Pharmaceutical pipelines have been shifting for the last 20 years toward the development of biologics, which make up about 70% of drugs currently in development, observes Susanna White, mechanical engineer for Oval Medical Technologies. “The most recent innovations in biologics are presenting new challenges in the design of delivery platforms, pushing the limits of current glass-based technology,” she tells PMP News.
Long-acting injectables (LAIs), for instance, are being developed to provide slow-release capabilities, White says. The consequence is, however, “as with other biologics, a viscous formulation and complex fluid properties (e.g., suspensions and emulsions with non-Newtonian properties).”
Single-use autoinjectors typically consist of a pre-filled glass syringe, an injection mechanism for drug delivery, and a needle safety mechanism for safe disposal of the device, White says. But instead of using glass, designing primary drug containers (PDCs) from polymers such as cyclic olefins “unlocks the constraints of glass-based PDC systems through facilitating an integrated approach to device design,” she explains. “The cyclic olefin PDC provides the option to configure component geometry freely, whilst ‘designing-in’ strength to manage high viscosities (>100cP). This permits the delivery of complex drug formulations alongside the inclusion of a full range of features (e.g., automatic needle insertion, end of delivery feedback, and passive needle safety), within a simplified and compact form.”
White will be exploring such possibilities in her upcoming Pharmapack 2018 presentation, “Polymeric PDC Technology: An integrated approach towards better auto-injector design,” on February 7.
Susanna White, mechanical engineer for Oval Medical Technologies
“Glass syringes have a long history of use within autoinjectors and are widely accepted by the market,” says White. “However, they do have many known issues, some of which have led to autoinjector recalls.” She points to some common challenges with typical auto-injector designs:
- Lubricants risk contamination.
- Tungsten contamination from glass.
- Plunger stiction leading to delivery inconsistency, which can result in wet injections.
- Risk of glass breakage.
- Formulation viscosity and volume limitations.
- Large manufacturing tolerances.
- Complex supply chains reliant on specialist suppliers.
White provides the following 5 benefits of using polymers for drug formulations:
- Delivery speed consistency (preventing wet injections even when injecting challenging formulations e.g., non-Newtonian fluids). By eliminating the need for silicone lubricants in the container, far more consistent frictions can be achieved over time and this reduces delivery time variability.
- Shorter injection times for viscous formulations, without the risk of glass breakage. Polymers are much more robust than fragile glass PDCs allowing higher forces and greater delivery pressures to be achieved without container breakage.
- Needle depth consistency, reducing risk of adverse events. This is possible because there is a reduced number of components in the tolerance chain, there is the freedom to include features specifically designed to manage the needle position, and each polymeric component can hold improved tolerances when compared to glass.
- Improved user experience through smaller gauge needles, facilitated by the increased container pressures that can be achieved.
- Polymeric PDC components can also be molded with features that directly interact with device mechanisms, which can overcome user issues such as device recoil, variable use forces, and injection speed. Ultimately this reduces the impact on the user, whilst ensuring all required user interface features are present without compromise to overall device size or usability.
At Pharmapack, White will also explain an integrated approach toward better auto-injector design. “During the development of a combination device, two main streams of development occur: 1) the drug and 2) the delivery device. It is imperative that any device development process places equal importance on the delivery requirements of the drug, as well as the requirements of the user interface,” she advises.
Such requirements must be fully understood at an early design stage for optimal device design and performance. For instance, “the user interface should not be influenced by the forces required to deliver the drug and, similarly, the drug delivery mechanism should not be influenced by any force the user applies through the user interface,” White explains. “Regularly, these two sets of requirements conflict; biologics may require high delivery forces, whereas specific user populations may require low operation forces from the user interface. Part of the challenge for engineers is to accept this conflict and design around it effectively. It is possible to ‘decouple’ the conflicting requirements between the user interface and drug delivery mechanism through use of a polymer PDC.”
Another important step is drug characterization. “Oval has developed an injection characterization system (ICS) to thoroughly analyze a range of complex formulations and their properties, allowing an improved understanding of how they must be delivered,” she says. “This facilitates the correct autoinjector mechanism specification (e.g., needle bore, spring force, and container type), and also identifies factors with the potential to affect the user.”
White says that “a user-centric approach to the medical device development process is key in ensuring the design of devices that promote correct, safe, and effective use. The inclusion of human factors engineering from the outset of the development process allows for an understanding of user group needs, their anticipated limitations and the environment in which the device will be used. Ultimately, the knowledge space that human factors engineering generates allows minimisation of use-related risks and avoids inadequate device design which could compromise the effectiveness of the device user interface.”
At Pharmapack, Oval will be highlighting its subcutaneous platform, which White says “embodies this integrated philosophy to device design and is intended to improve clinical outcomes through the greater management of key device aspects such as needle depth or delivery time.”