,21    278:11,18 279:17      155:4 245:5,9,13      12:4 13:11 14:9       277:17 283:12
156:10 157:1,7,11    280:11,19 281:8       246:15,16 247:2       15:12 16:21           301:2 316:14
157:12,15,15,16      281:21 282:14         247:12 250:17,19      158:22,22 279:21      317:9 318:21
159:13,18 160:14     283:9,11,16           251:4,11,15         Lay-Health 218:20       320:9,15
161:15 162:3,6,14    284:20 285:19         252:17              lead 70:3             Les 75:5 87:12
164:7 172:5 177:8    286:2 287:12        labeling 7:21 88:17   leader 184:15           89:20 91:1 98:22
179:11,20 185:17     288:8 289:18,20       100:1,9 117:5       leads 109:2             107:1,22 111:16
186:8,21,22          289:21 290:5,7        118:5 119:11        League 300:18           267:22 273:7
187:16 188:5         291:18,22 292:2       211:18 247:20       learn 8:10,13 92:14     280:19
189:13 190:10,13     292:16,21 293:2,4     248:9 249:22          135:21 136:4        Leslie 2:8 4:22
191:12,13,15         293:10,11,18          250:21 254:2          150:15 175:10       lesson 111:13
194:1,11 195:8       294:9,13 295:1,7      271:17 274:14,19      277:9               lessons 184:6
196:10 197:10,15     295:17,19,22          290:16 292:12       learned 111:13          185:18 203:10
197:17 198:20,21     298:19 299:15,16      299:22 305:18         145:21 184:6,12       317:14,18
199:10 200:20        300:17,21 301:1,7     314:5                 184:19,22 185:17    letter 308:10,11
202:20,21 203:7      302:6,9,14,20,21    labels 149:9 154:8      186:22 203:10       letters 175:1 178:3
204:7,12,18,20       304:9,13,18,18      lack 34:14 82:17,18     207:6 213:22          178:4,13 181:22
205:16,17 209:6      306:16 307:5          87:21 148:22          279:8 316:1           181:22 182:2,6
210:1,2,19,20        309:5 311:6         lacking 148:2,2         317:15,17             218:7 289:6 297:1
211:2,5 212:1,7,8    312:15 313:9,12     Lane 1:11             learning 175:22         297:19 301:14
212:13,19 213:6      313:15,19 314:5     language 23:17        leave 94:12 145:5     letting 119:21
214:4,8,13 215:20    314:12,13,14,15       148:22 162:19         286:3 321:22          203:7
216:4,7 217:4        314:18,19 315:19      250:22 278:21       led 107:9 108:19      let's 77:13 88:11
219:21 221:2,3       315:19,22 316:5,9     309:1               left 21:10 165:3        97:10 102:17
223:3 224:2,5,8      316:17 317:8,21     lap 72:2                197:22 207:16         195:2,6 218:3
225:19 226:15,18     318:1,11,12,14,18   large 13:5 23:8       left-hand 12:1          221:9,11 238:5
227:2 230:22         319:2,5,12,17,22      24:6 70:5 142:4,5   legal 96:11             255:20 256:2
231:4 233:5,6,19     320:5,12,20 321:2     156:16 167:3        legally 97:8            262:19 288:11
234:11,22 235:7,7    321:13,16 322:3       186:14 187:11       legend 117:6          levalbuterol 223:8
235:10,15,17        knowing 97:21,22       300:18 308:11       legible 254:5         level 53:13 77:3
237:3 238:11         121:5 148:4 234:3   larger 14:8 17:4      length 256:18           83:9,15 109:22
239:9 240:7          246:1,5,7 272:1       79:19               Leonard-Segal 2:6       133:10 140:17
242:18 243:1         306:18,19           largest 17:2,3          5:6,7,18 6:7,8        179:20 210:9
244:22 245:6,9,16   knowledge 65:6,9     lastly 34:14 62:7       10:16 67:4 70:20      253:22 291:15
246:9 247:2,7,20     104:19 121:15       late 217:1 222:8        71:19 74:5 76:8     levels 215:6
248:2 249:18         218:10              lately 151:2 213:13     76:15 95:21 96:14   lexicon 134:21
252:3 253:14        knowledgeable        laugh 142:14            96:18 97:12,15,20   LIAWATIDEWI
254:14 255:3,10      98:7 101:15         law 17:17 25:5 26:7     99:15 104:11          131:20 132:4,9,17
256:17 257:19       known 60:16 120:4      95:11 96:5 97:10      106:7,12,18 109:4     135:4 250:12
258:11 259:10        120:9 131:4           97:15 99:2,5,7        184:13 185:20       libraries 219:18,20
260:11,15,16         193:21 208:9          101:16 109:12         189:9,12,16           220:6,15
262:13,14,17,18      214:4 240:6           195:19                246:12 247:9,15     license 153:1
263:3 264:3,15,22   knows 160:9 262:6    laws 11:14 14:18        248:2,6,10,14       licensed 207:17
265:12 267:12,18    Krissy 41:9            16:14 26:13           249:5 254:12          208:18


                               Neal R. Gross & Co., Inc.
                                      202-234-4433
                                                                                                   Page 344

lies 12:5              lists 26:17 88:13       lo 150:20 151:3         58:14 65:3 124:16     260:21 265:21
lieu 309:21            listservs 297:18        local 48:7 215:6,9      125:11 126:15         266:18 267:7
life 36:5 62:6 83:1    literacy 137:6            291:15,16 292:5       128:7 130:7           269:14 272:22
   193:8 195:17           139:17 141:4           295:10,19             131:14 133:19         280:20 292:5
   198:16,18 255:17    literally 30:21         localized 48:8,10       154:21 162:5          293:22 295:20
   281:13 282:4        literate 137:18         locate 154:14           186:1,9 188:20        298:17 322:14
light 12:10 233:4      literature 42:4         located 179:15          194:14 196:14       lots 90:8 187:22
limit 13:12 226:10        81:11 84:19          location 66:11,11       205:13 218:22         295:11 317:18
limitation 95:14          110:21 147:4           148:3                 220:8 234:11        loud 269:5,9
limitations 35:11         273:21               locations 309:19        238:14 273:17         275:12
limited 123:8          little 5:19 7:11 40:2   lodge 116:17            295:22 300:19       love 107:7 143:4
   149:15 168:12          48:19 62:15 75:11    long 19:10 39:13        305:10 313:5          146:7 149:9 150:6
   169:9 232:4            80:18,19,20 81:9       54:2 58:3 65:14       320:22              low 12:13 45:4 83:1
   302:15 309:4           89:21 112:5            99:20 115:18        looks 118:10            85:5 200:12 214:6
   313:5                  118:15 134:14          116:18 120:4          301:21                216:14 219:2
limiting 125:17           136:2 146:18           124:2 207:22        loratadine 189:19       244:22 292:3
   272:19                 147:3 149:22           208:9,14 255:8      lore 89:17            lower 70:18 116:15
line 15:22 36:19          151:6 152:6            278:19 294:6        Los 133:15            lunch 10:7 192:6
   61:2 143:9 146:4       156:10 162:3         longer 6:18 46:16     lose 96:22 163:7      lung 2:11 35:8,22
   161:22 181:7,8         166:9 169:8 175:2      46:16,20 49:19        209:4 244:12          38:4 44:10,20
   237:18 249:4           175:7 179:7,8,11       225:19 250:13         278:1                 45:2,21 46:2,6,13
   296:15 313:5           187:15 192:5           251:19 256:9        loss 235:9              47:2 48:12 50:17
   316:16 321:16          202:5 208:13           283:11 284:11       lost 79:3 156:8         52:10 55:13 56:12
lined 139:2,7             210:2 226:3            320:8                 321:18,19             308:21
lines 21:16               232:11 238:2,7,16    look 10:11 21:10      lot 15:17 57:21       lungs 54:17
link 29:15 214:5          274:7 288:21           41:3,14 42:3 58:6     59:9 66:3 67:10
linked 52:19              289:22 312:7           59:5 78:14 79:6       67:20 76:20 95:22            M
linking 219:1             313:4                  81:1,7,14 83:6        105:4,7,8 129:10    magazine 171:14
list 27:11 64:12       Liu 2:12 10:21,21         88:11 125:1           133:4 135:21         172:6 176:19
   148:15 170:4           69:11,13 106:21        129:21 132:13         145:7,7,8 146:1     magazines 170:9
   171:6 174:16           106:22 107:21          140:1,5 146:11        146:21 149:12        176:15,18,22
   177:12 182:16          108:6 118:14,15        152:20 153:11         150:10,15 151:1,7    177:2
   190:3 212:22           129:14 234:7,9         161:4,7 169:1         154:17 156:21       magnitude 221:9
   231:4 256:2            237:6,21 264:14        170:3 174:16          157:18,19 158:10    mail-in 263:20
   270:22 288:13          264:15 266:14          178:7 195:14          160:20 163:10       main 35:17 260:11
   289:18 295:18          267:7 268:22           196:10,16 201:10      168:14,14 172:2      284:9
   303:8                  280:5,6 292:6,7        206:22 207:1          172:15 178:16       mainstream 175:15
listed 13:19 24:13        299:14 302:1,2         217:11 224:11         180:1 186:8 191:4   maintain 122:5
   25:14 27:9,19          303:12 304:8           225:8 233:7 253:8     194:12,18 199:3     maintained 45:18
   29:1,7 40:11 95:4      307:17 317:1,12        253:19 254:2          200:1 201:16        maintenance 46:19
   257:8 288:21        live 79:4 141:19          259:10,15 268:7       202:16,17 205:12     53:20 76:1 84:11
   303:7                  149:16 157:19          287:10 300:20         210:16,20,20         87:18 92:16 93:10
listen 277:10             165:10 224:6,11        313:18 318:5          211:5 216:18         94:7,11 102:2
   285:18                 227:14 298:22        looked 56:18 59:11      217:8,11 218:9       189:6
listening 165:13,16    lives 75:21 84:6          152:7 153:14          225:7 231:10        major 6:13 42:17
   185:21                 198:10                 262:3                 235:21 238:13        69:10 81:7 101:21
listing 27:5 212:16    living 87:10 164:1      looking 33:21 44:3      244:20 253:7,19      114:9 171:8


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                                          202-234-4433
                                                                                           Page 345

