Formulation and Functional Considerations for Delivering Biologics in Prefilled Syringes

Prefilled syringes represent a win–win scenario for both end-users and manufacturers. This drug-delivery system is widely used across a range of therapeutic areas because of its broad acceptance among healthcare workers, patients, and caregivers. As a result, there is a lot interest in the development of biologic drug products in prefilled syringes within the bio/pharmaceutical industry. Graham Reynolds, vice-president and general manager, Global Biologics at West Pharmaceutical Services, Inc., shares with Pharmaceutical Technology the various aspects that have to be taken into account when developing a biologic drug product in a prefilled syringe.

PharmTech: What are the formulation considerations for prefilled syringes?

Reynolds: A drug product’s formulation is comprised of multiple raw materials, as are the components of prefilled syringes. It is ultimately the compatibility of these systems that will help to qualify the system for its intended use. Components of prefilled systems typically include pistons, syringe barrels, needles, and needle shields-all of which must be compatible as a system and with the drug product.

In addition, formulators often struggle with the challenges of optimizing volume and viscosity to ensure an effective concentration of drug product. With larger molecules, it may be difficult to develop a dose below the 1-mL volume (to fit within a standard 1-mL syringe) without producing a high-viscosity product that may be difficult to handle and require high forces to inject. In such cases, the use of a larger dose volume, administered with a larger syringe (2.25 mL is typically the next larger size), will be required. There may be limitations to the volume that can be injected quickly, and many companies are now considering the option of a wearable delivery system, rather than hand-held, for volumes in excess of 2 mL.

PharmTech: What are the functional considerations for prefilled syringes?

Reynolds: The prefilled syringe component with the maximum drug product contact area is the syringe barrel, which can have a major influence on drug product quality. The compatibility of the drug product with the barrel’s contact surface is critical to the drug product quality, while the break-loose and glide forces are key to the administration.

Conventional wisdom says that a better delivery system can lead to a better patient experience. Specifically, “better” means easier to handle, with plungers that move smoothly and with the same force, consistently, every time. Additionally, they should cater to the particular diagnosis-for multiple sclerosis patients, for example, the prefilled syringes should be designed to accommodate patients who may struggle with dexterity issues while handling smaller items.

PharmTech: What about the importance of lyophilization?

Reynolds: Because biologic drug products are often moisture and temperature-sensitive, they present new challenges around packaging and containment. To ensure optimized storage and moisture protection for their injectable drug products, biopharmaceutical companies are increasingly turning to the process of lyophilization for biologics and other drugs that are sensitive in liquid form or sensitive to their environment. Lyophilization is considered an ideal process for injectable drug products that may have a limited shelf life in solution. Typically, lyophilized products are packaged in a vial, although there are options to use a dual-chamber syringe in some cases. The use of prefilled syringes to contain diluents, combined with some form of vial adapter or transfer device, can be an option to ease the administration of lyophilized products.