They may now be firmly established on the market, but auto-injectors must be further refined to cope with high-viscosity formulation issues around. Technology providers looking to develop next-generation devices are on the case, reports Steven R. Kaufman from Bespak Europe Ltd.
As increasing numbers of injectable biologics are coming to market, the demand for auto-injectors continues to rise steadily. Most of these drugs have been offered in a prefilled syringe with injection volumes ranging from 0.3–1.2 mL. However, in recent years, there has been a clear shift towards even higher volumes and/or higher viscosities. With most auto-injectors currently using a power source that is mechanical in nature and generally spring-based, challenges are becoming more apparent.
Biopharmaceutical companies are facing fierce competition in most key therapeutic areas. One way they are seeking to differentiate is through the device. Auto-injectors, pen injectors and pump-based systems are being examined to determine which is best suited to patient needs, can safely and effectively deliver the drug, and has the highest likelihood of contributing to compliance.
At the same time, some of the devices now offered or already on the market are not well positioned to address the needs of the next wave of biologics and injectables. Some key concerns that have arisen are maintaining injection times with a target time of less than 10 seconds, stalling and incomplete injections, and glass breakage.
Faster Injection Times
Injection time, in particular, is now a hot topic of discussion. A number of sources have raised concerns that regulatory bodies have a preference for short injection times that do not exceed 10 seconds. With the viscous nature of some injectables, or when there are issues such as drug to siliconization interaction, there can be problems achieving that target time — even when injecting volumes of 1.0 mL or less.
Clearly, for bolus and high-volume injections, longer injection times will be allowed. But for auto-injectors, especially those still using a 1 mL prefilled syringe, time is of the essence. How long a patient is able or willing to hold an auto-injector against their skin is a matter of debate.
To achieve a faster injection time or to overcome siliconization challenges, a simple approach has been to use a more powerful spring or to incorporate a spring with a better delivery force profile. In some cases, this can work quite effectively. In others, it can potentially lead to increased forces being applied to various components of the auto-injector that will remain under stress for years in the biopharma supply chain — and may cause the syringe glass to break prior to or during the injection.
This could prevent devices from working properly, meaning that patients don’t get the required dose of medication. These types of scenarios could also have a serious impact on the reputation of the company involved, having a knock-on effect with both patients and regulatory authorities. Given the high value of many biologics, recalling or having to dispose of just one or two batches of these combination products could amount to tens of millions of pounds in lost revenue, with an even greater impact on the trust factor — established with time but so easily lost.
Although spring-based auto-injectors continue to have an important role to play in the current market, new technologies — for auto-injector platforms, stoppers/valves for sequential injection and bolus injection systems — are coming on stream to address some of these concerns.
One development programme that has garnered a lot of interest is a new power source to help overcome the issues that spring-based auto-injectors can have with injectables. Based on proven valve technology, a small novel container of liquefied gas was developed as a new power source. The propellant, when released, provides sufficient energy, in the form of a pressurized vapour, to power drug delivery and other functions.
The dampened nature of this delivery mechanism prevents unnecessary impact on the primary container, which is ideal for either glass prefilled syringes or cartridges — helping to further minimize any chance of glass breakage. This system is also flexible in that it can offer a complete spectrum of variation to adapt to the needs of the drug, therapeutic area or the patient itself.
For example, by simply altering the propellant within a single container format, the injection time can be customized for the most viscous injectables. In addition, by being able to provide such an effective delivery performance with the use of the same footprint, the efficiency of the space utilized allows for the design of compact devices.
As a result, changes in delivery volume and viscosity can be accepted with minimal physical changes to a device, and without having a significant impact on device development programme timelines. High viscosities and high-delivery volumes can be handled with relative ease. For instance, 2 mL of a 200 cPs formulation can be delivered within about 10 seconds.
A broad range of primary containers can be used alongside the power device. Containers with a wider diameter offer no additional challenges; as such, 1 mL standard, 1 mL long and 2.25 mL syringes can be used without any considerable effect on performance. Furthermore, the nature of the drive mechanism ensures that the primary container is completely emptied once the device has been activated.
Several variations of the devices are available for clinical trials, and a range of industrial designs is being considered for the body of the auto-injectors to best suit patient needs.
Auto-injectors have now become a more accepted method of delivering injectables. However, an increasing number of biotech and pharma companies are facing difficulties with high-viscosity injectable formulations — and technology advances by market players are needed to overcome some of the known problems with conventional spring-based systems. Technology that can accommodate various primary containers, as well as high-viscous and high-volume injections, offers a competitive advantage.