Review of Standard for Evaluating the Effectiveness of Contact

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					TECHNOLOGY/APPLICATION

Review of Standard for Evaluating the Effectiveness of Contact Lens
Disinfectants
Ruth A. Rosenthal*, Scott V. W. Sutton, Barry A. Schlech

Alcon Research, Ltd., Fort Worth, Texas

ABSTRACT: A new standard has been developed by the International Organization for Standardization (ISO)
for evaluating contact lens disinfectants. This paper reviews the ISO 14729 standard and applies it to
marketed products. The historical significance, justifications, scope, interpretations, application, and worthi-
ness are discussed. The standard provides a more consistent procedure and a higher standard for contact lens
disinfectants. As a result, more effective contact lens disinfectants have been marketed.

Keywords: contact lens, disinfectants, antimicrobial, ISO, method, procedure, standards

Introduction                                                        disinfectant and accessory products (e.g., cleaners,
                                                                    rinsing solutions) when tested by the Microbial
The international regulatory hurdles for approval                   Challenge Multi-Item Test (MCMIT) (44). On the
of a new contact lens care product were formidable                  other hand, the French guidelines (15,16,17)
in the 1980s and early 1990s. National bodies were                  required that a CL disinfectant show > 5 log reduc-
requiring specific, national tests to be conducted.                 tion on contaminated lenses without the help of a
These requirements were in response to concerns                     cleaning (rubbing) and rinsing step (similar to hard
over the contamination of lens care products spurred                surface disinfectants). The British (26) had differ-
by reports documenting contamination of lenses                      ent standards, requiring that a CL disinfectant meet
during consumer use (20,30,31,47,54), lens cases                    their preservative effectiveness standards (i.e.,
(6,11,19,24,27), and solutions (3,5,9,12).                          a 2-log reduction at 6 hours and a 3-log reduction
                                                                    at 24 hours for bacteria, and a 2-log reduction of
Several countries had specific sets of standards                    fungi by 7 days). The Dutch (13) had yet another
or guidelines which a contact lens disinfecting                     standard, mandating a 3-log reduction of bacteria
product (CL disinfectant) had to meet in order for                  within the use period and a 2-log reduction of the
the governing regulatory body to grant approval to                  fungi at 7 days (Tables 1 and 2). This diversity of
market in their country. The Food and Drug Admin-                   national standards meant that products had to
istration (FDA) guidelines were the most extensive                  be tested by multiple tests that were frequently
regulations governing the approval of contact lens                  ill defined.
disinfectants at that time (49,50) and they had a
significant impact on the development of the new                    Why Was the ISO Standard Developed?
international standard. The FDA required that a
CL disinfectant be tested by a D-Value test and                     Microbiology methods for testing CL disinfectants
D-Values be calculated (42), although no specific                   needed to be harmonized for three reasons. First,
criteria were set (43). A D-Value is the calculated                 a c c u r at e e s t i m a t i o n o f a n t i m i c r o b i a l e ffi c a cy
time required to reduce a population of microor-                    required precisely controlled and reproducible
ganisms by 90% or one-log 10 (log). In addition, the                conditions. The different conditions mandated in
F DA r e q u i r e d n o s u r v ivo r s a f t e r a l e n s wa s   different tests may have affected the apparent effi-
treated according to label instructions with the CL                 cacy of the CL disinfectants. Secondly, the expense
                                                                    associated with the multiple testing requirements
                                                                    h a m p e r e d t h e i n t r o d u c t i o n o f n ew p r o d u c t s .
* Author to whom correspondence should be addressed:
                                                                    Agreement was needed as to how to establish effi-
Alcon Research, Ltd., 6201 S. Free Way, Fort Worth,
                                                                    cacy criteria for these products. The third reason is
TX 76134. E-mail: ruth.rosenthal@alconlabs.com
                                                                    the consideration that contact lenses are inserted
Vol. 56, No. 1, January/February 2002                                                                                                        37
Table 1. Historical review of antimicrobial activity standards for contact lens disinfection solutions.




