IPT 20 2006 31/8/06 09:13 Page 60 Drug Delivery & Formulations Self-Injection Technology and Trends Modern-day self-injection devices incorporate a number of advanced features which makes them more acceptable to patients, thereby saving on healthcare resources and costs. By Ian Thompson at Ypsomed Ian Thompson is Manager, Business Development, at Ypsomed AG, where he has been working for the last 10 years with pharma and biotech partners to develop and bring to market innovative and reliable injection systems for self-administration. Ian has 20 years’ experience in the selling and marketing of technical products, the last 14 of which have been spent in the field of medical devices. He has a degree in Biochemistry, a Masters in Biotechnology and an MBA from Henley Management College, UK Self-injection technology has come a long way since pen injector. Pen injectors are essentially sophisticated the first devices were introduced in the early 1980s. syringes and were developed for the reliable and accurate Prefilled syringes are becoming more popular for self-administration of the first wave of biotech self-injection, and auto-injectors are helping to molecules, such as insulin and human growth hormone simplify their use in both existing and new (hGH). Auto-injectors have been on the market as long therapeutic areas. This article will review the as pen injectors but, until the 1990s, their use was development of self-injection technology over the restricted to emergency situations such as epinephrine years and examine some of the key features for treating anaphylactic shock (EpiPen®). The first incorporated into modern-day devices, as well as prefilled syringe-based reusable auto-injector came in possible future developments. the 1990s with the launch by Glaxo of a self-injectable formulation of its new anti-migraine product DEVELOPMENT OF THE TECHNOLOGY Imigran®/Imitrex® (sumatriptan). A disposable auto- injector for a therapeutic protein was first launched in The first ‘sophisticated’ self-injection device became 2005 by Amgen for its erythropoietic protein, available in 1984, with the launch of the first insulin AranespTM (darbepoetin alfa). Figure 1: Early auto-injectors – Figure 2: Auto-injector designed for SSI’s UltraSafe® EpiPen® and Imigran®-Pen PassiveTM Delivery system SELF-INJECTION DEVICES ® EpiPen There are various different types of self-injection device available on Delivery system the market today: The pen injector is a cartridge- Imigran®` based device designed for the frequent – usually daily – manual injection of hormone replacement therapies. These therapies usually require weight-based dosing or dose titration, and injections are Reusable auto-injector platform repeated until the cartridge is empty – usually after one to two weeks. The drugs in the multiple 60 Innovations in Pharmaceutical Technology IPT 20 2006 31/8/06 09:14 Page 61 dose cartridges require the use of preservatives, while Table 1: Scale of convenience for self-injection devices individual doses are typically 0.5ml or lower in terms of Device Scale of convenience injection volume. Pen injector patients are accustomed Lyophilised formulation 1 to injecting themselves manually with 29-31G pen ↓ needles, providing as ‘comfortable’ an injection Luer syringe as possible. Pre-attached needle syringe ↓ Safety syringe ↓ Auto-injectors, as their name implies, automatically Reusable auto-injector ↓ insert the needle and perform the injection (typically and safety syringe spring driven), and are usually designed for use Disposable auto-injector 10 with fillable or prefilled syringes. A key requirement for auto-injection is the need for liquid-stable devices, a ‘scale of convenience’ has been created formulations in a prefilled syringe or cartridge-based which includes prefilled syringes, safety syringes and drug reservoir. auto-injectors. At the ‘least convenient’ end of the scale (1) would be a lyophilised drug in a vial, which Reusable auto-injectors have been used since the would then have to be dissolved and drawn up into a late 1980s for syringe-based hormone replacement syringe prior to injection. At the other end of the therapies, and are increasingly being used for newer scale would be the fully disposable auto-injector waves of biotech molecules as prefilled formulations which would score a maximum of 10 in terms of became available – for example, β-interferon for convenience (see Table 1). treating multiple sclerosis (MS). Some of these drugs are injected daily, but many therapeutics are now A simple prefilled syringe alone can bring much injected weekly or less frequently, particularly those for convenience to an injection therapy. This has been treating autoimmune diseases such as rheumatoid well-illustrated recently following