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majority 77:11       294:8 305:2,14       244:12               98:2                 321:10
 194:1,6 198:13     manufacturers        materials 169:5      meanings 303:3       medically 30:4
 201:7 272:20        120:6 204:3 223:7    173:18 182:21       means 18:7 19:13      97:11
maker 9:15           228:13 229:11        185:10 214:12        26:1 29:8 30:12     Medicare 139:20
making 26:8 29:12    231:13 232:20        250:19               30:21 31:13 40:2     213:22 214:18
 73:12 74:1 83:12    233:16 234:3        matter 27:7 112:10    83:20 107:21        medication 24:10
 108:21 169:11       236:9,12,17 237:1    192:14 204:21        140:5 144:21         24:20 70:8 80:5
 188:10 191:10      manufacturing         323:8                154:16 160:20        86:20 87:14 91:19
 222:18 227:10,18    31:7                matters 232:12        228:7 281:15         108:7,15,16 115:3
 231:8,8 271:3      man's 58:1           Maureen 222:3        meant 29:22 140:6     189:14 194:8,14
 278:17 292:11,14   Mapquest 172:21      McFadden 50:7         233:6                197:1 208:19
 294:22 295:1,2     maps 196:14          McLean 79:11         measure 35:22         234:19 235:11
 302:15 320:2       Marcus 2:10 4:18      82:15                44:10 59:19          236:4 266:13
malls 170:18         75:2 188:13         MD 2:2,3,6,9,10,12    169:12 314:19        274:10 287:21
manage 161:11       Mark 2:12 10:21       82:10                317:7                294:1
 268:3 294:4         94:21               MDI 39:18 48:2       measured 45:21       medications 173:1
manageable 267:14   marked 46:5 62:5      69:9 71:13 113:10    47:8                 194:15 195:9
managed 217:12      markedly 50:18        124:21              measurement 46:2      196:1 199:12,15
 236:1              market 24:4,17       MDIs 69:5,6          measures 195:12       199:16 200:7
management 90:2      31:15 62:9 109:15    196:17 198:11       measuring 35:8        202:17 212:3,13
 92:22 107:16        110:3 115:9 120:3    222:16 238:12       mechanism 128:21      212:17,19 213:1
 234:22 264:18       120:8 123:6         mean 29:17 30:7      mechanisms 127:5      230:15 294:3
 265:1 270:10        142:21 148:16        36:3 67:2 69:21      127:13               300:4
 273:15 277:12       150:9 186:5          96:20 108:11        med 115:20           Medicinal 89:3
 281:3 284:15        198:11 237:11,19     132:6 144:19,19     media 42:2 170:22    medicine 4:17 41:5
 291:8               242:14,15 246:10     148:7 155:3 156:6    175:14,17 177:20     82:5,7 84:10,22
managing 194:5       250:15 253:12        160:19 161:2         210:1 214:12         85:9 86:4 93:11
mandate 274:18       255:1 270:7 271:8    187:1 208:12         288:16 292:19        94:13 101:16
mandated 201:21      271:14 279:20        209:19 231:16       Medicaid 71:16        116:21 140:19
 202:10 274:15       292:19 309:8         233:5,10 234:13      188:21 189:13,18     146:8 160:17
 277:2               310:16               235:17 241:13        189:20 205:4         189:6 221:15
Manhattan 71:3      marketed 27:3         246:19 258:5,9,13    214:1                226:18,20 256:12
 75:17               115:6                260:10 265:12,14    medical 2:10 4:20     257:2 284:16
manifestations      marketing 23:21       265:15 266:11,15     15:20 17:21 20:9     311:15,15
 81:15               120:18 131:17,21     266:18 267:11        29:20 40:20 75:12   medicines 60:16,17
manipulate 68:1     Mart 65:18 86:5,13    269:13 270:22        75:15 80:7 82:17     77:9 161:22
manner 60:1         Martha 2:4 5:13       272:15 276:17        89:9,12 92:12        222:11 230:10
 124:10 185:16      Maryland 1:11         280:12,22 281:11     93:12 96:12          315:14
 248:20 306:6       mask 52:10,11         283:13 293:5,19      102:10 104:6        medium 163:18
manufacture         masks 69:8 71:12      301:18 302:10,12     114:22 143:10        164:10
 222:11             mass 170:17           302:16 303:16        150:12 151:10       meet 29:21 137:14
manufactured        Master 75:14          304:12,18 305:3      160:8 161:10,12      219:6
 116:10             match 25:9            306:10 314:10        161:21 225:21       meeting 5:20,21
manufacturer        matching 65:2         317:10               243:8,13,16          18:7 22:16,17
 112:22 135:9        153:21              meaning 66:5          258:22 277:13        26:4 27:8 28:10


                               Neal R. Gross & Co., Inc.
                                      202-234-4433
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 76:6 102:6 138:11    216:15 228:2         128:4               Mirax 59:13 60:4      109:19
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 206:18 219:10        253:14 255:4        metered 6:15,18,22   mission 193:9         116:6,7
 223:1,10,12          257:13 258:5         8:8,14 9:16 44:17    222:13              monthly 57:3
 241:18 297:10        261:21 262:14       metering 127:5,12    Mist 41:11,13,19     months 35:20
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meetings 18:8         265:22 267:4,15      124:14 125:5         54:22 59:8 64:18     81:6 110:17 198:8
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 213:13               270:14 271:13       methods 43:19         194:21 198:4         281:22
melanoma 13:21        272:8,19,19          83:3 296:13          203:1 237:9         month's 64:13
members 2:1 194:3     275:13 278:8        methyl 17:11          245:21 250:5,12     Montreal 8:4 9:6
 201:5 322:13,15      283:20 284:3,7,13   metoproterenol        255:17 272:2         11:13 14:13,19
 322:16 323:2         284:16,22 285:5,7    107:2 128:8          275:5 314:20         15:4 16:17,19
membership            285:10 286:7        metric 21:12,19,20    318:15               17:7,15 18:1,4,16
 298:19               288:2 292:9,14      microphone 33:14     mistake 270:14        19:7,19 21:22
men 259:12,13         293:8 296:14         223:17 286:21       mistakes 67:11        25:10 126:13
mention 137:18        298:20 299:18       microscopic 152:22   mix 48:8              130:7 222:9 261:4
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 216:6                307:16 315:22       middle 44:9 45:1     model 17:5 43:7      morning 4:3 5:22
mentioned 32:4        319:15 320:20        45:10 78:9 139:5     133:12 233:21        6:9 11:2,5 33:18
 65:20 118:15        messages 8:19 10:5   Mike 59:10 223:18    modeling 133:18       46:11,13 104:2
 169:3,19 173:21      34:2 138:3,6,8      mild 36:4 65:12      models 41:9           112:2,21 165:21
 178:19 179:2,9,10    142:8 143:2,13,15    153:19 237:16       moderate 38:1         166:1,5 201:1
 180:14 181:17        144:2,5,12 145:14    278:20,20            79:15 82:9           207:7 225:10
 182:14 199:13        149:4 158:17        mile 157:1,5,16      modify 313:1          228:2 289:16
 275:21 282:15        159:2 162:12,20     milligrams 57:15     moiety 26:11         morning's 5:17
 289:16,20 290:5      162:21,21 164:3,9    58:22 59:7          moisture 126:4       mother 71:5
 299:4 306:14         165:6 175:11        million 24:7 74:16   molecules 26:15      Mothers 192:22
menu 171:6 174:12     180:15 181:3,4       85:14 86:7,11        27:9                 287:1 319:1
mercy 172:6           187:16 191:8         113:22 114:2,4,7    moment 124:7         motivates 238:14
Merena 72:21          208:15 214:7,11      114:21 118:19,20     209:12 307:19       mouth 291:17
message 7:9 8:17      216:20 218:2,7       147:2 240:7,10,16    308:8,19            move 22:3 28:3
 32:11 60:17 61:2     219:17 226:2,4,5    mind 104:21          moments 204:7         33:12,16 74:21
 61:9 92:2,8,10       226:9 230:9          110:13 295:4,5       319:10               110:19 112:13
 142:13 158:15        234:14 238:2,8      minds 270:15         money 42:18 65:14     121:1 122:18
 161:14 163:8,10      255:20,22 256:3,5   mine 71:1             98:9 168:14          135:7 192:17
 165:2 166:11         260:3 261:14        minimum 83:6          188:19,21 199:1      207:11,11 224:18
 167:11,15,22         267:3 271:11        minor 100:16          205:12,13,18         255:21 268:11
 168:3,10,17,21       284:1 301:4,19      minuses 105:8         235:22 309:4         284:8 288:11
 169:4,15 170:1,1     310:17 314:10       minute 57:17 75:12    310:12 311:7         296:6,11 299:8
 171:17 172:7,10     messaging 202:14      112:8 138:16        Monkey 197:20,22      314:19 322:20
 174:7,18 175:17      287:2                249:8 307:1          201:4                323:5
 176:6,12 177:1,21   messengers 203:20    minutes 11:7 33:10   monoamine 48:16      moved 20:14 31:21
 180:13 183:6        metabolic 105:19      37:2 39:17 46:1,1   monograph 72:5        255:20
 188:4 191:16        metaproterenol        46:2 113:15          72:11,18 74:4       moving 170:22
 203:14 210:5,13      109:5 110:22         137:16 167:1         99:22 105:17         208:3,5


                                Neal R. Gross & Co., Inc.
                                       202-234-4433
                                                                                               Page 347

MPH 79:11              119:5 120:7,7,19     237:19 245:11          247:20 273:12,16     13:21
mucosal 38:11,22       124:8 306:5          246:1,3 255:11,22      275:3 278:21        non-ODS 275:19
 51:9                 NDAC 104:22           260:3,7 271:2          283:22 285:4         276:7
multiple 14:21 24:1   near 52:20 53:10      272:12 277:12          289:9 290:16        non-profit 205:11
 120:12 249:10        nearly 146:19         280:12 281:12,16       317:18 321:20       non-sedating
municipal 77:14       Nebraska 195:3        284:10 288:5         newer 207:15           189:19
muscle 38:10,21        196:13               293:3,6 308:3,4,5      278:22              non-selective 60:9
 39:3 51:11,14        nebulizer 39:19       313:1 318:14         news 42:2 140:1       non-steroidals 99:4
 267:10,12             71:18                319:19 322:20          149:13 171:2        non-traditional
muscles 7:20          necessarily 36:4     needed 186:17           173:21 174:1         218:14,22
music 149:12           125:6 128:14         202:6                  178:1,13 181:17     normal 36:2 38:15
mutually 219:15        129:1 130:1         needing 53:11 84:9      182:2 218:7 297:1    47:3
                       162:18 180:5         87:17 102:1            297:18 301:14       normally 100:2
         N             185:15 218:15       needs 49:10,20        newspaper 41:12       Northern 71:2
NAEPP 204:17           280:12 294:2         52:5 100:18            172:6 177:5,7       note 26:9 40:14
 205:6 229:22         necessary 12:8        138:10 142:19        newspapers 170:9       42:2
 298:18 317:16         18:17 69:18          161:14 165:8         Nguyen 2:4 5:13,13    notes 197:20
name 4:13 10:21        292:16 302:21        188:20 196:4         NHLBI 239:5            296:18
 72:6 93:11 110:22    necessitating         237:9 253:14         nice 172:19 245:19    notice 211:18 223:5
 166:1 193:3 213:2     207:17               292:1                  302:20               301:10
 222:2 223:18         need 7:1 10:14       negative 12:20        night 37:15 44:9,19   not-for 206:4
names 57:14            34:10 46:16 52:16    13:16 14:1,6,10        45:1,11,20 55:11    not-for-profit
Nancy 192:20,22        52:17 53:19 61:18   neglected 110:21        58:3                 221:7
 193:3 205:19          74:1 75:21 84:5     negotiation 19:19     nights 49:18          NSAID 100:15
 206:11                92:14,15,18 93:5    neighborhood 71:2     nighttime 111:19      NSAIDS 100:3
NAPP 40:11             93:7,8 94:6 98:21   neither 58:8 105:17   NIH 49:7 53:17        number 55:9 68:8
Naproxen 99:18         100:5 103:14        nervous 151:6,20      nine 16:16 198:6,17    75:12 107:22
narrow 168:1           109:16 123:14       nested 148:11         Nobel 15:15            111:6 118:22
 174:20                128:13 138:3,19     network 187:5,9       nocturnal 43:8         183:11 186:18
nation 168:4 193:7     138:21 139:2,3,6     192:21 287:1           44:6                 195:19 198:15
 196:11                139:7,14 141:1,3     298:4                nominated 21:8         201:16,17 209:7
national 2:11 36:10    141:4 143:16        networks 186:14       non 97:2 98:15         212:17 213:20
 37:6 39:6 59:17       144:1 145:11,14      215:5 291:15           113:11 193:5         239:18 245:18
 62:1 79:20 80:10      146:9 151:16         292:5                None-Prescription      246:13 247:13,17
 109:12 172:1          158:2,16 159:15     Network/Mothers         105:16               253:13 261:21
 182:2 206:4 239:3     159:22 160:8,21      193:5                nonprescribed          282:18 284:10
 263:7 297:14          161:1,18 162:1      never 145:8 198:4       108:7                287:16 302:13
 298:11 299:5          167:11 168:9         200:4                nonprescription        308:11 321:11
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nationally 65:3        180:1 181:1 188:4    69:1 74:8,9 75:17      42:13 43:6 57:12     76:18 77:17,22
 142:6                 191:1,15 194:13      77:14 78:3 79:9        62:7 68:4 72:16      79:19 141:18
nationwide 170:5       200:8 203:22         82:3 93:15 103:18      88:12 91:15 92:20   nurse 54:7 59:18
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nation-wide 167:4      217:11 225:21        122:11,21,22         non-CFC 121:1         nurses 49:17
Nature 15:13           226:16,18,20         133:14 188:14        non-compliant          191:10,12 195:3
NDA 96:22 105:17       227:4 232:15,16      197:8 203:6 217:5      205:5               nuts 309:3
 109:18,20 113:18      232:18 235:5,18      220:5 243:9          non-melanoma