Table 2. Historical review of lens challenge testing criteria.




onto the ocular surface; therefore, a disinfecting       Developing the Standard
solution can not be required to be so strong as to
damage the patient’s eye.                                In the 1980s re pr esentatives from several CL
                                                         disinfectant manufacturers began to draft potential
This harmonization effort fell under the ISO um-         standards and criteria. A group of microbiologists
brella. The United States provided major support         from several of the companies in the United States
in the development these standards. The ISO 14729        worked together to provide procedural details
procedure, “Microbiological Requirements and Test        w h i c h w o u l d g ive c o n s i s t e n t r e s u l t s . T h e
Methods for Products and Regimens for Hygienic           recommendations were taken to the ISO committee
Management of Contact Lenses,” for testing of CL         (22) and regulatory bodies of the world. Comments
disinfectants emerged.                                   from the groups were incorporated into the

38                                                       PDA Journal of Pharmaceutical Science and Technology
standards. This was the basis for the current ISO                             Testing CL disinfectants for virucidal activity was
14729 standards.                                                              not included in the ISO 14729. The procedure is
                                                                              for testing CL disinfectants for individual use.
Justifications                                                                Viruses are obligate intracellular parasites and do
                                                                              not replicate or proliferate on contact lenses (34).
There were several areas of debate about the                                  Testing products with viruses is impor tant in
p r o c e d u r e b a s e d o n d i ff e r e n c e s i n h i s t o ri c a l   relation to trial lens procedures. Trial lenses are
perspective and usage. The United States FDA                                  reused between multiple patients, following proper
wanted organic soil to be included in the testing of                          disinfection. However, spread of HIV, hepatitis, and
CL disinfecting procedures. The United Kingdom                                adenovirus between patients is a concern (8,10,52).
M e d i c i n e s C o n t r o l a g e n cy ( 2 6 ) t h o u g h t t h a t
Acanthamoeba should be included. The inclusion                                Scope of the ISO 14729 Standard
of virucidal testing was included in the older
FDA disinfection procedures but was less of a                                 The ISO 14729 disinfection procedure evaluates
concern. These topics were annexed as informative                             the relative efficacy of the CL disinfection system.
technical reports into the resulting ISO 14729                                Two basic principles have been accepted. The first
procedure as described below.                                                 was that the new procedure would be based on
                                                                              establishing criteria that are realistic to achieve, with
A laboratory prepared organic soil composed of a                              the understanding that the innate antimicrob i a l
mixture of killed Saccharomyces cerevisiae and
inactivated fetal bovine serum was part of the                                Figure 1. Flow Chart for Stand Alone and Regimen
earlier FDA guidelines (49,50). This procedure                                Tests. This chart diagrams the relationship between
recommended testing lenses coated with microor-                               the Stand Alone Test and the Regimen Test in the
ganisms in this organic soil mixtures by the label                            evaluation of a new contact lens disinfectant. A
directions for use of the CL disinfection regimen                             summary of the criteria is provided in Table 4.
(7,28). Several representatives argued that testing
efficacy of the CL disinfectant solution in the pres-
                                                                                  Stand Alone
ence of organic soil provided useful information                                      Test
about whether the product may become neutralized
by organic material that is likely to be present on
contact lenses removed from the eye. The counter
argument was that the use of organic soil was not
                                                                                                 No                    No
useful because there was not a consistent method                                   Primary              Secondary           Test Failed
for preparing soil and none of the laboratory                                     Criteria Met          Criteria Met
prepared soils accurately modeled tear components
(2,18). Additionally, even tears themselves varied
                                                                                         Yes                     Yes
in composition from person to person (18,51,53). Fi-
nally, since the rubbing and rinsing steps removed soil,
it was probably of little value in the Regimen Test. As                            Stand Alone           Regimen
                                                                                   Test Passed             Test
a compromise, the use of organic soil in the Regimen
Test is an option in an informative technical report in
an Annex of the procedure. The practical outcome of
this compromise is that the use of soil is required in
the United States, but is not required in Europe.                                                                      No
                                                                                                         Regimen            Test Failed
                                                                                                        Criteria Met
Concern about Acanthamoeba infections in the U.K.
p r o m p t e d t h e d e b a t e o ve r t h e i n c l u s i o n o f a
                                                                                                                 Yes
requirement to Acanthamoeba activity. However,
the incidence of Acanthamoeba is very low (29,41)
                                                                                                         Regimen
and there are no standardized methods for testing                                                       Test Passed
Acanthamoeba (4). Therefore, this protozoan is not
required as a challenge organism.

