Self-injection technology has come a long way sincethe first devices were introduced in the early 1980s.Prefilled syringes are becoming more popular forself-injection, and auto-injectors are helping tosimplify their use in both existing and newtherapeutic areas. This article will review thedevelopment of self-injection technology over theyears and examine some of the key featuresincorporated into modern-day devices, as well aspossible future developments.

DEVELOPMENT OF THE TECHNOLOGY

The first ‘sophisticated’ self-injection device becameavailable in 1984, with the launch of the first insulin

pen injector. Pen injectors are essentially sophisticatedsyringes and were developed for the reliable and accurateself-administration of the first wave of biotechmolecules, such as insulin and human growth hormone(hGH). Auto-injectors have been on the market as longas pen injectors but, until the 1990s, their use wasrestricted to emergency situations such as epinephrinefor treating anaphylactic shock (EpiPen®). The firstprefilled syringe-based reusable auto-injector came inthe 1990s with the launch by Glaxo of a self-injectableformulation of its new anti-migraine productImigran®/Imitrex® (sumatriptan). A disposable auto-injector for a therapeutic protein was first launched in2005 by Amgen for its erythropoietic protein,AranespTM (darbepoetin alfa).

SELF-INJECTION DEVICES

There are various different types ofself-injection device available onthe market today:

The pen injector is a cartridge-based device designed for thefrequent – usually daily – manualinjection of hormone replacementtherapies. These therapies usuallyrequire weight-based dosing ordose titration, and injections arerepeated until the cartridge isempty – usually after one to twoweeks. The drugs in the multiple

Drug Delivery & Formulations

60 Innovations in Pharmaceutical Technology

Self-Injection Technology and TrendsModern-day self-injection devices incorporate a number of advancedfeatures which makes them more acceptable to patients, thereby saving on healthcare resources and costs.

Ian Thompson is Manager, Business Development, at Ypsomed AG, where he has been workingfor the last 10 years with pharma and biotech partners to develop and bring to market innovativeand reliable injection systems for self-administration. Ian has 20 years’ experience in the sellingand marketing of technical products, the last 14 of which have been spent in the field of medicaldevices. He has a degree in Biochemistry, a Masters in Biotechnology and an MBA from HenleyManagement College, UK

By Ian Thompson at Ypsomed

Delivery system

Reusable auto-injector platform

Figure 1: Early auto-injectors –EpiPen® and Imigran®-Pen

Figure 2: Auto-injector designed for SSI’s UltraSafe®

PassiveTM Delivery system

EpiPen®

Imigran®`

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61Innovations in Pharmaceutical Technology

devices, a ‘scale of convenience’ has been createdwhich includes prefilled syringes, safety syringes andauto-injectors. At the ‘least convenient’ end of thescale (1) would be a lyophilised drug in a vial, whichwould then have to be dissolved and drawn up into asyringe prior to injection. At the other end of the scale would be the fully disposable auto-injectorwhich would score a maximum of 10 in terms ofconvenience (see Table 1).

A simple prefilled syringe alone can bring muchconvenience to an injection therapy. This has beenwell-illustrated recently following the successfullaunch by Abbott of Humira® (adalimumab) in aprefilled syringe for the treatment of rheumatoidarthritis. But auto-injectors in combination with aprefilled syringe bring an additional level of ease-of-use and safety. For this reason, device companies and pharma partners are developing auto-injectorplatforms that are compatible with these increasinglevels of convenience.

dose cartridges require the use of preservatives, whileindividual doses are typically 0.5ml or lower in terms ofinjection volume. Pen injector patients are accustomedto injecting themselves manually with 29-31G penneedles, providing as ‘comfortable’ an injection as possible.

Auto-injectors, as their name implies, automaticallyinsert the needle and perform the injection (typicallyspring driven), and are usually designed for use with fillable or prefilled syringes. A key requirementfor auto-injection is the need for liquid-stableformulations in a prefilled syringe or cartridge-baseddrug reservoir.

Reusable auto-injectors have been used since the late 1980s for syringe-based hormone replacementtherapies, and are increasingly being used for newerwaves of biotech molecules as prefilled formulationsbecame available – for example, β-interferon fortreating multiple sclerosis (MS). Some of these drugsare injected daily, but many therapeutics are nowinjected weekly or less frequently, particularly those fortreating autoimmune diseases such as rheumatoidarthritis (RA) and psoriasis. Most of these newer drugsdo not contain preservative (monodose formulations)and have comparatively large injection volumes of upto 1ml.

The fully disposable auto-injector device is the obviousgold standard for self-injection. Here, the prefilledsyringe is already packaged in the auto-injector,providing both ease-of-use and convenience for thepatient. All the patient needs to do is remove the rubberneedle cap, press the device against the skin and start theinjection. The device performs the injection and theneedle is automatically covered and made safe, as thedevice is removed from the injection site. A keyprerequisite for these devices is the need for reliability;the injection must be completed every time, with an extremely low risk of failure. Patient feedback with disposable auto-injectors is important; thehandling should be intuitive and the device should givevisual and audible notification that the injection hasbeen successful.

SCALE OF CONVENIENCE FOR PRE-FILLED SYRINGES

In view of the savings in healthcare costs that can be achieved by expanding the use of self-injection

Reusable auto-injectors have been used since the late 1980s for syringe-based hormone replacement therapies,and are increasingly being used for newerwaves of biotech molecules as prefilledformulations became available – forexample, ββ-interferon for treating multiplesclerosis (MS). Some of these drugs areinjected daily, but many therapeutics arenow injected weekly or less frequently,particularly those for treating autoimmunediseases such as rheumatoid arthritis (RA) and psoriasis.