                                 Neal R. Gross & Co., Inc.
                                        202-234-4433
                                                                                               Page 348

          O            70:21 95:13,18,18   operates 11:18          198:22 205:9        outrage 111:8
objective 315:2        95:20 96:13 97:1    operating 19:20         297:12,22 298:9     outreach 166:8
obligations 14:17      101:11 104:11         20:11                 319:1                 195:7 201:11
obscure 163:20         106:11,18 112:12    opinion 62:8 97:21    organizations 99:9      203:12 205:14
observe 265:7          121:10 131:18         160:15 269:18         167:12 175:20         214:2,16 215:7
observed 54:15         132:3 140:11          289:10 304:21         178:13 182:3,17       220:21
obstacle 45:17         142:1 150:19          307:8                 186:17,19 199:13    outside 118:3
obstructed 38:17       153:14 154:2,19     opinions 193:16         205:11 296:19,22      129:20 167:12
obstruction 38:18      155:3,18 156:3        304:5                 297:10,18 299:5,6     182:17 206:16
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obstructs 38:10        197:21 221:22         175:16 205:10       orient 18:7           outsized 214:9,22
obtain 91:16           223:16 224:8,12     opportunity 41:14     original 79:10 84:2   overall 33:3 303:17
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obtained 242:7         251:15 262:12         205:8 209:4 230:7   osteoarthritis        overlapped 226:3
  322:14               309:7 320:14          231:13 232:21         100:12              overseen 105:18
obvious 233:3          321:7                 233:17,21 234:3,6   OTC 7:14 10:5         oversight 161:12
  302:3              old 35:3 46:17          270:13 290:13,22      32:5 67:8,18 74:4   overwhelming
obviously 70:2         58:15,15 67:18      opposed 50:21           74:4,8,9 84:17,21     138:18
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occasional 153:18      280:7               opposite 220:7          87:14 88:11 96:6      68:13
occasionally         older 69:7 106:4        312:8                 96:7,8,12,20 98:5   over-arching
  147:14               155:5 259:13        oppressive 136:20       100:6,14,15,18        308:18 311:13
occur 36:18 54:14    olds 78:12            optimal 70:17           101:12 102:16       over-the 8:21 60:22
  86:19              once 30:1 47:1 61:2   optimistic 98:17        105:14 108:4          92:5 111:5 144:7
occurred 50:13         68:18 204:7           101:18                109:15 113:2          276:15 294:4
  195:11               254:14 264:11       option 164:7 177:3      115:16,18 116:21    over-the-counter
occurring 312:14       299:22 301:21         177:10 290:5,6        150:9 155:13          6:15,21 7:13 8:8
occurs 49:3 113:13   onerous 22:12         options 10:3            194:15 196:12,16      32:21 55:7 61:4
ocean 208:13         ones 104:21 106:8       146:15 166:10         196:22 197:13,15      86:20 92:19 98:13
ocean's 14:3           138:5 144:21          170:4 181:8 300:6     198:4,7,10,17         98:18 103:12
October 301:17         152:17,19 159:10      309:21                199:15 200:7,19       107:9,12 110:16
  307:10               162:4 176:18        oral 34:15 40:4         201:9 204:20          111:3 113:10
offer 30:8,18 48:2     186:15 188:4          49:8 50:2 58:22       221:11,11 260:13      132:18 153:7
  161:15 212:16        197:9 203:21          59:10 61:20 62:7      261:8,9 268:19        160:2 180:4
  215:15 216:12        273:21 283:14         71:8,22 74:19         271:17,18 277:18      189:14,21 207:16
  218:12               288:20 297:9          87:6 90:5 269:16      278:9,13 279:1        208:22 210:17
offers 206:5,6         316:8               orally 57:19 73:16      283:15 284:21         212:14 228:4
office 2:4 5:14      one-third 133:8         269:12              OTC/CFC-prope...        270:7 294:1 300:4
  105:16 165:21      ongoing 124:6         orciprenaline           225:13                312:13
  263:20 266:20      online 219:3            111:1,6             OTC/MDI 193:22        over-use 279:11
  272:10               254:19,21 319:9     order 145:15          ought 243:13          over-using 42:8
offices 213:17       open 3:11 10:7          210:11 241:9          259:20 311:19       owner 119:5
official 242:9         22:16,17 128:21       242:14 254:19,21    outcome 93:1          ownership 30:21
off-label 100:22       192:8,19 205:20     organization 90:21    outer 117:6           oxidase 48:16
oh 151:22 156:7        221:19                186:13 193:6,14     outliers 265:15       ozone 8:5 11:20,21
okay 26:3 33:16      operated 26:13          194:2,3 195:15,20   outlining 286:9         12:4,6,12,13,15


                                Neal R. Gross & Co., Inc.
                                       202-234-4433
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         P            179:1 186:8         partnered 298:11       52:15,21 53:4,18     penny 63:10
package 117:5         189:22 190:1        partnering 205:16      54:5,16,21 55:1      people 7:7 8:22
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pact 63:2             240:14 241:3         186:17 187:13         63:18,22 67:22        77:11,14,17 79:8
pad 290:2             242:8 245:4          212:10 220:22         68:18 69:7,16,20      79:9,22,22 85:2
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pains 100:16          276:9 285:6          93:20 189:2           146:5 154:13          102:8,15,17 105:4
pamphlet 140:15       289:12 294:20,21    patency 51:1           159:17 164:21         107:19 109:1
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panels 278:18         136:1,8 144:4        35:19 36:7 37:4       224:4 228:3 232:9     147:12,13,15,16
 280:7 285:12         165:12,15 185:12     38:17 39:2,20         243:9 259:22          150:17 151:1,14
panic-mode 314:7      192:18 200:18        40:17,20 43:10,20     272:21 275:3          154:2,14 156:1,2
paper 82:16,22        205:16 214:18        53:8 54:20 55:14      277:21 282:19         156:4,8 157:18,19
 85:13                224:16 227:7,10      64:2 65:13 67:15      283:14 287:4,6,15     158:5,19,20
paradigm 280:8        228:8,8,17 229:14    68:9 69:1,3 87:11     298:22 308:3          162:10,11,22
paragraphs 145:12     239:6 263:16         88:1 97:6 103:1,5     312:2 315:13          163:22 164:12
paraphrasing          268:11 271:22        103:7,11,13 104:4    patient's 93:11        169:13 173:13
 67:11                281:2 284:7 285:5    104:6 118:21         pattern 52:8 131:9     185:4,6 186:2
parent 83:20,20       286:6 288:12         129:21 139:20        patterns 249:19        188:3,14 189:5
 84:1 160:20,22       291:13 294:17        144:6,8 173:22       pay 63:19 64:12        190:17 193:7
parenthetically       308:18 319:15        178:1 181:17          71:17,18 91:18        194:2,3,6,12,18
 78:18               partial 127:1         194:7 222:18          141:17 189:21         195:20 196:21
Parenting 176:16     participating 17:3    230:8 231:1,3,5,8     321:16                197:17 198:6
parents 49:14        particular 21:2       231:9,11 232:22      paycheck 206:13        200:7 201:1,3,4
 160:16,18,18         48:1 57:15 102:5     236:18 237:15        payers 91:17 93:20     202:4,16,18
 191:14 214:21        108:18 184:6,9       253:10 264:7         paying 64:19 91:19     203:15,19,20
 259:15               216:15 265:8         266:20 276:13        payment 257:22         204:7 205:11
Parker 2:9 4:16,16    296:8                290:14                258:10                211:9 215:13


                                Neal R. Gross & Co., Inc.
                                       202-234-4433
                                                                                              Page 350