Vol. 56, No. 1, January/February 2002                                                                                                 39
Table 3. Summary of performance requirements for ISO 14729 contact lens disinfection procedures. Passage
of the Stand Alone criteria allows the disinfecting solution to be marketed as a disinfectant. This requires
reduction of the challenge organism by the stated log unit values at the end of the disinfection period. Less
potent disinfectants may be tested as part of a regimen if they meet the “Regimen qualification” criteria
outlined.




activity of the disinfectant would be assisted by the     The secondary criteria required that the concentration
contact lens rubbing and rinsing regimen (23).            of each bacterial species be reduced by a minimum
Secondly, the new procedure would allow for               1.0 log unit, and that the sum of the log reductions
approval of a CL disinfectant based on its activity       of the three challenge bacteria had to exceed
within the lens care regimen.                             5.0 log units for the disinfectant to be eligible for
                                                          evaluation by the Regimen Test. This was believed
The final procedure consists of two parts (Figure         to be the minimal level of activity acceptable for a
1). The first part evaluates the innate antimicrobial     CL disinfectant, even allowing for the mechanical
activity of the disinfecting solution alone (hence,       cleansing of the lens.
it was named the “Stand Alone Test”). If a product
meets the primary criteria, it is exempted from           The ISO disinfection test has several roots. The
further testing by the Regimen Test. It is assumed        Stand Alone Test is based on pre-existing antimi-
that when used with the rubbing and rinsing steps         crobial activity tests. These procedures include the
(which removes 10 3 to 10 4 microorganisms from           FDA D-Value Test, the British Pharmacopoeia Test
the lens), the disinfectant will be capable of pass-      for Preservative Efficacy, and the Dutch disinfec-
ing a more stringent regimen criteria (21,39,40).         tion test (Table 1). The primary criteria of the Stand
The second part (if required) is the Regimen Test.        Alone Test are intended for CL disinfection prod-
The Regimen Test evaluates the antimicrobial              ucts with a higher level of antimicrobial activity. If
efficacy of the entire regimen described in the pack-     the CL disinfectant meets the primary criteria, then
age insert (e.g., rubbing, rinsing, and disinfecting)     testing by the Regimen Test is not required. The
(Table 3).                                                assumption is made that the rubbing and rinsing

40                                                        PDA Journal of Pharmaceutical Science and Technology
                                        Table 4. Summary of ISO 14729 procedure. ISO/FDIA 14729. Microbiological Requirements and Test Methods
                                        for Products and Regimens for Hygienic Management of Contact Lenses.




