Pharmaceutical product development activities are highly interconnected in nature. For parenteral drug products, the prefilled syringe is generally considered a challenging container closure system, particularly in the case of vaccines with complex product design requirements. The authors describe a holistic and integrated approach to focus on the linkage of the prefilled syringe with the four phases of product design, development, operation, and control.
Vaccine product development in prefilled syringes—drivers and complexityThe goal of pharmaceutical product development is to design and establish the formulation composition and its manufacturing process to consistently deliver a drug product with all the appropriate quality attributes required for its intended efficacy and safety profile. A systematic approach according to the quality-by-design (QbD) concept is applied to achieve both the information and material deliverables during the product development lifecycle (1). Before work begins on the development of a new product, it is crucial to clearly define the quality attributes of the product with consideration of the end user’s needs in mind, commonly referred to as the target product profile (TPP) in the pharmaceutical industry. A TPP can be used to facilitate discussions with regulators regarding the anticipated label claims for a product (2). It can also be used for the private sector market, to help determine competition and associated pricing strategies (3, 4). Alternatively in the case of vaccines, a TPP can be used as a tool to engage and align with public health policy organization by working together to achieve the intended health impact (4, 5).
The definition of TPP according to the target disease/health policy and user requirement drives the design of the dosage form with selection of the primary container-closure system as an integral aspect to meet the delivery requirement. Drug products packaged in prefilled syringes essentially remove the withdrawal step from another container, such as a vial or ampoule, prior to administration. As a result, prefilled syringes offer a more convenient alternative to vials for the preparation and administration of injectable drugs. This results in improved provider/patient convenience and compliance, as well as product differentiation when combined with auto-injector delivery devices. There are many drivers and good reasons to have vaccines in the prefilled syringe presentation. First and foremost vaccines are complex biological entities; therefore, they must be administered by injection due to the lack of significant advance in alternative delivery technologies. From the technical point of view, one can imagine it is absolutely crucial to reduce the risk of wrong dose and also better dose precision; therefore, one can see the advantages of prefilled syringe as compared to vials. From a practical point of view, vaccines are sometimes driven by public health outbreaks because many doses could be given in a crowded setting, allowing simple administration with limited manipulation. This provides for less probability of handling errors in a prefilled syringe presentation, which is preferred. Lastly, there is a different economic factor than for example biologics and is driven by key stakeholders in the public health sector. The minimal overfill in a prefilled syringe as opposed to vial can also provide an economic advantage, because costs per unit must be low. In summary, there are clear scientific, practical, and economical drivers for developing vaccines products in prefilled syringes.
Vaccine product development is complex in many aspects. First, vaccine products are prophylactic as opposed to therapeutic, and more often than not, the target population is children and pregnant women, so the regulatory standard is high. Second, the product types are diverse such as recombinant proteins, glycoconjugates, virus-like particles, attenuated viruses, and live viruses. The dosing requirement is also challenging, in that doses are typically very small. Multiple antigens are often combined to reduce the number of injections, and adjuvants are added in some cases to boost the immune response. Lastly, the complex properties and interaction with prefilled syringe results in an acute challenge to vaccine manufacturers.