 216:10 217:12        perfect 224:7         322:5               phasing 11:16         pinkish 21:7
 218:15 219:1,2        277:19 278:14       pharmacist 5:1       PhD 2:3               pipeline 307:11
 221:12 225:18         280:2                53:6 93:22 103:6    phone 164:7           pirbuterol 40:13
 227:12 230:19        perform 265:3         150:1 155:12          183:11                128:5,10
 231:14 232:17        performed 55:17       180:7 185:7         phones 164:2          Pittsburgh's
 233:17 235:4,11       125:1 286:9          188:10,11 210:10    photic 14:3             218:20
 235:15,16 236:21     period 44:11 76:20    245:22 262:18       photographs           pity 264:3
 245:5,17 246:20       78:2 107:1,10        263:16 288:3          146:16,20 163:3,4   place 25:4 66:19
 247:18,19 248:16      234:20 261:13        297:3,4 300:2,3     phrase 296:1            108:13 174:18
 248:17 251:16,20     periods 35:19         308:10              physical 127:2          176:11,20,21
 252:22 253:5,19      persistent 36:8,13   pharmacists          physician 41:16         180:20 188:2
 254:22 257:5,20       36:16,21 37:5,12     103:21 155:18         50:1 52:22 54:7       209:15 216:13
 259:13,14,17          37:14,20 38:7        158:7,14 178:3        65:15 79:14 86:21     225:11 246:11
 261:12 263:2          53:21 62:4 79:16     181:22 212:1          87:13 90:10 117:8     249:11 269:16
 264:16 265:10,11      82:6 85:6 237:8      217:17,21 218:4       117:14,15,16          278:8 292:22
 265:13,16 268:7       308:5 311:21         246:7 263:6,9,11      185:7 229:8           306:17 309:20
 268:16 272:14         312:2,3              298:2 307:20          234:20 235:3,6      placebo 50:15 58:7
 273:10 274:8         person 81:22          308:12                257:6 259:19          58:19 59:9 60:1,7
 276:21 277:10         140:13 142:19       pharmacologist         266:20 268:4          95:6
 280:20,22 283:1,5     154:17 157:7         4:19 75:7             271:2 273:13        placed 54:6 119:15
 285:12,22 286:2,5     165:8,8 246:8       pharmacology           274:2 275:14,14     placement 172:3
 286:15 287:8,9        262:16 271:4         316:13                277:22 288:4        places 15:17
 289:12 292:13         282:13 291:1        pharmacy 30:22         315:8                 148:18 186:5
 293:14,19 294:18      320:7                53:4 66:14 84:2     physicians 43:2         219:1 309:18
 295:6,11,21 297:4    personal 31:3         88:9 157:17 175:5     53:2 58:16 66:9       311:5
 298:17 299:19         68:21 75:11          175:13 176:10         66:19 82:19 87:2    plan 3:8 9:18 116:8
 300:1 301:9,13        160:15 269:20        178:16 180:6          97:17 101:1 190:7     122:12 123:4
 302:4,12,14           307:7                188:22 218:6          199:21 217:8          134:9 196:3
 303:19 307:21        personally 87:1       263:12 296:21         228:6 229:5           205:17 214:18
 308:20 309:6          223:3                297:10,12,21          243:11,15 287:6       222:3 224:18
 311:3,11,20 312:2    persons 229:16        298:1 311:14          299:3                 290:15 291:9
 313:9,14 315:5,18    perspective 3:6       320:8,10,21         physician's 146:3       307:4 313:1
 316:7,8 318:11,15     9:12 75:3 109:17     321:15 322:10         263:19              plankton 14:3
 319:3,5 320:3         168:8 277:18        PharmD 2:8           pick 136:3 171:6      planning 16:6
 321:11               perspectives 205:8   phase 1:6 7:2 9:18     178:15 189:1        plans 119:22 201:8
people's 265:3        petition 74:3 76:4    288:14                224:17 232:4          251:3,8 287:21
 301:5                 76:10               phased 23:13,14        300:21                291:2,5 305:14
percent 44:20,22      Pharmaceutical        26:17 119:16        picked 65:1 177:20    plants 14:2 89:3,6
 45:3,5 51:21 78:6     222:7 297:16         120:10 254:15         178:12 305:11         89:14
 78:8 79:13,13,14     Pharmaceuticals       267:4               picture 12:2,22       play 100:21
 79:19,21 80:2,4,5     2:13 112:15,20      phase-out 8:18         13:2,5 315:7        plays 204:5
 82:4,5,7,9 85:8,10   pharmacies 66:10      10:1,6 11:9,18      pictures 13:1,7       plea 272:22
 85:18 139:19,21       68:10 88:22          20:21 23:7 166:13     132:5 146:17        please 10:20
 140:3,7,9,12          149:15 157:14        167:21 177:11         152:5                 183:11 239:1
 141:7,15 198:3,15     172:14 176:9         178:9 179:4 184:1   piece 161:3 283:13      279:7
 198:18 217:6          178:17 246:4         225:13 248:18       pill 104:2 265:4      plenty 95:6 304:10
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                                 Neal R. Gross & Co., Inc.
                                        202-234-4433
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plus 240:9,12,14        229:6 257:21         post 23:20 173:11     287:12               322:6
pluses 105:7            269:13 273:12,16      225:1               prednisolone 49:14   prescriptions 24:7
pneumonia 151:12        293:15               posted 77:20         prednisone 40:6       66:4 88:8 263:14
  151:12               poorly 69:4 75:19      171:18 193:20        49:14 50:2 63:9     present 2:1,7 34:4
pocket 64:3            popular 59:13         poster 176:9         preferably 212:3      75:9 81:17 83:3
podcast 177:16          172:20                187:14              preferred 64:10,12    83:17 87:10 88:4
  181:12               population 3:7        posters 185:22        129:21 208:8         91:6,18 183:5
podcasts 171:1          9:12 75:3 90:17       199:19 200:5        prepare 182:2         191:5 227:17
  289:8                 90:19 96:9 110:10     210:1 289:4          198:1                271:1
podium 10:18            123:8 133:7,13       post-MI 138:20       prepared 178:11      presentation 5:17
  222:1                 141:7,15,19 149:4    post-shelter 79:2    preparing 102:4       10:17 32:4 33:20
point 11:12 21:21       154:21 195:4,5       pot 309:5             123:12               75:1,6 149:2
  22:1 24:15 26:9       241:10 279:13        potassium 47:9,11    prescribe 53:3        165:20 179:13
  31:8 40:10,14        populations 148:11    potencies 43:19       236:20               192:20 223:22
  60:4 71:3 84:4        191:5 195:6          potency 43:6         prescribed 24:10      228:2 273:9
  106:3 107:14          259:11               potential 144:18      41:16 58:16 67:16    288:13 308:1
  116:11 175:2,3       portion 49:3,4         282:4 283:16         87:14 98:14         presentations 4:9
  204:2 209:13,14      pose 119:9 225:4       296:3                195:17 196:1,2       6:1 35:18 177:16
  209:14 219:13         225:15 304:22        potentially 40:22     208:5,6              181:13 320:5
  228:11 240:21         316:19                74:11 108:9,11      prescriber 262:17    presented 81:20
  241:13 244:8         position 25:10         120:14 128:7        prescribers 65:22     89:21 135:20
  249:12 266:7,22       99:10 217:18          234:5 278:9         prescribes 62:19      136:4 239:9
  268:3 270:18          221:8 223:4 261:2    poverty 76:19 77:2   prescribing 66:8      288:13,19 290:15
  277:4 281:14          299:5                 77:10 83:9 133:10    232:1 262:16         312:8
  289:17 290:6,14      positive 129:10        134:15 148:20       prescription 24:20   presenting 115:15
  291:4 292:11         possibilities 74:11    160:18 187:3         33:2 42:15 52:21     228:16
  293:3 294:21          260:21                292:3                53:5,15 55:20       President 193:4
  299:16 300:13        possibility 74:6      powder 68:17          57:1 63:5 64:3,8    presiding 1:11
  301:19                113:8 123:13          129:15,19 130:2      64:22 65:17 66:21   press 175:16
pointed 293:15          125:3 174:10          130:10 264:6,12      67:17,20 68:5        177:17,18,19
points 46:9 95:3        211:3 275:18         practically 29:17     75:22 84:3,10,22    pressure 127:1
  158:5 162:17         possible 48:3 122:5   practice 66:2,8       87:17 88:9 91:4     presumption 276:2
  227:8 295:16          129:15 143:10         71:1 109:2 147:11    91:16,17,19 92:6    pretty 19:3 22:11
  296:2                 159:9 208:19          161:10 204:13        92:7,16 93:18        23:8,12 24:6 47:3
poison 247:6            213:2 222:20          226:17 258:16,18     94:6 95:14 96:4      64:1 129:19
policies 14:15          226:19 240:18,19      311:14               98:19 100:3 101:8    147:21 159:12
  157:8 206:8           244:1 247:16         practices 88:4        102:1,7 105:19       181:21 215:3
policy 2:4 5:15 73:2    248:15 258:7         practitioner 54:7     108:5,6 115:1,3      241:14 269:5,6
  73:4 91:6 156:16      272:20 293:11         65:15 237:13         115:20 140:19        275:22 295:19
  157:2 206:9           304:5 319:18          271:3 277:13         147:20 156:18       prevalence 78:5,10
  271:16 307:8          321:2                practitioners         157:12 162:1         78:13 79:18
polished 317:22        possibly 40:18         151:10               178:16,18 180:8      147:22 215:1
poor 39:21 58:1         116:14 126:7         precautions 242:16    185:2,3 189:1       prevent 33:22
  61:18 76:18,21        176:16 177:1,8       precise 303:13        198:14 199:16        36:22 55:11
  77:11,12,17 79:7      182:9 185:5          predecessor 110:17    207:18 212:14        125:21
  79:21 84:7 194:13     255:14 275:20        predict 315:17        214:17 228:6        preventable 57:8
  196:19 214:10         291:9                predicted 44:21,22    277:22 309:12       preventative 53:19


                                  Neal R. Gross & Co., Inc.
                                         202-234-4433
                                                                                              Page 352

preventer 41:5       print 301:15          proceed 40:17         242:13,17 244:13     professional 35:14
preventing 34:13     printed 182:22        process 19:18 20:3    244:16 245:3          100:1,9 175:1
 37:4 281:4          printing 248:11,13     21:10 22:6,10,15     247:6,21 249:13       181:14 185:6,9
prevention 37:7       249:15                22:19 23:2 25:4      249:15,20 250:15      210:6,10 217:13
 39:7 100:11         prints 289:2           26:8 28:8 29:12      250:17 251:9          219:6 282:12
 176:19 239:4        prior 79:14 80:3,7     44:11 45:22 49:11    252:18 254:9,14      professionals 42:12
previous 51:19        81:6 82:9,10,11       54:15 68:6 73:10     261:9 271:18          47:15 170:14
 55:21 56:3,21        201:13                74:1,7 104:4         274:14 275:8,20       174:3,5 206:7
 119:5 198:18        prioritize 256:3       109:18 142:7         275:22 276:16         219:10 230:3
pre-printed 66:21    priority 83:19         197:11 260:20        279:4,14,19           289:5 307:20
pre-shelter 79:1      148:9 296:20          286:9,12             284:11 289:13        professions 99:8
price 120:15 122:5   private 117:15        processes 28:11       290:13,17 291:19     professor 94:13
pricing 121:11        250:17,19            produce 169:5         292:10,14 293:7      proficient 140:3,22
pride 119:17         Prize 15:15            200:4                296:9,14 297:6        141:4
primarily 6:1        PRN 53:3 66:1,4       produced 60:20        301:20 302:4,7,7     profit 193:6 206:5
 40:12 89:10 122:6   probability 140:7,9    199:20               306:3,7,11 309:7     profound 47:21
 236:11 251:10        140:12               producing 28:14       321:16                95:2
primary 8:17 46:18   probably 11:19         173:22              production 17:9       program 36:11
 100:10 118:2,7       23:6 41:1 51:22      product 7:4,6,16      121:13 305:22         37:7 62:2 65:2
 122:7 124:2          61:21 69:11 71:11     7:22 9:11 11:16      307:3                 69:15 125:11
 148:22 154:8         87:8 104:20 106:2     24:11,16 25:18,20   productions 306:14     170:10 178:12
 191:5 250:22         119:9 127:22          28:18 30:14 32:5    products 2:2,3 4:15    201:18,20 202:8
 251:4 252:21         131:4 132:10          32:17 44:1 57:12     5:5 15:20,20 16:6     214:3 218:21
 254:3 263:19         133:8,11,13,15,16     57:15 58:9 59:13     16:11 17:21 22:20     219:22 220:13
 299:2 309:6,9        134:2 135:7           61:4 64:6 71:22      23:19 24:2 25:3,7     239:4 263:8
 313:19 315:21        152:21 163:2,19       74:3 96:6,8 100:6    26:6,10,18,21         266:16 298:12
Primatene 41:11       168:10 175:4          100:18 103:12        27:2,13 30:1,3,4     programming
 41:13,19 42:21       185:4 188:12          109:17,19 112:16     31:10 32:7 33:7       220:8
 44:17 45:12 54:22    190:11 219:2          113:2,17,21 114:8    61:1 62:8 72:3       programs 199:17
 57:12 59:8 61:1      224:9 230:16          114:18 115:5,8,22    88:15,16,17,21        205:4,5,14 206:6
 62:17 64:18 65:13    244:22 250:16         116:19 117:2,7,12    91:3 100:22           215:4 218:11,13
 71:21 74:15 113:1    280:14 296:6,20       119:11 120:10,19     104:18 105:16         220:17
 113:9 194:21         302:2 304:15          121:2,22 122:1,6     106:5 116:10         progressive 52:10
 198:4 203:1          310:7 312:18          122:11,21 123:4      124:16 126:17         87:3
 207:14 209:2         313:17 314:3          124:1,7,16,17        133:9 150:9 152:6    project 81:2 184:15
 214:14 237:9         322:12                125:8 127:11,15      158:12 170:2,4       prominence 280:15
 245:21 250:18       problem 7:5 13:10      128:19,20 129:13     171:8 172:2 182:5    prominent 211:18
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 318:15               111:11 235:1          169:21 175:4,8,9     227:15 232:3         promote 122:22
prime 127:20          259:21 268:2,8        177:9 180:3 185:2    234:5 237:3 255:7     222:14
 217:18               283:5 297:13          185:3 188:9          268:19,21 271:17     promoting 109:1
principle 17:15      problems 96:4          190:20 203:6         271:17 285:13        promotion 122:14
 18:5,12 25:8,9       103:9 107:14          209:1,3 211:9        288:12,14,18         promptly 92:12
 88:3 98:9            124:21 258:9,10       228:5,5,6 229:15     290:20 303:7         propellant 312:11
principles 15:5       264:11 266:5          236:10,13 239:14     309:11 319:3         propelled 6:15 25:3
 26:14                279:9,11              240:5 241:19        profession 161:12      29:14 109:14


                                Neal R. Gross & Co., Inc.
                                       202-234-4433
                                                                                             Page 353

