Needle-Free Drug Delivery Technology by asafwewe


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									     Drug Delivery & Formulation

     Needle-Free Drug
     Delivery Technology
     The needle-free industry now has a broad range of excellent technology
     to meet customer needs; the only remaining barrier lies with the
     pharmaceutical and biotechnology companies themselves.

     By Dr Roger G Harrison, Consultant to Antares Pharma, Inc

     Dr Roger G Harrison has been a Consultant to Antares Pharma since September 2004. Prior to that he had been
     the Chief Executive officer, President and member of the Board of the Company since March 2001. Previous to
     that, he held various positions at Eli Lilly and Company for more than 25 years, with his most recent role being
     Director of Alliance Management from May 1999 until February 2001. Other positions at Eli Lilly included Global
     Product Team Leader, Director, Development Projects Management and Technology Development and Planning,
     and Director of Biochemistry Research. He is the author of numerous publications, has contributed to four books
     and holds nine patents. Dr Harrison earned a PhD in Organic Chemistry and a BSc in Chemistry from Leeds
     University in the UK and conducted postdoctoral research work at Zurich University in Switzerland.

     All parents can relate to the anguish felt when an infant    players now compete on the relative sophistication
     screams and protests at the sight of a vaccination           of their delivery technology. If pundits are to be
     needle. Later in life, the screams may abate but             believed, the next innovation in this sector will
     significant misgivings usually still exist about the         be pulmonary inhalation, which is being developed
     insertion of a needle for delivery of vaccines or            (at very significant cost) by Pfizer, Lilly and
     therapeutic agents, with relief when the process is over.    Novo-Nordisk in association with specialty drug
     For some, especially those suffering from chronic            delivery companies.
     diseases requiring injectable products, this process is an
     ongoing reality of daily life – accepted, but always with    Other companies are recreating drugs by extending their
     the hope that something new will replace the ritual of       apparent half-life through the use of depot injection
     needle insertion.                                            systems or by making structural changes that
                                                                  delay metabolism and clearance. Interferon and
     The industry has invested heavily in finding solutions to    erythropoietin are two examples of drugs that have
     this challenge without generating a universal solution.      undergone these changes – the result being less frequent
     The reasons for this investment are obvious – there are      injections for the patient. Commercial sales of such
     an increasing number of biotechnology products that          products have reinforced the view that patients and
     can only be given by injection. It is estimated that there   health care providers want to reduce or eliminate the
     are about 350 biotechnology products currently in            need for needles whenever possible. The more elusive
     clinical trials, and potentially 190 of these will be        search for oral delivery approaches for these complex
     on the market by 2005-2006. This compares with just          molecules has also been explored with encouraging
     10 such products on the market in the early 1980s.           results being generated by Emisphere Technologies, Inc,
     There is also clear evidence that the market for existing    BioSante Pharmaceuticals, Inc and Nobex Corporation,
     products is being increasingly differentiated through        among others.
     delivery technology.

     Using the insulin market as an example, the use of
     conventional vials with needles and syringes by
     patients with diabetes has dwindled, particularly
     outside of the US. Pumps and elegant ‘pen’ injectors                  Figure 1: The Antares Pharma Medi-Jector
     have increasingly taken market share, and major                          Vision Needle-Free Injection Device

60                                                                               Innovations in Pharmaceutical Technology
However, with all of these high-profile efforts to seek a
solution to less frequent injections with needles, there
has been a ‘sleeper’ technology already in existence – one
that offers all of the sought-after benefits. That solution
is needle-free or jet injection technology. This technology
– first described in 19th Century France and first
commercialised in the US in the 1960s – has been
relatively dormant in terms of market impact for many
years, despite being approved and available for use with
insulin and human growth hormone in the US and other
parts of the world. Several companies are active in the
further development of this technology (including
Antares Pharma, Inc, Aradigm Corporation, BioJect
Medical Technologies, Inc and BioValve Technologies
Inc), and there are industry associations charged
with promoting an awareness of the benefits of needle-
free systems.

Needle-free technology offers the very obvious benefit
of reducing patient concern about the use of a needle.
Additional benefits include a very fast injection
compared with conventional needles and no needle
disposal issues. Devices are available in re-usable and
disposable forms, for home or physician office use, and
also in versions for multiple patient, institutional uses.
The re-usable devices are intended for use in
association with chronic diseases, such as diabetes,
when injections are given on a daily basis for
prolonged periods of time. The disposable, single-use
devices are pre-filled with drug, used once and then
discarded. These are considered ideal for emergency
needs (for example, treatment of severe allergic
reactions), for intermittent needs (for example,
breakthrough pain or migraine attacks), or for office-        most effective designs in order to create devices that meet   Figure 2: Filling the
based vaccinations. Devices are also being developed          customer expectations of transparency of use and quality      Antares Pharma Medi-
                                                                                                                            Jector Vision Needle-
for mass vaccination (DCI, Inc, Felton International)         of injection.
                                                                                                                            Free Insulin Injector
that could help overcome the challenges of disease
transmission through re-use of needles that can occur         Perhaps it is this long history in reaching the current       The device can be
in developing countries.                                      point of sophistication that such devices have now            used with all brands
                                                                                                                            of U-100 insulin in
                                                              achieved that remains a barrier to their widespread
                                                                                                                            standard 10ml vials.
All of the devices operate by the same principle of           adoption – many physicians and decision-makers within
creating a high pressure jet of liquid – containing the       the pharmaceutical industry have been aware of some of
drug – that penetrates the skin. Through effective            the stories associated with needle-free technology, and
control of the pressure, the device can deliver the drug      have not been prepared to accept that the technology has
solution (or suspension) into the subcutaneous, sub-          continued to evolve. Such stories include pain on
dermal or intramuscular layers, depending on the              injection, poor quality of injection, and bruising and
required application. Power sources are typically springs     bleeding at the injection site. Some of these stories
or compressed gas. While the principle of operation is        are factual, some exaggerated, others anecdotal – but
simple, in reality, many years of engineering effort have     most of the past issues appear to have been overcome in
been put into understanding ideal pressure curves and         the current generation of technologies. Most of the