Vol. 56, No. 1, January/February 2002
41
steps of a regimen can be relied upon to lower the                          400% of the disinfection time for yeast and mold.
c o n t a c t l e n s b i o bu rd e n t o l eve l s s u ffi c i e n t t o   The additional sample time was included to pro-
e n s u r e e ffi c a cy w h e n u s e d a c c o r d i n g t o l a b e l    vide assurance on the reliability of the study. If
instructions. Therefore, further testing of that prod-                      the disinfectant meets the requirements of the Stand
uct would not be necessary when it is to be used in                         Alone Test, the product can be labeled as a CL
a standard lens care regimen that includes rubbing                          disinfectant.
and rinsing of the lens. The primary criteria of the
Stand Alone Test and Regimen Test criteria were                             The Stand Alone Test is designed to increase the
readily agreed upon. However, some other products                           stringency and the reproducibility of the test with-
marketed at that time showed weaker antimicrobial                           out sacrificing the disinfecting capability of the lens
activity. Therefore, the group agreed to add second-                        care regimen. Several changes were made in the
a r y c r i t e r i a t o t h e S t a n d A l o n e Te s t a s a            base FDA document with these goals in mind:
qualification for the Regimen Test. Addition of the
secondary criteria allowed weaker CL disinfection                           1.      Choice of challenge microorganisms
systems to be marketed as part of a regimen. These
products had proven safe and effective over time.                                   The Stand Alone test is conducted with a
In addition, the secondary criteria were designed                                   specific set of microorganisms chosen as
to prevent products, such as unpreserved saline                                     index organisms similar in scope to those
solutions, from being marketed as the disinfecting                                  of the previously used regulatory tests. The
part of a regimen. Therefore, if the disinfectant                                   most significant change is the use of the
alone exhibits a lower level of activity, then the                                  fungus Fusarium solani to replace the spoil-
entire r egimen is tested to ensure efficacy. A                                     age organism Aspergillus fumigatus in the
two-part or two-tier approach is not unique. The                                    battery of challenge organisms. This change
criteria of European Pharmacopoeia preservation                                     was justified on two counts. First, the fun-
efficacy test uses two levels of preservative activ-                                gus Fusarium is an ocular pathogen (25).
ity (14). The Regimen Test is based on the FDA                                      Second, an index organism should display
MCMIT and the French AFNOR lens challenge test                                      an intermediate spectrum of susceptibility
(Table 2). The Regimen Test evaluates the effect of                                 to disinfecting agents, allowing differentia-
the entire regimen, including the rubbing, rinsing,                                 tion among solutions. Fusarium solani is
and disinfection steps as a unit. The ISO 14729                                     clearly preferable to Aspergillus in this re-
Regimen Test uses the best of two procedures: The                                   gard. Finally, efficacy against Aspergillus
FDA MCMIT which evaluates the effect of the                                         is demonstrated in the test for preservation
disinfection process to eradicate microorganisms                                    efficacy, also required for regulatory ap-
and the French AFNOR Test which uses membrane                                       proval of a new disinfecting solution. An-
filtration for recovery and has criteria of a greater                               other important change was the control of
than a 5-log reduction.                                                             organism growth conditions. The ISO 14729
                                                                                    procedure has specific requirements for the
The Stand Alone Test                                                                number of passes from the original stock
                                                                                    culture and specific growth media, tempera-
The Stand Alone Test evaluates the innate anti-                                     ture and incubation times.
microbial activity of the CL disinfectant within the
recommended disinfection time. With this proce-                             2.      Description of efficacy
dure, three lots of product are evaluated. In the test,
each lot of product is challenged with a large                                      A second major change is in the abandonment
challenge (10 6 CFU/ml) of five different micro-                                    of the calculated D-Values to descr ibe
organisms (Table 4). The microorganisms include                                     efficacy. A D-Value is the calculated time
Gram-negative bacteria (Serratia marcescens and                                     to reduce a population of microorganisms
Pseudomonas aeruginosa), Gram-positive bacteria                                     by 90% or by one-log unit. D-Values are
(Staphylococcus aureus), yeast (Candida albicans),                                  usually applied to thermal disinfection
and mold (Fusarium solani). The product is sampled                                  where the kill rate is linear (32). Since the
for survivors at 25, 50, 75, and 100% of the disin-                                 kill rates of CL disinfectants are not
fection time for bacteria, and then additionally at                                 linear, D-Values are neither predictive of