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protecting 22:11      160:9 166:3,6        purchasers 242:15       323:8               322:17,22
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Protection 2:13       172:4,5 177:1,13     purchases 131:5                Q            139:15 303:2
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protects 12:10,19     192:20 201:19        purchasing 164:12     qualified 23:17       289:1 298:8
Protocol 8:4 9:6      205:5,20 206:6,8      272:1,3              quality 115:15      quirk 105:22
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 222:9 261:4 303:5    271:11 289:2         pursuing 260:17         87:17,21 93:9     quite 38:16 47:14
Protocols 17:15       298:4 305:9          push 123:6 130:14       94:6 95:2 99:13     56:22 64:2 201:2
Protocol's 25:10      306:19 320:1          211:1 298:20           101:22 106:20       225:6 235:14
provide 8:3 9:11     publically 8:12       pushed 300:3            119:10,19 120:18    247:21 318:16
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provided 113:20       22:16 25:2 39:10      176:11 177:2           241:5 247:10
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provider 103:15       91:13                 197:7,14,19,21         259:7 265:6 266:9 radio 163:14 170:8
 160:8 161:21        publishing 117:10      207:14 208:15          268:12 269:11       174:19
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 284:14               98:20 107:22          253:16 263:1           305:1 306:15      raised 86:15


                                Neal R. Gross & Co., Inc.
                                       202-234-4433
                                                                                                  Page 354

raises 84:9 87:20       165:12 194:22          262:17 264:3          220:18 263:8         regarded 17:5
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ran 41:18 51:15       realities 143:8          269:2,16,21 270:3     296:8 301:3            99:16 194:21
  98:1 147:20         reality 82:3,13 87:9     270:17 271:7        recommendations          197:5 275:11
randomized 43:4         102:14 137:7,10        280:7,15 282:3        117:13 207:10        regardless 258:8
  58:20 59:22 95:6      138:5 143:3            283:15 285:16         211:13 258:4           258:16
randomly 50:14          145:16 146:14          292:9 300:5           308:13               regional 215:6
rapid 40:15 207:19      160:1 162:9            307:17 309:20       recommended              299:6
rapidly 48:14,15        164:17                 310:9,12,22           102:10 155:8         Register 193:21
rate 47:8,11 56:18    realize 103:3            311:10,11             278:18 280:20          223:5
  68:14 76:19 77:10     126:18 264:1         reason 31:16 51:7       294:3                regular 148:2
  82:1 86:10 125:17   realized 167:20          87:13 102:9 124:3   recommending             156:14 214:16
ratio 56:18 57:5      realizing 122:6          125:4 146:8           269:7 284:19,21        218:17 227:14
  269:13              really 17:14 19:13       185:12 210:7        record 112:10            231:20,21,21
rational 32:22          29:17,22 31:12,12      251:18 264:22         192:14 241:6,15        234:18 235:3
reach 156:13,15         31:16 33:20 43:17    reasonable 32:22        323:8                  280:20 281:12
  167:3 168:4,9         50:22 52:5 64:14       118:22              recurring 36:9         regularly 232:7
  169:12 170:11,15      70:7 75:8 78:14      reasonably 122:5      red 186:13 187:6,8     regulate 105:15
  182:19,22 185:4,5     79:6 81:16 84:16       303:13                233:4 252:17         regulated 15:3
  185:15 216:17         91:2,11 92:22        reasons 45:16           254:3,6                105:17 109:18
  220:22 285:9          94:9 97:9,9 123:2      60:21 91:21         reduce 17:8 116:18     regulation 15:1
  290:14,21,22          127:3,17 128:12        107:13 117:12         305:22                 17:20 30:5 32:8
  311:12                130:2,12,18,20         130:1 136:10        reduced 56:10            72:16 94:2 95:17
reached 18:9 216:8      131:4 138:5 140:5      140:13 156:6        reducing 7:20 16:9       105:22
  312:22                141:8,10 145:14        230:10 260:2        reduction 305:10       regulations 11:14
reaches 227:3           146:10,18 154:12       315:13              refer 158:20             11:15 14:15,18
reaching 15:10          157:22 158:15,16     reassured 297:5         243:19 271:16          15:2 17:14 72:2
  32:10 169:13          159:1 165:2,8,11     recall 29:6 41:8        275:16 284:13          72:13 93:17 100:8
  220:16                168:17 181:1           244:13,15           reference 163:21         101:20
reactive 270:21         184:1 185:14         receive 179:22          179:6                regulatory 2:4 5:14
  308:22                190:14 191:1,17        193:15              refill 66:22 75:22       5:14 22:6 99:21
read 27:11 43:1         192:3 194:17         received 74:2 82:5      84:2,10 87:17        Regus 50:6
  152:21,22 204:10      196:18 199:3           82:6 203:17           88:8,10 92:15        Reidenberg 2:10
  249:14 253:20         200:18 203:22        receives 67:15          93:19 102:1 153:6      4:18,19 9:9 70:22
  276:20,21 288:22      204:16 207:3         receiving 206:15        156:14,18 189:2        75:2,4 76:8,12,17
  288:22 294:15         208:3,7,21 210:7     receptor 48:6           322:8                  94:18,19,22 95:9
  308:12                211:11,20 212:12     recognize 99:2,3      refilled 52:21 93:13     95:18 96:13,16
readily 38:16           212:21 213:3,8,13      116:20 276:9,13     refills 53:3,4 65:22     97:1,14,19 98:6
ready 113:6 123:19      217:11 219:18,22     recognizing 243:15      66:18,20 199:6         101:11 102:21
  194:8 287:4           220:3,18 223:1,2       277:18                240:9,13,15            106:6,11,15
  317:22                224:4 228:9 230:7    recommend 49:8        reform 161:3,7           107:17 108:3
real 132:4 138:4        230:20 231:8,13        257:12 258:12       reformulation            111:15 123:10,11
  143:4,5,6 144:15      233:14 235:9,11        268:13 280:18,19      25:18 27:22            187:19,20 188:16
  146:10,14,19          235:12,16 236:3        300:3                 275:22                 225:17 236:6,7
  148:6 149:10          236:11 237:16        recommendation        refrigeration 15:19      243:4,5 259:2,3
  150:3 157:22          252:16 253:4,21        40:16 211:17,22     regard 279:11            269:9 273:3,4
  161:6 164:21          258:6 259:7 260:4      212:15 219:12         305:1                  299:9,12,13


                                  Neal R. Gross & Co., Inc.
                                         202-234-4433
                                                                                                Page 355

  311:17,18 313:7,8   relieving 34:11         185:3 209:1 264:4   resources 86:2        retrospect 123:13
  315:3,4 316:5         47:7 111:19           275:20 306:3          164:19 167:18       retrospective 55:16
  321:6,9             remain 124:1          replenished 13:14       168:12 169:18       return 69:3
Reidenberg's            211:19              report 37:8 39:12       182:21 299:1        reversal 47:19
  185:21              remains 231:7           41:14 141:8         respect 93:16         reverse 61:12
reimburse 71:16       remarkable 16:12      reported 85:19          101:22 102:5        reversible 43:11
reiterating 234:10    remedies 150:21         198:6                 259:20              review 124:9
related 24:16 66:18     151:4               Reporter 1:17         respected 75:8          231:20 239:19
  193:11 214:7,13     remember 35:3         reports 279:3         respiratory 52:12       273:9
  215:14 216:14         41:12 51:11 73:6      300:22                104:5 151:10,13     reviewed 39:9
  242:17 264:18         205:17 231:15       representative          151:15 222:12         79:12 116:9
  265:21 266:1          232:5,7 275:4         78:22 79:1,3,7        266:4 308:21        revised 37:8
  300:19                280:3               representing          respond 40:21         reworked 163:7
relates 186:10        remembers 107:1         112:19 196:5          45:12 51:6 60:13    re-enforcement
  187:11              remind 196:21           201:6                 60:15 126:6 236:4     69:17
relating 265:2        remnant 172:9         represents 242:5      respondents           re-evaluate 54:10
relation 55:21        removal 4:7 22:7      reproducibly            198:12              re-evaluating
relationship 34:9       23:15,18 25:2,6       264:13              response 16:3 34:9      73:11
  55:18 56:19 90:13     25:13 26:5,10       request 212:16          39:19,22 40:1,15    re-formulated
  257:6                 27:17 29:8 117:12   requested 20:17         42:20 43:12,16,21     128:1
relative 43:6 55:17     241:19 242:15       requesting 20:16        44:5 54:12 61:13    re-formulation
  62:16               remove 27:12          requests 172:15         61:18 222:9 223:4     126:10 127:14,20
relatively 27:1         60:22 122:3 279:4     220:2               responses 197:17        128:13 129:8
  43:12 108:15        removed 24:17         require 125:20          198:3                 130:6
relatives 79:5          26:22 28:15,18        207:21 212:1        responsibilities      re-formulations
release 26:1 28:2       30:14 61:3 198:11     274:15 309:12         17:8                  126:16
  29:5 177:17,18,19     250:18 303:8        required 22:14        responsibility        rheumatoid 100:9
  241:1               removing 18:14          127:10 274:19         90:11,14,17,18      rheumatologist
released 116:11         61:15               requirement 54:1        236:9,12,18,21,22     101:3
releases 25:20        Repair 200:11         requirements 8:4        237:2 260:6 292:8   rich 79:22
relegated 38:5        repeat 44:11          requires 32:8 54:20   responsible 82:20     right 32:20 113:9
relevant 11:11          202:11 276:6          61:16 83:18 92:9    responsive 34:12        136:7,17 140:2
  24:14 47:6 166:21     301:8 315:21          94:2                  45:9 49:20            142:18 145:2,18
  215:12 274:20       repeated 40:8         requiring 85:7        rest 19:12,21           150:21 151:3
relief 39:5 42:22       45:22 50:11           127:12                141:18 258:1          159:9 161:4,5
  52:17 56:12 63:11     243:10 301:18       rescue 202:17           264:5 301:22          164:5 169:14
  70:4,13 98:14       repeatedly 41:6         281:5               restrictive 233:18      170:1 176:7,11
  113:11,13 153:18      52:9 142:3 259:4    research 5:11 44:8    result 50:3 130:4       182:13 186:10
  209:21 261:19         301:15 306:10         92:14 166:4           317:19                188:8 193:18
  320:22              repeating 301:4         193:16 194:17       results 52:8 193:17     194:18 202:12
relieve 36:18 38:21     306:21                210:21,22 211:2,7     194:17                203:15,19,20
  38:22 40:6 51:13    repercussions         residential 59:16     resume 112:7            230:13 232:22
  60:18 61:5,20         207:1               residents 68:12         192:7                 234:6 249:11
  70:3                repetition 204:12       150:12              resumed 112:11          250:5 254:5
relieved 46:12 47:2   replaced 73:15,22     resource 171:16         192:15                256:22 258:22
reliever 207:19       replacement 24:11       175:14 177:21       retail 30:19            262:8 266:22
relieves 7:16 55:11     117:1 130:8,11        178:21 295:19       retrain 232:8           303:12 320:3,6


