As innovations in medicine enable more biologics to reach the market, ensuring the efficacy and safety of the drug is a high priority for pharmaceutical manufacturers
And yet, the first thing that a patient sees when dealing with a drug for self-administration is the delivery system. An excellent delivery system can open the door to at-home self-injection for molecules that might previously have only been available through multiple injection or intravenous (IV) administration. Although a good injection device can’t make the drug better, there is a recognition that an inadequate device, or one that a patient struggles to use effectively and in compliance with the appropriate regimen, may have an impact on the outcome of that patient.
With the commercialisation of the first wearable self-injection system — Amgen’s Repatha (evolocumab) available in the once-monthly Pushtronex system — the landscape for injectable medication has changed. The system, which is the first-generation device from West’s SmartDose drug delivery technology platform, was many years in the making and its development followed a similar path to that of a drug. Through an ongoing innovation process, improvements have been made to the platform, including a greater variety of dose delivery options. While often slow in coming to market, taking the time to qualify how a new delivery system works – not only with the drug, but also with the end user – can help to improve drug product efficacy, as well as patient adherence and compliance with therapeutic regimens.
By partnering with a device or delivery system manufacturer throughout the drug development journey, pharmaceutical manufacturers will not only move to market with an approved, commercially viable drug delivery system, but will gain valuable insight into the drug product along the way.
When creating a drug delivery system, the goal is to ensure ease of use for the patient through minimal steps and a convenient format. As more biologic drugs enter the market, delivery systems need to be able to accommodate a range of dose volumes and injection times or rates, while still accommodating the patients’ desire for a small, simple system. At the same time, biopharmaceutical manufacturers are seeking to bring drugs to market quickly and optimise patient outcomes while ensuring a robust and reliable supply chain for their product. Once in the market, the drug must be proven to improve outcomes to support the higher cost of some newer therapies, so patient adherence and the ability to demonstrate outcomes through data are important factors.
When injecting a drug, the first thing a patient or caregiver sees is the delivery system — not the drug itself. A complex delivery system can create initial patient frustration and confusion, which may lead to an unwillingness to comply with therapeutic regimens if the process of injection is too complicated.
Simple systems, with excellent training and onboarding systems, easy access to help and additional information, and a professional look, can complement the drug product. If the pharmaceutical manufacturer begins to think of the system as an extension of the drug itself, making a good first impression will be of paramount importance.
Because bringing a drug delivery system from concept to market can take several years, it’s imperative that drug product manufacturers think about delivery options as early as possible in the development process. This process may start with an early evaluation of the container system, supported by analytical testing, which is used to help ensure that the primary drug packaging is a viable option for the drug product. In addition, the device should also be considered at an early stage, so that the drug delivery system is seen as a fully integrated solution.
Often, the selection of container and device become disconnected; however, the most successful approach may require a consideration of both the container and device as an integrated system early in the process. Such testing can provide valuable insight into the drug product and how it reacts with its primary packaging — and how the product and its delivery system are perceived and used by the patient.
The biopharmaceutical packaging industry, and indeed the pharmaceutical industry itself, is one of slow and careful innovation. An idea may spring to life today … but take several years before it is fully realised and ready to be introduced to the market. With an early stage molecule, it can be difficult to determine the product’s strength or final dose frequency.
Different analytical studies can help to determine the proper primary containment selection, including the need for barrier film-coated elastomers or a cyclic olefin polymer container instead of glass.
Daikyo Crystal Zenith cartridge
The final selection of materials may help to map out delivery options. Cyclic olefin polymers, such as the Daikyo Crystal Zenith cartridge used in the SmartDose drug delivery platform, can offer design flexibility as they can be moulded into a variety of shapes and sizes, and are highly break resistant when compared with glass.
As the molecule moves through the clinical phases and delivery becomes more structured, there is a need for speed, flexibility and expertise in the development of a delivery system. For example, Phase I may require multiple injections from a vial containment system; but, by Phase II, dose volume and frequency, as well as patient considerations, may drive the need for a delivery system such as prefilled syringe, autoinjector or wearable injector. The ability to fill the container at different stages must also be considered.
Working with a partner with in-house small quantity filling capabilities can provide samples during early phase development. Using a CMO or internal capabilities can also help to support fill-finish operations during scale-up. Biopharmaceutical manufacturers should seek out a partner with a range of different filling options — from clinical to commercial — and those that can easily adapt to handle unique containment systems.
As the drug manufacturer prepares to commercialise the product, patient adherence, onboarding and compliance must be considered with respect to drug delivery. In addition, it will be critical to consider what information is required to support product registration, including stability studies, human factor testing, device studies, etc. In preparation for commercialisation, it is also critical to consider the overall supply chain and provide a robust solution, including containers, drug, filling, device manufacture and assembly, secondary assembly of the device and drug container, patient services (training and adherence solutions) and a variety of other factors.
West has increased its capabilities in these areas to be able to partner with customers through the journey from the early molecule to the patient. Travelling the development pathway together can help to reach these patient-preferred options much sooner and prevent a move to market with a drug product that may cause adherence and compliance concerns owing to the delivery method.
As noted above, the first-generation SmartDose system, in the form of the Pushtronex, was the first commercial wearable self-injection system on the market. Since its original development, West has expanded the platform with new innovations and developments that have focused on the patient experience and meeting the needs of evolving drug pipelines.
Modern biologics are large molecules that may need high dose volumes to ensure the proper concentration is delivered; but, too frequent or too rapid dosing may cause pain to patients and limit adherence. Typical dose volumes have been in the 1 mL range; however, with more complex molecules and the desire for less-frequent dosing, volumes of up to 10 mL are required. Based on patient preference and the effectiveness of the drug, this type of volume requires either multiple injections of 1–2 mL or a single injection of a higher volume that should be administered during a longer period of time. Typically, it is desirable that a handheld device, such as an autoinjector, should deliver its dose within 10 seconds, whereas a device attached to the body (a wearable injector) can deliver slowly during a period of minutes or even hours, to help optimise drug absorption and patient comfort.
As the next generation of wearables moves through development, options for higher dose volumes, preloaded systems and the inclusion of findings around human factors and connectivity have helped to ensure that upcoming delivery systems offer a sophisticated-yet-simple solution to drug delivery. West experts are currently exploring options for self-injection at levels beyond 10 mL and continue to look at solutions that build on the learnings and findings from the initial SmartDose system success.
The typical drug development cycle can take several years. Optimising drug containment and delivery systems — from primary containment to commercialisation — during that time can help to ensure that when pharmaceutical manufacturers are ready to move to market, the delivery system will make a great first impression on the patient. By understanding the requirements of the drug product as well as the patient, continued innovation in wearable injectors will help move products to market with minimal risk and maximum benefit.
By partnering with experienced drug containment and delivery system manufacturers, companies may be able to shorten the drug development cycle by potentially avoiding unnecessary delays. As the next generation of wearables continues to build on the success of the first commercial self-injection product, ensuring that the patient is at the forefront of development innovations will help to create a great first impression and a lasting impact on adherence and compliance so that the drug product can do what it does best — help the patient.