Device Scale of convenience

Lyophilised formulation 1

Luer syringe ↓

Pre-attached needle syringe ↓

Safety syringe ↓

Reusable auto-injectorand safety syringe

↓

Disposable auto-injector 10

Table 1: Scale of convenience for self-injection devices

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SAFETY FEATURES ANDSAFETY SYRINGES

The operation and safety featuresof auto-injector devices are beingcontinually improved. Currently,marketed reusable auto-injectorsdo not have complete needle safety,as they are generally used withstandard prefilled syringes withpre-attached needles. However, inthe normal clinical environment, itis the need for needle safety whichhas given rise to new safety syringeand safety delivery system productswhich are being fitted to prefilledsyringes. Increasingly, patients whoself-inject are concerned about therisks of needle-stick injuries tofriends or family in their midst,

and for the easy and safe disposal of the used product. Theylook for ‘safety’ – whether it is a syringe or an auto-injectorthat they are using.

The first generation safety syringe devices were ‘active’,requiring the user to ‘actively’ make them safe afterinjection; by contrast, the newer ‘passive’ devicesautomatically provide needle-safety after the injectionhas been completed. These new passive devices not onlyprovide needle-safety, but are also injection aids, whichmake it easier to perform injections. The passive devices– with their low activation forces – can also be used in conjunction with new generation reusable auto-

injectors. If the patient is still fearful of performing amanual injection with a safety syringe, then acompatible, reusable auto-injector can be madeavailable. This has the advantage that the same safetysyringe can be used in both the clinic and homeenvironment with the simple addition of an auto-injector for home care.

MARKET TRENDS

The market for self-injection devices – pens and auto-injectors – continues to show above-average growth as aresult of several factors. The surge in biotech-basedresearch means that many more protein therapeutics arereaching the market, driving demand for injectableproducts as a whole. Also, the increased incidence ofdiseases such as diabetes and the availability of therapiesfor previously untreatable conditions are expanding theinjectables market. The advanced features of modern-dayself-injection devices are making them much moreacceptable to patients. If patients can self-administertheir medications, then not only is it more convenientfor them, it also saves on healthcare resources and costs,making self-injection much more cost-effective.

More recently, the market has been impacted by theintroduction of prefilled syringes and auto-injectiondevices in new therapeutic areas, such as autoimmunediseases. Today, insulin still dominates the market,followed by hGH and newer therapies such as fertilitytreatment (FSH – follicle stimulating hormone) andosteoporosis (PTH – parathyroid hormone) (see Table 2).Disposable pen systems are generating increased interest,and pen needle safety and handling systems are becomingmore widely used, for example, needle covers, electronics,and automated needle insertion and injection.

The need for different platforms for different patientgroups is causing increased segmentation of the peninjector market. Patients with visual impairment (forexample, diabetics or the elderly) need special

requirements, as do those with motor disabilities(multiple sclerosis, rheumatoid arthritis, cancerand again, the elderly). Other specialsituations are short-duration therapies (lowmolecular weight heparin, infertility) andemergency treatments (migraine, anaphylactic

Hormone Replacement TherapiesInsulin

Erythropoietin

β-interferon

Follicle stimulating hormone (FSH)

Parathyroid hormone

Heparin

Parkinson’s

Autoimmune DiseasesMultiple sclerosis

Psoriasis

Allergies

Irritable bowel disorder

AIDS

Cancer

Emergency DrugsMigraine

Anaphylactic shock

Table 2: Main therapeutic areas for self-injection devices

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We focus on one thing— and that’s the

development of self-injection devices.

We have one vision— and that’s to be specialists

in our field. It is our purpose to use our expertise,

dedicated resources, and experience to provide

our customers the ultimate device solutions.

e-mail us at info@ypsomed.comon the web at www.ypsomed.com

©2005 Ypsomed AG

T H E P O W E R O F A S I N G U L A R F O C U S

t h e p o w e r o fC O N C E N T R AT I O N

the device becomes negligible when compared with theannual therapy cost.

When deciding whether to develop a product as a self-injection device, companies need to consider factors suchas the drug formulation and dosing, the competitiveenvironment, the proportion of patients self-injectingand their specific needs.

CONCLUSION

In summary, the market for self-injection devices – pensand auto-injectors – continues to grow at above-averagerates, based on patent-protected designs customised to pharma companies’ specific needs. Self-injectiontechnical features to provide safe and reliable use have byno means been exhausted, and the choice of the correctdevice requires careful selection and close collaborationbetween the drug manufacturer and the device company.

The author can be contacted atian.thompson@ypsomed.com

shock). Care with needles is an issue with AIDS and HCV(hepatitis C virus), while 10-15% of the population can beexpected to have a phobia of needles.

This wide range of needs can only be met withcustomised designs, taking into consideration indicationspecific patient characteristics. To minimise the risk ofpoor compliance, the most appropriate device anddedicated ergonomics are selected to make the injectionprocess as easy and intuitive as technically possible.

COST FACTORS

As auto-injector technology becomes more complex andthus more expensive, the therapeutic areas that they serve– and the number of patients willing to self-inject – mustbe large enough to justify investment in such a complexdevice. Also, if injections are performed more often thanonce-weekly, then device costs become a relevant factor;auto-injectors, for example, have over 10 componentsand cost significantly more than a basic safety syringe.For weekly or less frequent injections, the annual cost of

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