                                 Neal R. Gross & Co., Inc.
                                        202-234-4433
                                                                                               Page 356

rights 195:16,22        147:19             samples 118:9           246:18 271:20,21      21:7 37:2 44:18
right-hand 12:21      running 93:22          229:4                 291:11,12 298:13      46:4 47:1,10
rip 290:1               208:13 278:6       sampling 229:11         300:9,10 313:22       50:17 56:22 57:17
risen 109:22          runs 197:2           SANDER 319:8            314:1 316:3           66:15 77:6,11,17
risk 52:20 53:9       rural 195:4 244:6      321:11                317:17 320:4,14       78:1,3,10,12
  55:15,17 56:9,14    rushing 321:15       Sanders 192:21          320:18 321:7          80:16 90:12,20
  56:15 57:2,4        Ruth 2:9 4:16          286:14,22           school 4:17 75:15       117:8,13,16 132:5
  63:13 104:5 282:4     104:21 135:12      Sandler 193:1,3         140:8 191:10,12       147:13 150:2
risks 315:14            199:13 202:13        204:6 206:11          195:3,9,18 196:12     152:20 153:9,16
RiteAid 176:19          226:4 259:4 320:9  sat 104:22 142:14       219:21 220:11         154:2 156:4
road 128:7 157:16     Ruth's 236:8         satellite 322:6       schools 178:3           159:22 167:3
Rockville 1:11        Rx 96:8,11,12,22     satisfied 29:10         181:22 191:10         190:2 195:6 198:3
role 228:12,18,19       98:5 261:8,10        197:12                196:11 219:20         198:15 207:17,21
  283:16                                   satisfying 25:15        263:12 297:21         235:3,18 237:9,19
roll 304:2                      S          saturation 184:2      science 145:5           238:5 245:21
room 1:11 40:17       SABA 207:17          save 65:14              316:12                249:4 253:5,18
  45:8 50:3 51:4,17   SABAs 207:15         saving 62:6 195:17    scientific 16:13        254:1,22 257:5
  68:10 80:19 87:5    safe 61:14,15        saw 141:18 149:20       17:16 18:5,12         259:11,12 261:17
  116:2 142:18          100:20 103:7         233:6 245:3           39:10 66:14           267:10,17 268:4
  150:6 151:18          113:17 116:1         265:12                207:13                271:13 272:12,21
  183:3 190:7,12        133:6,13,16        saying 111:18         scientists 15:7         274:4 275:14
  200:14,14 203:13      222:14 242:16        145:12 174:13       scope 8:13              277:21 280:4
  210:20 220:5          297:6                190:12 258:20       scrambling 305:6        287:11 291:20,21
  278:7 303:10        safeguard 133:5        260:4 261:1         screen 224:21           295:6,17,22
  321:6,7             safely 33:4 103:11     264:17 265:17       screenings 218:12       300:20 305:11,14
rooms 190:16            104:7 145:15         267:22 294:6        seal 126:3              305:21 312:13
  191:3               safety 4:14 18:17      302:17 321:10       seats 192:17            313:2 314:2,3,4
Ross 2:13 11:3          110:1 173:21       says 7:21 28:13       second 13:19 23:16      314:21 317:5
  183:15                174:1 178:1          66:21 90:1 95:11      25:14,18 32:10,15   seeing 116:12
rough 118:18            181:17 220:9         153:11 155:4          38:11 92:8 95:13      245:11 273:20
roughly 113:13          279:4                188:10 252:18         120:11 121:7,8        303:19 309:14
  114:20              sake 27:5              278:18 295:14         124:22 126:11         322:21
roundtable 3:12       sale 30:7,8,15,17,18 scads 163:21            128:15 198:21       seek 257:16
  6:2 10:8 135:10       31:8,10,14 209:14 scale 14:8 216:12        211:22 234:17       seekers 194:4
  192:10 225:16         209:15 251:1,10    scanning 72:10          254:18 256:10       seeking 218:16
route 74:19             290:14             scattered 156:11        257:9 268:3           309:8
rule 22:16,18,18      sales 30:19 114:5    schedule 112:5,7        314:16              seen 41:1,16 65:7
  26:8 27:1,4,7,12      131:21 148:6         192:5               secondary 284:13        91:12 109:20
  27:15 28:9,10,12      198:21 199:5       scheduled 106:21      Secondly 48:11          147:12 191:12
  28:13 29:12 30:2      315:3,20             112:4                 315:11                235:16 279:10
  30:13 73:7 74:1     Sally 1:11 2:2 4:13 schematic 145:10       seconds 113:14          289:21
  93:21 128:9,11        6:9 189:10         schematics 146:18     secretions 38:14      Segal 32:3 185:19
  129:11 189:20       salmeterol 26:20     scheme 142:2            39:1 51:10            189:11
  241:18 276:1        salons 218:14          244:19 303:18       section 29:19         selected 273:11
  278:17              Salvation 186:13     Schmidt 2:11            255:21              selecting 44:6
rules 23:4              187:8                238:19,21 239:2,3   security 214:15       selective 57:20 59:1
run 65:14 97:13       sample 31:2 77:15      243:22 244:17,18    see 12:2,22 13:4        74:19 113:12


                                 Neal R. Gross & Co., Inc.
                                        202-234-4433
                                                                                                Page 357

  207:15 274:7          205:11 317:4          237:4 238:1,20      shipment 114:17       signals 110:1
self 68:1 100:18      served 23:22 191:5      239:8 240:1 242:3     130:22 307:10       signatories 17:1
  211:9               serves 122:6            242:20 243:21       shop 227:15 248:15    signed 221:18
self-diagnosable      service 86:2 170:8      244:17 250:3,14     shops 218:13          significant 25:21
  100:4,5,13            171:22 172:4,5        250:20 255:19       short 7:12 33:1         28:2 29:6 46:10
self-diagnosed          177:1 178:4 182:1     257:11 259:2          36:20 37:17,18        60:6,12
  200:21                289:3 301:19          260:9 264:14          39:3,16,20 40:5,8   significantly 57:19
self-diagnosis          315:9                 266:6 268:10          40:12,15,19 46:21     59:8
  273:14              services 1:1 195:7      271:20 273:2          47:5 49:8 50:12     similar 46:14
self-manage 161:20      214:1 300:14          274:11,22 280:5       50:16 51:18 52:7      116:13 119:14
self-managed          serving 123:9           283:18 286:6,16       61:17 90:4,5          241:16,21 307:13
  160:7               session 3:11 5:22       288:10 290:9          107:10 108:15       simple 126:19
self-management         10:8 112:3 192:8      291:11 292:6          113:14 157:11         128:14 140:20,21
  138:19                192:20 205:20         294:20 296:5          190:13 268:22         237:21 264:21
self-medicating         221:19 225:10         299:8,12 300:9,15     274:9 296:1           285:1 292:14
  277:14              set 77:4 245:17         302:1,22 303:22     shortly 247:22        simplicity 295:1
self-treat 90:9         248:15 255:14         307:14 308:15         248:1 305:19        simply 79:8 207:2
self-treated 200:21     303:15                311:17 312:17       shortness 7:17 35:1     243:19 311:21
self-treatment        sets 99:16              313:22 315:1          134:20 153:20,22    sing 149:11
  35:12 312:4         settings 68:10          317:1 322:11          270:12 272:5        single 142:19
sell 133:1,3 134:6    seven 56:4 78:7       shake 310:18            277:8                 152:14 199:11
  187:21 188:5          79:20               share 63:17 123:6     show 68:14 140:4      sit 164:17 220:10
  250:9               seventh 24:9            136:1 141:5           171:10 190:12         285:13 310:13
selling 114:4 188:6   severe 40:20 54:3       166:22 205:8          249:17 261:18       site 220:9 299:20
  240:5                 55:14 56:7 79:15      288:8 317:14,22       262:9               sites 158:20 220:16
sells 63:4 134:6        82:6,10 215:14      sharing 166:15        showed 15:9 82:14       242:13
send 103:14 132:6       216:19 235:21       sharp 192:8             83:14 91:1 98:22    sits 173:12
  174:8 177:4 182:2     281:10 282:7        sheet 171:21            107:22 111:16       sitting 4:11 72:2,17
  215:20              severity 230:1          291:14 294:14         128:9,11 181:20       151:4 152:4 153:6
sending 175:1         Seymour 1:11 2:2      sheets 170:14 289:5     182:15 188:17       situation 43:17
senior 220:14           4:3,13 5:16 10:15   shelf 151:4 152:5       216:2                 46:8 222:13
  291:8                 33:9 62:12 74:20      175:7 207:3         showing 13:3 21:1       264:19 278:8
sense 20:19 76:3        94:17 95:19           210:14 249:17         51:5 55:10 89:8     six 38:5 39:18
  123:7 163:3           102:19,22 106:19      253:18,19 255:8       95:7 111:2 185:13     53:20 78:6 81:6
  174:21,22 306:20      112:1,12,19           255:16 290:2        shown 60:20 82:2      size 221:9 290:1
sent 254:2              117:20 118:14         313:11 314:8,14       245:4 282:17        skills 137:13 139:1
sentence 257:1          119:7 122:9           321:1               shows 53:7 81:10        139:12,17,19,19
sentinel 108:18         123:10 124:11       shelf-talk 175:7        262:5                 141:4 147:8
separate 76:15          130:19 135:6        shelf-talkers         sick 97:11 283:6        164:13,16
  267:2,13 294:14       165:18 183:13         289:22              side 12:1,21 57:21    skin 13:20
separately 240:15       185:19 187:19       shelter 77:14,18        57:22 116:18        skipped 238:2
Sepercor 223:7          189:7,11,22           186:14                147:9 159:8         slated 212:18,19
September 1:8           191:22 192:16       shelters 75:17          252:21 269:14       sleep 46:12
  13:9                  205:19 221:17         78:17,19 79:6         310:11              slide 13:19 14:11
Serious 81:6            223:15 224:14,22      80:3 186:1          side-by-side 285:8      21:12 24:13 26:17
serum 47:9              226:1 228:21        shelves 155:18        sight 201:22            27:14 96:2 107:22
serve 8:20 193:7        230:5 234:7 236:5   shift 280:8           sign 212:11             150:4,7 203:5


                                 Neal R. Gross & Co., Inc.
                                        202-234-4433
                                                                                                Page 358

  279:15 282:17       somewhat 127:15         104:12 137:17         124:6               statements 221:20
  286:8                 231:7 254:21          205:2 206:3 222:4   stable 124:1 131:9      283:21,22
slides 14:12 22:22    soon 16:1 117:6         278:15              staging 271:10        states 1:1 22:7 57:7
  28:4 77:20 153:10     304:4               speaker 205:20        stakeholder 178:4       76:19 78:6 83:16
sliding 216:12        sooner 87:6           speakers 4:11 8:11      182:6 289:6           86:12 114:13,17
slightly 276:10       sorry 83:10 189:9       192:9 223:2 323:3   stakeholders            130:21 131:7,10
slip 140:10             189:12 238:22       speaking 9:5            170:15                131:14 132:5,7,15
slow 22:19              243:4 247:12          251:10              stand 321:15            148:15 177:8
slowing 20:20         sort 18:12 20:19      speaks 204:4          standard 19:3,4         189:13 195:15,21
small 64:1 118:8        25:1,8 65:4 67:11   special 63:1 65:6       137:1 140:20          196:5 224:10
  132:10 186:5          69:19 70:19         specialist 281:14       231:18                240:17 244:6
  191:13 302:13         108:12 122:20       specialists 217:14    standardized 220:4      251:1,6 259:8
smaller 61:21           134:10 135:2        specializes 69:14     standing 20:18        state-by-state
  176:18                137:4,14 226:13     specially 103:21        128:6                 95:15
smiling 256:19          234:2 235:9         specialty 231:18      standpoint 19:1       stating 119:11
smooth 38:10,21         238:11 245:1        specific 58:21          126:14 231:2,12     statins 104:20
  39:3 51:11,14         246:5 253:2 258:2     127:16 162:15         241:7 253:11        station 172:7
  115:10 222:19         266:5 267:8,19        166:8 207:10          270:2 276:12,13     statistically 46:10
  267:10,12             268:5 280:17          213:3 216:21          305:9 306:20        status 13:22 149:1
snapshot 139:16         282:9,10 284:14       229:1 230:14        standpoints 209:8     stay 58:3 151:16
social 170:22           292:16 293:5,12       236:14 253:7        stands 254:7            241:15
  214:15 291:18         293:15 301:1          268:14 284:19       start 4:9,12 9:1      step 8:21 53:20
  316:12                309:3 311:19          296:8                 50:2 111:17           125:17 144:5
society 18:18 93:2      313:4               specifically 11:15      150:16 162:20         165:3 207:4 230:1
  111:10 260:6        sorts 293:1             16:7 17:20 29:20      174:15 181:15         262:2,8
  263:10              sound 148:5,14          123:15 166:9          192:18 225:11       Stephen 2:12 9:14
socio 244:22            155:6                 167:8 179:2,19        249:22 257:5          112:14
socio-economic        sounded 147:1           187:14 194:21         300:1 301:9 307:8   steps 31:7 38:5
  292:4               soundingly 276:14       268:17              started 4:4 15:6,22     142:9 145:6
sold 74:15 85:14      sounds 136:17         specifics 242:11        16:8 21:11,19       steroid 38:1 45:17
  113:21 114:2          143:21 148:19,19    speculate 120:14        87:6 102:3 154:13     50:20 97:3 308:6
  118:20 147:2          240:3 245:12          127:17                155:11 195:14       steroidals 98:16
  159:11,14 188:1,9     256:4 261:11        speculating 75:20       238:22              steroids 45:15 62:4
  240:15 251:12,14      296:7                 82:15               starting 19:22          63:8 85:7 87:6
sole 11:18            source 164:3          speculation 189:2       44:15 249:12          90:5 91:21 103:14
solution 103:2          272:16 310:20       speculations 83:5     state 66:10,10          127:22 273:17
solve 103:9           South 114:14 196:7    speed 10:12             93:15 95:16           308:3 312:5
solved 98:11          so-called 88:22       spending 151:1          131:15 157:18       Steve 247:11
somebody 47:17        space 172:9 247:1       186:3 235:21          195:13 196:4,14     stick 252:17
  65:12 82:19 83:12     252:11                310:12                214:3 241:6         sticker 175:7
  98:7 108:1 157:11   spacer 266:2          spent 263:5 311:7       245:21 299:6        sticks 290:2 301:11
  183:16 229:5        spacing 301:18        spirometry 47:9       stated 22:9 259:19    stock 162:3 254:16
  235:18 240:6        Spanish 177:16        spoke 26:16             275:17 307:3        stop 20:6 233:4
  264:12 281:5,11       181:11 200:10       spread 114:21         statement 94:13       stopped 47:18
  282:16 289:19         251:5,10,11         sputum 58:8,9           119:15 196:15       store 54:22 62:18
  292:21 320:19       spasms 7:20           stab 159:10 160:11      241:15 293:6          114:11 115:21
someone's 252:20      speak 8:12 9:7        stability 116:19        295:3                 132:2 133:5