the successful arthritis (RA) and psoriasis. Most of these newer drugs launch by Abbott of Humira® (adalimumab) in a do not contain preservative (monodose formulations) prefilled syringe for the treatment of rheumatoid and have comparatively large injection volumes of up arthritis. But auto-injectors in combination with a to 1ml. prefilled syringe bring an additional level of ease-of- use and safety. For this reason, device companies The fully disposable auto-injector device is the obvious and pharma partners are developing auto-injector gold standard for self-injection. Here, the prefilled platforms that are compatible with these increasing syringe is already packaged in the auto-injector, levels of convenience. providing both ease-of-use and convenience for the patient. All the patient needs to do is remove the rubber Reusable auto-injectors have been needle cap, press the device against the skin and start the injection. The device performs the injection and the used since the late 1980s for syringe- needle is automatically covered and made safe, as the based hormone replacement therapies, device is removed from the injection site. A key and are increasingly being used for newer prerequisite for these devices is the need for reliability; the injection must be completed every time, with waves of biotech molecules as prefilled an extremely low risk of failure. Patient feedback formulations became available – for with disposable auto-injectors is important; the β handling should be intuitive and the device should give example, -interferon for treating multiple visual and audible notification that the injection has sclerosis (MS). Some of these drugs are been successful. injected daily, but many therapeutics are SCALE OF CONVENIENCE now injected weekly or less frequently, FOR PRE-FILLED SYRINGES particularly those for treating autoimmune In view of the savings in healthcare costs that can diseases such as rheumatoid arthritis be achieved by expanding the use of self-injection (RA) and psoriasis. Innovations in Pharmaceutical Technology 61 IPT 20 2006 31/8/06 09:14 Page 62 Table 2: Main therapeutic areas SAFETY FEATURES AND injectors. If the patient is still fearful of performing a for self-injection devices SAFETY SYRINGES manual injection with a safety syringe, then a Hormone Replacement Therapies compatible, reusable auto-injector can be made Insulin Erythropoietin The operation and safety features available. This has the advantage that the same safety β-interferon of auto-injector devices are being syringe can be used in both the clinic and home Follicle stimulating hormone (FSH) continually improved. Currently, environment with the simple addition of an auto- Parathyroid hormone marketed reusable auto-injectors injector for home care. Heparin do not have complete needle safety, Parkinson’s as they are generally used with MARKET TRENDS standard prefilled syringes with Autoimmune Diseases Multiple sclerosis pre-attached needles. However, in The market for self-injection devices – pens and auto- Psoriasis the normal clinical environment, it injectors – continues to show above-average growth as a Allergies is the need for needle safety which result of several factors. The surge in biotech-based Irritable bowel disorder has given rise to new safety syringe research means that many more protein therapeutics are AIDS and safety delivery system products reaching the market, driving demand for injectable Cancer which are being fitted to prefilled products as a whole. Also, the increased incidence of Emergency Drugs syringes. Increasingly, patients who diseases such as diabetes and the availability of therapies Migraine self-inject are concerned about the for previously untreatable conditions are expanding the Anaphylactic shock risks of needle-stick injuries to injectables market. The advanced features of modern-day friends or family in their midst, self-injection devices are making them much more and for the easy and safe disposal of the used product. They acceptable to patients. If patients can self-administer look for ‘safety’ – whether it is a syringe or an auto-injector their medications, then not only is it more convenient that they are using. for them, it also saves on healthcare resources and costs, making self-injection much more cost-effective. The first generation safety syringe devices were ‘active’, requiring the user to ‘actively’ make them safe after More recently, the market has been impacted by the injection; by contrast, the newer ‘passive’ devices introduction of prefilled syringes and auto-injection automatically provide needle-safety after the injection devices in new therapeutic areas, such as autoimmune has been completed. These new passive devices not only diseases. Today, insulin still dominates