42                                                                          PDA Journal of Pharmaceutical Science and Technology
        antimicrobial activity nor are they reproduc-                 The Regimen Test
        ible for CL disinfectants. The method for
        determining acceptability in the ISO 14729                    The Regimen Test was designed to evaluate the
        procedure is a requirement for a specific                     efficacy of a disinfecting solution in a regimen
        log reduction of each challenge species in                    (Table 4). The contact lens care regimen as a
        order to demonstrate efficacy. This method                    w h o l e i s eva l u a t e d , i n c l u d i n g t h e r u b b i n g ,
        is desirable because it is simple and repro-                  rinsing, disinf ecting, and any other identified
        ducible. It has been used as a method to show                 manipulations. After treating each lens by the
        preservative efficacy for many years.                         steps outlined in the contact lens care regimen, the
                                                                      number of surviving organisms on the lens and
3.      Required validation                                           in the solution is determined by membrane
                                                                      filtration.
        A detailed method is provided for validat-
        ing the assay. The valida tion r e quires                     The Regimen Test is a carrier test, loosely based
        demonstration of the ability of the test                      upon the MCMIT. A carrier test is a test where
        system to recover survivors (33,46,45).                       objects, such as contact lenses, are inoculated with
                                                                      micr oorganisms and tested according la bel in
4.      Number of lots tested                                         structions for use. There are several important points
                                                                      of differentiation from the MCMIT, however, as de-
        Data from three lots are required and each                    tailed below:
        lot is tested with separate inoculum. This
        provides more information on the perfor-                      1.         Choice of challenge microorganisms
        mance of the product.
                                                                                 The Regimen Test uses the same challenge
5.      Low level disinfectants may qualify for the                              organisms as the Stand Alone Test. Again,
        “Regimen” test                                                           the major change is the use of Fusarium
                                                                                 s o l a n i a s t h e c h a l l e n g e o rga n i s m i n
        It was recognized that CL disinfectants                                  p l a c e o f t h e s p o i l a g e o rga n i s m A s p e r-
        must have low toxicity because of use in                                 gillus fumigatus.
        the eye. The benefits to the patient from
        these systems containing less toxic                           2.         Organic load
        chemicals outweigh any increased hazard
        due to lower bacterial efficacy. A provision                             The organic load is optional in this test,
        was made to allow solutions to be marketed                               in contrast to the requirements of the FDA
        as part of a recognized regimen if the                                   and the French lens challenge tests. The
        disinfecting solution alone showed a mini-                               o rg a n i c l o a d c o n s i s t s o f i n a c t iva t e d
        mum standard of efficacy. If a product                                   bovine serum and killed Saccharomyces
        meets these minimal standards, then it                                   cerevisiae. It is a laboratory model for
        q u a l i fi e s t o b e t e s t e d b y t h e R eg i m e n              deposits accumulated during wear, such
        Test. This minimal entry standard is in the                              as proteins, lipids, mucins, and other
        ISO 14729 procedure to assure that any                                   o rg a n i c c o m p o n e n t s ( 5 3 ) . H ow eve r, a
        candidate CL disinfectant has at least a                                 laboratory prepared organic load is not
        minimal level of antimicrobial activity. It                              the same as that found in tear deposits.
        wa s w e l l k n ow n t h a t t h e c o n t a c t l e n s                (2,18).
        rubbing and rinsing steps are capable of
        reducing the microbial load from an initial                   3.         Three lots
        inoculum of 106 CFU/lens to about
        10 3 CFU/lens (21,39,44). Thus, the combi-                               The efficacy of the regimen against each
        nation of preliminary regimen steps, such                                organism must be demonstrated with three
        r u b b i n g a n d r i n s i n g , a n d t h e a c t ive                different manufactured batches of product.
        disinfection step provide excellent removal                              Previously, the FDA allowed testing of only
        and kill of microorganisms.                                              a single lot of product.

Vol. 56, No. 1, January/February 2002                                                                                                    43
4.     Quantitative recovery                                              The design of CL disinfecting solutions should take
                                                                          into consideration the event of non-compliance. For
       The microorganisms from all solutions and                          example, the disinfection time should be appropri-
       lenses are recovered by membrane filtration                        ate for contact lens wear. Likewise, if the rubbing
       and plated onto an agar surface. Passing the                       step is eliminated, the product should be tested
       test is determined by recovery of a mini-                          under stress conditions (23). Although outside the
       mal number of microorganisms. The ISO                              scope of the ISO standard, additional testing of the
       14729 Regimen Test requires that for each                          CL disinfectant, such as other microorganisms, high
       microbial species, the average count for all                       levels of organisms, and organic soil, may be
       lots tested be no more than (NMT) 10                               considered depending on the particular patient
       survivors for each lens-solution combina-                          instructions for use of the product.
       tion per species. A total of 24 lenses per
       microbial species are tested. This is an                           Interpretation of the ISO Standard
       improvement over the MCMIT because the
       ISO 14729 procedure quantitates the survi-                         The ISO 14729 standard has two tiers of criteria
       vors, whereas the MCMIT was based on                               (Figure 1). The first tier is the Stand Alone Test
       turbidity (indicating microbial growth),                           and the second tier is the Regimen Test. The Stand
       which could have resulted from only a few                          Alone test gives insight into the performance of the
       microorganisms, or several million.                                CL disinfecting solution without the aid of the
                                                                          proven regimen steps, such as rubbing, rinsing, and
5.     Validation requirements                                            disinfection.