                                 Neal R. Gross & Co., Inc.
                                        202-234-4433
                                                                                                 Page 359

  143:20 149:8,10     studies 42:16 44:13   success 17:5 21:15       236:8                 264:4 302:5
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  150:13,15,17,20       55:10 68:8,11,14    successful 103:20      suppose 154:10          99:17
  152:4 156:16,16       78:16 80:10 82:14     172:9 184:4            193:17              switching 96:19
  158:13 242:4          116:4 125:1 262:2     200:15               supposedly 154:4      Switzerland 21:4
  244:9 245:20        study 43:7 44:3       successfully 24:17     sure 62:17 67:8       symptom 54:13
  255:8 270:16          45:7 50:13 51:15      65:13                  84:5 95:20 96:16    symptomatic 36:8
  310:1 314:7           52:18 53:7,11       suddenly 321:12          97:5,14 101:11,13     60:8
stores 30:22 63:1       55:16 56:17 58:13   suffering 193:10         102:21 106:22       symptoms 34:11,18
  63:19 114:10,10       58:18 79:10 80:15     204:15                 107:3 123:22          35:20,21 36:9,12
  122:13,13 132:20      81:6,11 84:20       sufficient 34:7 39:5     144:10 156:21         36:18 37:4,11,15
  143:21,22 156:21      85:5 99:1 111:16      93:12 229:10           160:9 161:18          38:19 49:6 55:11
  163:15 186:5          116:9 188:17          256:13 257:3           163:1,7 173:13        56:12 59:20,21
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  244:3 297:15        studying 58:3         sufficiently 40:19       184:21 187:9          70:3,13 79:15
  307:21 310:5        stuff 88:22 146:7     suggest 213:11           188:11 190:14,21      140:14 151:15
stories 41:4            146:21 150:10       suggested 273:9          197:3 201:2 203:8     153:18 154:4
story 107:7             152:13 186:10         316:16                 222:18 227:11,18      208:17 268:8
straight 234:12         286:5 294:5         suggesting 215:17        240:8 244:18          270:19 271:1,6
straits 186:3         stumbled 44:5           315:2                  253:12 258:1,6        272:11 277:7,12
strange 100:1,7       stumbling 241:21      suggestion 219:17        261:16,17 262:4,7     281:16 321:22
strategic 194:5       subject 89:8 166:8      224:1 239:16           268:16 274:21       synergistic 60:20
  204:18                168:21 173:4          290:7                  276:5 285:16        system 77:14 78:3
strategies 201:11       176:1,12,17 177:6   suggestions 243:4        294:12 304:16         80:8 81:18 83:17
strategy 36:14 90:2   subjects 42:18 45:4     256:8                  317:12 318:16         160:5 161:8 209:5
  119:22 122:22         166:19 167:2,5      suitable 121:5           320:2                 219:21,21 221:13
  311:9                 171:3               suitcase 278:2         surface 13:5            258:15
stratify 258:11       submit 78:21          summarize 284:5        surprising 55:5       systemic 40:5
stratosphere 12:4,7   subscribe 308:9       summarized             surprisingly 46:7       48:20 50:10 61:18
  12:18 13:17 15:11   subscribers 171:4       229:22               surrogate 245:1         63:13 125:2
stratospheric 15:9      174:9               summary 85:16          survey 71:7 84:20     Systems 263:10
straw 160:12          subsequent 14:11      summer 217:2             85:15 139:22
street 157:2            22:22               sun 12:10,19             197:14,19,20,21               T
strong 117:13         subsequently 15:13    sunset 306:8             197:22 201:4        table 3:1 141:6
stronger 210:13         228:3               supervised 88:2,6        319:1,6,9             142:17 213:1
struck 75:18          subsidiary 112:21       91:7,22 94:11        surveyed 51:16          238:19 250:9
struggling 205:3      substances 8:5        supervision 53:1         85:19 201:3,5       tables 39:14
student 75:13           13:13 14:15 15:3      92:21 93:12 108:8      217:1               tablet 63:10 98:14
  79:11,12 300:14       16:20 17:10,19      supervisor 320:16      suspect 84:13         tablets 34:15 57:13
  315:9               substantial 73:18     super-specific           89:12 107:12          58:2 59:7 61:1
students 42:18          127:10                244:2                  208:16 257:19         98:13 308:2
  45:18 58:2 66:15    substantially         supplies 229:10          313:13              take 17:8 45:11,12
  69:1 111:18           259:12              supply 23:20 49:14     swallow 64:1            57:9 58:2 62:20
  150:12 195:22       substituted 60:16       64:13 118:12         swallowed 49:2,4        69:20 70:14,19
  273:7,22 274:4        297:6               support 194:7          swirled 105:3           83:21 88:18 98:12
  275:6 300:7 315:7   substitutes 18:22       206:8 215:11,13      switch 74:9 104:18      98:20 101:5,6
student's 195:16      succeeded 23:5          215:15,16 219:15       199:9,14 260:18       103:4 105:6


                                 Neal R. Gross & Co., Inc.
                                        202-234-4433
                                                                                                 Page 360

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  128:17 132:13         98:8 99:6 110:4,6     68:20 92:9 184:3       286:19 290:20       therapeutic 3:5 9:9
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  143:17 144:16         150:17 154:13       techniques 68:9          302:9 303:17          269:13 284:19
  150:12 151:17         164:11 187:13,17    technology 87:4          304:15 314:12       therapy 35:10
  152:13 153:1          197:18 208:3,7      telephone 50:1           318:19,22             36:19 46:19 54:6
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  174:7 178:8           271:18 273:14,14      202:1,6 267:18         184:3                 94:12 259:1
  195:14 223:11         277:7 280:1           319:21               tertiary 284:15         269:17 281:17
  232:13 233:16         282:10 300:1        tell 7:8 32:16 71:14   test 58:3 144:16,17     282:12
  251:21 257:11         311:7                 89:16 99:10 101:1    tested 67:19,21       the-counter 7:2
  265:8,13,18 268:6   tangential 276:10       106:9,9 142:18         140:14 253:2          35:12 102:12
  269:12 276:15       taper 305:21            146:9 149:20         testing 124:6           107:3 108:17
  282:1,13 286:1,16   tapering 314:2,4        156:2,3 162:2        tests 220:4             110:10,20
  291:7 296:10        target 149:3 154:20     184:4 187:6,7        Teva 223:7            thing 12:9 15:6
  304:6 323:4           168:8 177:7 190:6     205:10 228:9         Teva's 63:18            20:12 21:19 72:9
taken 13:7 51:19        191:6 214:20          232:11 251:18        Texas 114:19            100:1,17,17
  51:21 62:8 108:8      266:8 292:2           268:7 274:2          text 118:8              101:18 113:4
  127:21 259:14         299:14,18 310:3       277:10               thank 6:8,10 10:10      120:11 126:17
  280:15 288:6          311:10 318:12       telling 185:8 203:5      10:15,20 33:7,9       128:15 136:17
  317:18                322:5                 232:10 286:8           33:19 62:9 67:4       139:5 142:11
takes 30:6 43:15      targeted 283:15       tells 199:4 309:15       74:22 75:4 94:16      143:19 144:20
  68:5 98:17 108:1      292:1 296:10        temporarily 7:16         94:17,22 95:19,21     152:1 154:11
  145:2 265:9           307:17 308:13       temporary 113:10         112:8,16,18           157:13 160:13
take-home 61:9        targeting 267:12        153:18                 120:16 129:13         162:6 172:19
talk 9:10,16,21       targets 127:20        tend 102:9 146:20        130:18 135:14         186:7 187:10
  10:3 17:22 22:6       214:19              tenderize 217:18         165:18 183:12,13      196:21 203:4
  23:3 26:15 67:5     Tashkin 58:13         Tennessee 114:18         192:12,22 193:1       207:21 219:19
  76:5 90:16 95:22    task 24:6 141:20      ten-fold 53:14           200:2 205:7,18,19     230:13 235:2
  102:4 112:16        taught 35:4 52:15     terbutaline 58:22        206:1,2,17 221:16     236:16 246:17
  123:12 135:12         55:8 68:18            59:10 73:16,22         221:17 222:21         252:12 266:3
  137:15 150:1        Taylor 41:9           term 115:18 116:19       223:14,15,21          268:6 274:20
  156:3 166:5,9       teach 69:1,16 71:4      124:2 207:22           224:13,14 242:2       281:9,14 282:9
  176:13 183:10         150:14 220:3        terminology 7:15         243:21 288:10         284:10 285:6
  185:21 187:7          232:16 263:6          202:15 203:3           303:21 312:17         287:14 289:15,22
  188:10 204:6          264:7,11 265:7        278:22 279:1           322:22 323:2,6        292:11 293:21
  213:19 238:7        teachable 204:6       terms 63:11 67:22      thankful 203:17         294:16 304:12
  255:21 285:15         209:11,12 308:19      70:11 96:5,5           205:1                 310:9 319:12
  301:13 310:13       teaching 307:19         100:8 107:4          thanks 119:20           320:17
talked 29:1 71:21       308:8                 108:13 164:18          131:19 165:17       things 29:3 68:22
  82:21 133:20        teach-back 231:22       167:18 169:9           239:8                 102:11 104:3,9
  179:1 201:12        team 142:2              171:7 172:13         theme 261:20            117:22 121:19
  209:14 273:7        technical 25:17         174:11 226:12        theophylline 59:12      127:6 132:16
talking 12:17 15:21     27:21                 237:16 260:19          59:14 60:2,3,19       134:21 135:15
  18:14 28:4 32:1     technically 18:21       264:16 267:9           60:22                 138:2 139:12