Innovations in Pharmaceutical Technology                                                                                               61
     companies working in this sector have their own or         THE IMPACT OF ADVOCACY GROUPS
     independently generated data showing an overwhelming       There are also advocacy groups emphasising the
     preference for needle-free technology by patients when     importance of considering needle-free options that
     they are given a choice.                                   can begin to influence perceptions. One of these, the
                                                                Association of Needle-Free Injection Manufacturers
     How, then, can this preference be converted into a         (ANFIM), was established in 1997 to create a
     significant market presence? There are some signs          positive, professional image for the needle-free
     of progress. For example, Serono uses BioJect’s needle-    industry through providing exposure, education and
     free device (cool-clickTM) in association with its         information to health care customers. ANFIM
     human growth hormone in the US, and Ferring                recently announced changes in its board structure
     Pharmaceuticals uses Antares Pharma’s Vision® device       with Mike Kasprick, Executive Director of
     for its human growth hormone in Europe. Also, Eli          Business Development for Antares Pharma, becoming
     Lilly and Company has licensed Antares Pharma’s            chairperson for the group. Commenting for this
     technology for use with the diabetes and obesity           article, Mr Kaspick said:
     products in its portfolio. The benefits for
     pharmaceutical companies are obvious in that,              “We believe that we have in our hands a general solution
     compared with investments in other delivery                to how injectable drugs can be given less invasively. Not
     technologies (for example, pulmonary delivery), the        only can this benefit the pharmaceutical industry in
     development of a needle-free system is likely to require   increasing product sales, it has the added potential to
     – from a regulatory viewpoint – the demonstration of       increase compliance with dosage regimens and
     pharmacokinetic equivalence of drug delivery by needle     improved outcomes. In the US alone, direct and indirect
     and needle-free systems, the lack of breakdown of the      costs of managing diabetes and its consequences cost
     drug through shear stress at the jet nozzle and a          $132 billion. If poor compliance with injection therapy,
     conventional device submission. There has been no          and hence poor control of the disease, is a factor in this,
     requirement for extensive safety and efficacy studies,     then even a small shift to needle-free delivery could
     which typically drive the costs of development into the    provide substantial benefit. I will be working through
     hundreds of millions.                                      ANFIM to create the greater awareness that can

                                                                                 Figure 3: The Antares Pharma Medi-
                                                                                 Jector Vision Insulin Injector Supply Kit.

                                                                                 The pack includes: Medi-Jector Vision
                                                                                 Injector, injection supply start-up kit,
                                                                                 carrying case with compartments
                                                                                 for extra supplies and insulin vials,
                                                                                 instruction manual and training video.

62                                                                            Innovations in Pharmaceutical Technology
promote a better understanding of the opportunity
represented by this technology”.

Another lobbying group active in this area is the National
Alliance for the Primary Prevention of Sharps Injuries
(NAPPSI). This group was founded to promote the
primary prevention of sharps injuries and to influence
laws, protocols and practices in the health care
environment. The US Occupational Health and Safety
Administration (OSHA) has estimated that about 5.6
million health care workers in the US are at risk of
occupational exposure to bloodborne pathogens, with an
estimated 800,000 medical sharps injuries occurring each
year. Sharps injuries can occur with lancets, suture needles,
syringe needles, scalpels and other sharp devices, with the
majority of injuries being reported by nurses. NAPPSI is
promoting safer alternatives in all of these areas, including
the use of needle-free systems where applicable.

In the developing world, there are major challenges
of disease transmission through re-use of needles.
Organisations such as the World Health Organization
(WHO) and Centers for Disease Control (CDC), and
groups such as The Gates Foundation have supported
the development of needle-free alternatives, particularly
for vaccine delivery.

As never before, there appears to be a tremendous
opportunity for needle-free technology to have a major
impact: drugs in development require less invasive ways
of delivery to realise their full benefit; several alternatives
have proven high-risk and high-cost to develop; more
sophisticated customers are demanding better approaches
to drug delivery; poor compliance is recognised as an issue
associated with the escalation of health care costs; lobby
groups are actively promoting the reduction in needle-use,
federal and state legislation is discouraging the use of
needles where alternatives are available; and the small
needle-free industry now has a broad range of excellent
technology that can meet customer needs. If the
technology meets the end-customer needs, the remaining
barrier must be within the pharmaceutical and
biotechnology industries. While this appears to be
changing, it is likely that dramatic change may occur only
when a large pharmaceutical or biotechnology company
adopts needle-free technology and demonstrates its
versatility, acceptance and value in a major therapeutic area.

The author can be contacted at

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