By Rachel Legmann and Byron Rees
Vaccines have been around and proven as important life-saving tools since the 1790s. Yet, at the start of 2020 new development programs were lagging and there was unfounded controversy over their value.
All that swiftly changed in the spring of 2020, as the COVID-19 pandemic took hold globally. Vaccines became one of the hottest topics in industry and mainstream media practically overnight. But what does it really take to produce great vaccines?
While there is no one-size-fits-all platform approach for vaccine production, all platform manufacturing processes are built to simplify, de-risk and accelerate the development and manufacture of drug substances. Despite the risk-aversity of this industry, iterative improvements to platform processes have helped to increase rates of adoption in the past five to ten years. Advances like single-use technology and continuous manufacturing technologies have enabled more flexibility and ease of use, though standardization remains in flux.
The COVID-19 vaccine development rush is putting the power of platform technologies on full display and acting as a catalyst to advance innovation leveraging from gene therapy-based therapies and standardization. And while there is still progress needed, QbD methodology from the United States Food & Drug Administration offers valuable guidance on how to optimize a process using the right platform.
Guidance on proper QbD methodology includes leveraging prior knowledge where feasible; completing risk assessment, mechanistic models, design of experiments (DoE) and data analysis; and implementing process analytical technologies (PAT) to focus on establishing1:
- A quality target product profile (QTPP) that identifies the critical quality attributes (CQAs) of the drug product
- Product design and understanding including identification of critical material attributes (CMAs)
- Process design and understanding including identification of critical process parameters (CPPs), linking CMAs and CPPs to CQAs
- A control strategy that includes specifications for the drug substance(s), excipient(s), and drug product as well as controls for each step of the manufacturing process
- Process capability and continual improvement
- State-of-the-art risk management strategies and orthogonal approach to viral safety (including when the product is a virus)
- An integrated approach to ensure product safety through quality risk management (QRM)
Integration Enables Innovation
Today there are a myriad of final manufacturing environments including traditional facilities, hybrids, stick-builds, modular concepts, and prefabricated formats. Manufacturers are focused on leveraging integrated end-to-end-process solutions that look beyond the core process unit operations and extend to supporting every operation, including buffer preparation and fluid management. They need adequate performance characterization to get drug or vaccine candidates moving to the next stage in the development process.
This means that platform choices are being made based on performance attributes and real-world benefits such as usability, ergonomic design, scalability, and economy. Optimizing time, money, and quality are crucial to meeting market demands, and access to a range of options and support in building the right platform is necessary.
Building Platforms for Process Success
Pall Biotech works with customers to define and build scalable platforms for the life of a process with focused support teams to complement enabling technologies. The Accelerator℠ Process Development Services (PDS) team offers upstream, downstream, and analytical support, while the Scientific and Laboratory Services (SLS) team is available for ad hoc field-based customer and technical services or validation support. These teams can consult on the impact of selecting the best technology for each application. These may include evaluating single-use depth filtration over centrifugation for clarification of a monoclonal antibody or using a membrane-based purification to reduce empty viral vectors from full instead of ultracentrifugation. Similarly, this consultancy extends upstream to more fundamental decisions such as choices between using single-use suspension or adherent cell culture systems for viral vector production that scale easily ,instead of traditional roller bottle and flatware choices that do not.
The Allegro™ STR single-use stirred tank bioreactor portfolio leverages decades of bioprocess engineering expertise. Proven to deliver consistent, scalable suspension cell culture performance in both monoclonal antibodies and viral vectors. The iCELLis® 500+ fixed-bed bioreactor leads the market in supporting gene therapy drug commercialization for adherent cell culture. Integrated with downstream technologies like the Stax™mAx single-use clarification platform for depth filtration that can eliminate the need for centrifugation or process additives, vaccine manufacturers can achieve more rapid, robust performance without compromising on product quality and safety. This platform scales directly with a range of formats and sizes suitable for bench-top testing up to large-scale clinical production, so the manufacturer has a solution for the life of their process. Critical formulation and filling operations are supported by a range of sterilizing grade filters and automated solutions that ensure manual interventions are minimized to increase sterility assurance.
On Demand Innovation
The COVID-19 pandemic is proving what this industry can achieve when the pressure is on. The team at Pall Biotech is on demand to support advanced medicine production, like vaccines or cell and gene therapies, with end-to-end platforms and support for total process solutions leveraging extensive bioprocessing experience both in gene therapy and biologic therapeutic products.
Rachel Legmann is the Director of Viral Vectors & Gene Therapy Tech and Byron Rees is Senior Manger SLS for Pall Biotech.