       The quantitative recovery allows a far more                        The Stand Alone Test has two sets of criteria,
       p r e c i s e va l i d a t i o n p r o t o c o l t h a n w i t h   the primary and secondary. If the CL disinfecting
       liquid recovery. The Regimen Test is vali-                         solution reduces the level of bacteria by an average
       dated to detect low numbers of viabl e                             greater than or equal to 3.0 log units and the level
       microorganisms from the test solution.                             of fungi by an average greater than or equal to 1.0


Table 5. Comparison of ISO 14729 performance criteria for bacteria at disinfection time.




44                                                                        PDA Journal of Pharmaceutical Science and Technology
log units within the recommended soaking period,                          The Regimen Test actually has more stringent
then the CL disinfectant meets the primary criteria                       criteria than the Stand Alone Test, because these
of the Stand Alone Test (Table 3). Meeting the                            criteria include the contribution of mechanical
primary criteria simply means that the CL                                 cleaning of the contact lens. A level of NMT
d i s i n fe c t a n t i s ex p e c t e d t o p a s s t h e R egi m e n   10 CFU/lens (Regimen Test) is approximately a
criteria, if it should be tested. Therefore, if the CL                    5 to 6-log reduction per microbial species, depending
disinfecting solution meets the primary criteria, it                      on the inoculum size. In comparison, the log re-
is exempted from further testing and can be labeled                       duction required to pass the primary criteria of the
as a disinfectant.                                                        S t a n d A l o n e t e s t i s a 3 . 0 - l o g re d u c t i o n f o r
                                                                          bacteria and 1.0-log reduction for fungi. Whereas,
If the CL disinfectant fails to meet the primary                          the Regimen allows no more than an average of 10
criteria, but passes the secondary criteria, then it                      survivors (CFU/lens), the primary criteria of the
qualifies to be tested by the second-tier Regimen                         Stand Alone test allows up to 1 X 10 5 (100,000)
Test. The secondary criteria are met if the sum of                        survivors of some species (CFU/lens) (Table 5).
the average log reductions for the three challenge                        However, the CL disinfecting solutions that passes
bacteria is at least 5.0 log units within the recom-                      the primary criteria are expected to also pass the
mended soaking period with a minimum of a 1.0                             Regimen criteria because of the contribution of
log reduction for any single bacteria (Table 3). The                      the rubbing and rinsing steps to the removal of
product cannot be classified as a CL disinfecting                         microorganisms.
solution or as part of a CL disinfecting regimen
according to the ISO 14729 standard unless it meets                       The Difference a Regimen Makes
the both the secondary criteria of the Stand Alone
test and the Regimen Test (Figure 1).                                     A r eg i m e n i s a ny p ro c e s s b y w h i c h a l e n s i s
                                                                          disinfected. It is the use directions on the label of
If the CL disinfectant meets this minimal level of                        each CL disinfecting product. Examples of label
activity, it qualifies to be tested by the Regimen Test.                  i n s t r u c t i o n s f r o m s eve r a l d i ff e r e n t m a r ke t e d
The Regimen Test evaluates the label instructions in                      products are summarized in Table 6.
the package insert for the entire disinfecting system
or regimen. The Regimen Test requires that the popu-                      The ISO 14729 infers that, if a CL disinfectant
lation of microorganisms be brought to an average level                   meets the primary criteria for disinfection of
of NMT 10 CFU/lens (Table 3). If the CL disinfecting                      contact lenses, then the CL disinfectant is exempt
regimen meets the Regimen criteria, it can be labeled                     from conducting the Regimen Test, because it is
as part of a CL disinfecting system.                                      assumed that if the CL disinfectant were tested

Table 6. Comparison of regimens of marketed products. a




a
    Descriptions are summarized from marketed product labels.