                                 Neal R. Gross & Co., Inc.
                                        202-234-4433
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  174:12 181:6,16     187:12 188:8          299:3,13 302:14       226:10 261:21       times 14:21 35:1
  202:12 209:18       189:7 190:1,10,13     302:20 303:12,18      264:9 286:8 301:8     49:21 52:1,2 53:2
  213:15,21 216:22    191:22 193:11,17      304:10 305:4,8      thresholds 76:22        56:4 104:15
  217:3 220:2 229:2   199:2 200:22          307:18,22 308:7     threw 162:16            115:19 120:12
  230:1 231:8,10      202:13,18 203:15      309:17 310:10,22    throat 116:17           145:3 155:16
  232:8 249:9 256:1   206:18,22 208:2       311:6,9,18 312:9    throw 211:3 251:20      160:20 167:9
  259:4 260:22        209:3 210:4,18        312:17 313:3          251:22 292:8          249:10 289:16
  261:6 265:11        212:12 217:21         317:3 320:10,11     thrown 317:6            301:7
  266:18 278:11       220:15 221:1          322:11 323:3        thyroxine 93:7        timing 299:10
  291:21 292:20       222:22 223:13       thinking 82:19        tie 187:5               301:16 304:2
  293:1 304:14        224:15 225:8,10       102:3 134:12        tier 64:10            tiny 26:2
  308:9 309:16        225:18 226:6,8,22     145:22 151:21       tightening 277:8      today 4:6,10 5:21
  311:13              227:7 228:1,8,12      176:7 182:9,10      tightly 240:22          6:10 8:1 9:4
think 4:4 6:11 24:6   228:18 229:2,3,13     205:15 209:18,19    tightness 7:17          15:21 16:22 27:16
  33:10,16 47:18,20   229:13,18,18          209:20 223:2          34:20 134:20          76:10 110:5
  64:2 67:2,20        230:6,11,22           291:14                153:19,20,21          137:10 183:5
  69:13 74:20 76:13   231:11 234:7,21     thins 58:8              270:11                193:2,15 201:6
  81:16 89:15 90:6    235:8 236:5,11,20   third 25:20 26:1      time 6:5 14:16 15:7     206:12 210:19
  91:8,10,14,20,22    236:21 237:6,8,18     37:9 91:17 92:10      15:9,16,22 16:8       254:2 279:6,8
  92:2,5,8,10,12,14   238:1,3,8,10          93:20 103:3           19:10 24:8 27:2       291:7 323:1
  95:2,22 97:17       239:15 242:21         104:10 105:5          37:9 43:9 44:11     told 43:2 74:15
  98:15 99:6 100:13   243:13 244:4          187:1,1,2,2 189:1     46:9 55:11 59:14      77:19 94:14 101:5
  101:14,18,21        245:4 247:5,10        212:12,15 256:11      60:10 62:11 64:16     154:11 277:21
  102:15,19 103:2,8   248:21 249:9          257:9,20 258:2        69:4 76:20 77:18      278:5 313:15
  103:20 104:3        250:14 252:13         267:3                 78:2 87:10 97:13    ton 21:12,20
  105:2,22 106:7,19   253:10,21 255:12    thirdly 38:13 48:14     99:20 101:7         tone 138:12
  107:19 108:20       255:19,22 256:20    Thirty-three 217:6      105:13 107:2,11     tons 21:19
  109:16 112:1        257:14,18 258:3     Thoracic 111:10         113:6,21 116:11     tools 10:4 215:20
  126:17 128:2        258:17 259:3        thought 72:9 75:5       120:4 123:11,19     top 21:6 43:15,20
  130:13,22 131:1     260:6,11 264:20       76:2,7 84:8 96:18     128:20 135:15         114:17 131:7,9
  132:15 134:1        265:6,22 266:6,8      126:21 219:18         140:18 151:2          151:11 162:13
  135:6 136:5,11,14   267:5,17 268:5,10     245:10 246:18         165:17 171:16         166:20 181:7
  136:15 137:6,20     269:1 270:3,9,12      263:21 314:5          186:3 191:20          252:4
  137:22 138:9,16     270:13,17,18        thoughts 136:2          192:6 193:12        topic 80:1 105:12
  139:11 143:2        271:10,22 274:6       305:15                195:19 208:9,14       135:17
  144:14,21 151:14    274:20 275:7        thousands 171:4         209:2 220:19        topics 322:13
  152:10,15 153:12    276:11,21 277:3,5   threatening 36:6        222:17 232:3        tossed 256:1
  153:21 155:15       278:10,12 279:7,8     198:16,18 282:4       240:21 246:20       total 198:15 240:16
  157:10 158:6,7,8    279:17,22 280:6     three 16:15 25:15       251:2 260:18        totally 143:9
  159:14 160:5,8,13   283:10,18,20          28:3 29:2,9 37:13     266:19 271:16         253:14 293:17
  160:18 161:6,9,10   284:2,4 285:2         38:9,20 48:3          278:19 296:6,15     touch 311:3,4
  161:13 164:6,7      286:7,16 287:7,13     49:21 54:9 89:5       301:21 304:11,12      312:18
  165:5 167:14        288:11 292:9,15       101:6 114:7,20        305:5,22 313:5      touched 225:10
  169:20 176:13,15    293:16,18,22          118:19 124:12         316:16,17 318:5,8   touching 227:8


                               Neal R. Gross & Co., Inc.
                                      202-234-4433
                                                                                              Page 362

tough 209:6             50:11 53:12 60:9      156:13 158:18         118:18,21 120:1,5  163:2 196:7 204:9
town 63:19              71:8 86:21 87:1       171:17 190:21         140:13 152:9       220:6 221:5
toxic 42:8,14           87:12 103:11,12       209:4 214:4           155:17 157:9       226:12 231:15
  102:11                280:10                215:22 216:13,21      199:19 200:5       240:8,11 241:4
toxicity 60:20        treaties 17:6           218:3,6 220:16        201:17 206:13      246:2 262:10
traceability 244:12   treating 36:14          231:14 232:20,21      230:10 234:14      265:3 274:13
track 182:13            49:10 91:4 236:2      233:13 238:10         260:22 267:13      280:4 285:17
  258:22                258:19 277:15         253:8 256:2 268:7     273:8 275:11       286:5
traction 216:14         309:11                283:19 296:9          282:15,22 293:8   understandable
trade 72:6 175:15     treatment 6:22          304:2 305:4 309:6     297:17 314:10,11   159:5
trademark 120:22        32:20 35:12 38:6      319:10              type 35:14 62:18    understanding
  121:4,7 250:18        38:7 39:11,15       trying 14:8 31:17       67:14 163:17       30:12 105:6
traffic 233:8           59:16 84:11 87:21     62:2 70:2 80:12       194:20 208:5,6     132:12 134:9
trained 66:14           88:2,5,6 90:1,10      136:6 142:6           254:4 256:12       165:13,16 233:10
  103:22 104:1          91:6,8,22 92:1        153:12 155:9          257:2 322:10       270:1 281:7
  124:20 265:7          94:10,11 137:2        157:10,21 164:14    types 34:4 37:13     285:10
training 47:16          191:21 199:8          208:7,14,15 209:7     238:13 256:13     understands 165:9
  203:9 216:21          271:5,6 273:5         213:16 219:15         288:16 310:5      understood 169:22
  217:4,7,9,19          274:1 275:15          220:3 221:10,12     typical 12:12 67:15  227:3
  218:21                276:15 278:9          232:11,13 240:10      127:4 166:18      undertaken 183:21
trains 170:18           283:8 284:17          241:19 242:12         172:1             under-estimating
transit 170:17          304:17                244:21 256:20       typically 41:4 52:8  218:1
  289:7 291:21        treatments 31:22        263:6 264:17                            under-served 3:7
transition 20:4         39:17 117:9,17        272:18 285:9                 U           9:12 63:17 75:3
  22:4 31:20 32:19      275:12                294:4 311:12        ultimate 31:8       under-used 85:10
  33:4 115:11,11      tremendous 183:2        314:16 317:15       ultimately 16:20    unequivocally
  119:22 123:4        triage 103:6          turbuhler 264:8         19:5 279:12        236:17
  184:12 185:9        trial 43:5            turn 6:6 143:17       ultraviolet-B 12:10 unfortunately
  194:20 199:12       trials 58:7 95:7        196:5 299:1         umbrella 17:16       97:12 132:17
  201:13,14,15,17     triamcinolone         turned 263:18           186:13 187:10      133:4 135:4
  201:22 202:2,4,9      27:10               turning 196:8         unavailable 25:19    140:22
  203:11 206:19,21    trickle 208:13          287:10 305:13         29:4              uninsured 196:19
  211:9 217:2 218:5   trickling 267:20      TV 172:7 174:19       unaware 123:12      unique 185:14
  221:11 222:15,19    tricky 175:3 209:15     187:15              uncommon 37:21       222:13 266:5
  229:14 287:5        tried 193:19 318:4    Twelve 141:15         underlying 37:1      290:12 313:4
  305:5,16 306:7        319:8               twice 29:1 36:11        38:8 268:8        unit 53:12
  319:21              triggered 279:3         37:19               underneath 175:8    United 1:1 22:7
transitions 183:18    trips 149:19          two 6:20 7:4 14:20      181:8              57:7 76:19 78:6
translated 21:1       trouble 70:6 94:15      15:1,7,14 17:14     understand 38:16     83:15 86:11
translates 31:13        159:21 160:3          21:6,16 28:17         64:16 97:19 107:8  132:14 240:17
translation 210:3       246:2 252:7           30:11 35:17 39:17     122:15 126:18      251:1,6 259:8
travel 278:1            257:21                39:18 43:22 44:15     128:15 129:7      units 86:8,11
traveling 321:19      troubling 320:19        46:2,9 53:15,20       131:3 137:13       113:22 114:2
treat 59:20 86:19     true 62:22 92:5         54:14 59:7 66:22      138:13 139:6       118:20 244:11
  104:7 162:1 257:6   trusted 310:21          71:6 76:15 80:14      141:13 142:20     universities 300:12
  281:20 283:7        try 95:11 112:6         86:22 89:3 98:12      144:2 145:8       University 2:8,9,12
treated 37:22 47:10     132:13 137:20         107:11 114:7,20       160:14 161:19      4:17 5:2 15:8


                                 Neal R. Gross & Co., Inc.
                                        202-234-4433
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unprecedented         203:8 217:5            248:16 251:21       versus 37:11 60:7   270:15
 210:16               227:16 228:5         utility 302:15          80:15            walks 193:8
unresponsive 49:7     230:9,16,17          UV-B 12:19            viable 260:14 261:9Wal-Mart 62:18,20
 51:6,8               231:15 232:6,17      U.N 17:4              video 171:1 174:8   63:1,4 64:22 65:7
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 86:14 100:22         190:8 198:17           64:8                vulnerable 209:13   271:12 274:12
 101:2 108:7,7        210:17 227:5,6,12    varying 45:16                             275:1,9,16 279:16
 110:11 111:3         239:13 257:20        vasoconstrictor                W          280:3 283:6 285:6
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 178:13 195:17        156:13 169:1         version 115:12,13      66:6 115:21 142:9  179:5 197:9


                                Neal R. Gross & Co., Inc.
                                       202-234-4433
                                                                                        Page 364

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                               Neal R. Gross & Co., Inc.
                                      202-234-4433
                                                                                               Page 365

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worst 13:7             28:17 35:4 41:8     $200 64:7                                     306:4 314:6
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write 65:22 66:20      197:6 202:10        $60 64:5                                      108:1 255:18
                                           $80 202:4             1978 16:2
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 306:5                 224:12 239:18       $9.95 62:21 63:4                              59:6 85:5 113:22
                                                                 1990 62:3


                                Neal R. Gross & Co., Inc.
                                       202-234-4433
                                                                  Page 366

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610(e) 29:19
63 80:5


                                      Neal R. Gross & Co., Inc.
                                             202-234-4433

				
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