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 NEEDLE-FREE INJECTION 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. CONCLUSION 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 email@example.com Innovations in Pharmaceutical Technology
"Needle-Free Drug Delivery Technology"