Vol. 56, No. 1, January/February 2002                                                                                                            45
Table 7. Comparison of Stand Alone Test results to Regimen Test results with and without Rubbing and
Rinsing steps for a 3% hydrogen peroxide system utilizing simultaneous neutralization of the active. a




a
    Data originally presented in poster (36).
b
    The primary criteria of the Stand Alone Test is an average of a 3.0-log reduction of the three bacteria and an average of a 1.0-log reduction of the two fungi.
c
    The criteria are an average of NMT 10 CFU/lens, which is equivalent to approximately a 5-log reduction.


Table 8. Effect of soil on Regimen Test.




according to the label instructions, then it would                                       Does Soil Make a Difference in the Regimen Test?
pass the Regimen Test criteria. This does not mean
that a CL disinfectant can be marketed without the                                       It has been documented in the literature that
appropriate rubbing and rinsing steps. For example,                                      laboratory prepared soil can neutralize the effec-
a 3% hydrogen peroxide system that meets the                                             tiveness of some hospital disinfectants, such as
primary criteria of the ISO 14729 Stand Alone Test                                       iodophors, quaternary ammonium compounds (28),
will also meet the Regimen Test criteria when                                            and chlorine (38). Similar findings were found for
tested with the appropriate rubbing and rinsing steps                                    a PHMB preserved contact lens disinfectant when
(Table 7). However, when the 3% hydrogen peroxide                                        high loads of microorganisms were introduced into
system is used without the aid of the rubbing and rins-                                  the product (48). However, the effect of soil is not
ing lenses, it will fail the Regimen Test (36).                                          seen when a rubbing or rinsing step is used prior to

46                                                                                       PDA Journal of Pharmaceutical Science and Technology
disinfection, since most of the soil is removed prior                       Worthiness of the ISO Disinfection Standard
to the disinfection step. Bell et.al., showed that there
was no difference between tests conducted with lenses                       The ISO 14729 CL disinfection standard will be a
coated with soil and clean lenses (with no soil) (1).                       very important standard. For the first time in the
The results are summarized in Table 8.                                      contact lens industry, there is consensus on the stan-
                                                                            dard by which CL disinfectants must perform to be
Easy Regimen to Meet Patient Needs                                          marketed within the U.S., Europe, and several other
                                                                            countries. There has been intense review, debate,
What the contact lens user frequently requests is an                        and revisions from all parties. The standard for CL
easy to use regimen; a regimen where the lens does                          disinfectants is much higher than the past. The
not have to be rubbed or cleaned prior to disinfec-                         implementation of the standard will result in a more
t i o n . A s s h ow n p r ev i o u s l y i n t h e c a s e o f             consistent quality between products. Today, what-
hydrogen peroxide systems, a lens cannot simply                             ever the regimen may be, CL disinfectants are tested
be dropped into a CL disinfectant and be expected                           by a standardized test procedure prior to approval
to be disinfected. The ISO 14729 standard was with                          or certification for marketing. The standard gives
the assumption that CL disinfectants would be used                          the consumer a better assurance of the performance
with the standard rub, rinse, and disinfect steps. The                      of the products that they purchase.
lens must be treated according to label instructions,
whatever that is. Products not using the standard                           Conclusions
regimen steps should prove their claim under stress
conditions. One CL disinfectant regimen with no                             The ISO 14729 procedure provides a more consistent
rubbing step reported its efficacy under stress                             procedure and a higher standard for CL disinfec-
conditions, such as efficacy against n umerous                              tants. The standard has influenced manufacturers
clinical and environmental isolates other than the                          to provide CL disinfectants that are now safer and
standard challenge organisms, using high loads of                           more effective than ever. In addition, simpler to use
organisms, in the presence of soil, after storage at                        d i s i n f e c t a n t s w i t h g o o d p e r fo rm a n c e a r e n ow
e l eva t e d t e m p e r a t u r e s , a n d d u r i n g e x t e n d e d   marketed. All are benefits to the consumer.
storage. This product was shown to meet both the
primary criteria of the Stand Alone Test and the
stringent Regimen Test requirements using a “no
rub” regimen (35,36,37).




Vol. 56, No. 1, January/February 2002                                                                                                           47
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