by Rachel Legmann, Director, Viral Vectors & