INTEGRATED PREFILLED SYRINGE TOOLBOX FOR VACCINE DEVELOPMENT
Successful development of a vaccine product in prefilled syringes requires careful evaluation of the interaction between the
formulation and primary packaging components. In support of each vaccine, a QbD approach will be used to design systematic
product and process development studies and ensure a comprehensive data package. It is, therefore, crucial that a platform
approach for these development efforts be implemented, in which there is detailed characterization and fundamental understanding
of the various component attributes and associated variability within the platform prefilled syringe systems. In addition,
the prefilled syringe system selected for the platform approach must also fit well with the existing manufacturing and production
capability. To achieve a robust and flexible prefilled syringe platform, it is also beneficial to form a strategic alliance
with a reliable supplier that has a good reputation of quality control. Processing and quality control compliance are vital
for a successful vaccine product development and subsequent licensure. In summary, we propose a holistic and integrated approach
to focus on the linkage of prefilled syringe in the following areas:
- Target disease/health policy/user requirement
- Formulation design
- Prefilled syringe components
- Manufacturing process (site and equipment)
- Business/supply chain/procurement
- Regulatory and quality compliance requirement.
It is important to recognize there is significant interdependence between these areas, where an integrated platform toolbox
is warranted and these six aspects are connected into the four phases of product design, development, operation, and control
(Figure 3). The product design phase involves integration of the prefilled syringe as a crucial part when considering the complex health
policy and user requirements imposed by different global geographic regions as well as private market competition. The product
development phase focuses on the prefilled syringe as an integral part of the vaccine product due to the multiple contacts
and potential interactions with the diverse molecular properties of antigens. In particular, particles characterization pertinent
to silicone interactions is crucial because vaccines are prophylactic treatment to elicit an immune response before sick.
Figure 3: Integrated platform toolbox approach for vaccine product development in prefilled syringe.
The emphasis of product operation phase is to link the prefilled syringe to the product performance per design requirements
and supplier process capability and quality control. As a result, a key focus will be on supplier collaboration to understand
their process capability and improvements. Lastly, quality control of supplier with respect to incoming components, as well
as manufacturing process with respect to both site and equipment, must be implemented with periodic review mechanism within
the regulatory compliance framework to assure quality vaccine products delivered to the patients.
In addition, the six areas are divided into nine categories with detail attributes under each category based on technical
considerations, prior project experience, and learning. These attributes can be summarized in a fishbone diagram, as shown
in Figure 4, to form the basis of risk assessment to select and implement different feasible options for a standard toolbox approach.
In summary, the standard work stream, when combined with a toolbox approach, will drive down the development risk with information
that allows plug and play, as well as supply of standardized component material that result in lower cost of goods. Furthermore,
the platform approach can be improved and is expandable with accumulated product experience in the future after joint efforts
with a formulation group and suppliers.
Figure 4: Fishbone diagram of detail attributes as basis for risk assessment for selection and implementation of prefilled
The benefit of using a standard set of prefilled syringe components consistently for a variety of products is that a solid
and robust data package can be established to support licensure application. These categories of information include:
- Description, general information, material of construction, method of manufacture
- Suitability according to the FDA container closure guidance document which encompasses protection, compatibility, safety and
- The quality control aspects such as incoming specifications, industry standards, etc.
- Stability results, for example, will reveal some of the common stability issues and challenges depending on the product types,
- Manufacturability when new products in the same set of prefilled syringe are being transferred to production facility, where
deep process knowledge of the platform prefilled syringe systems have been accumulated with definitive enhanced production
efficiency and quality control.
This is important because it's expected to provide all of this information in a submission as summarized in Table I.
Table I: General submission information requirement.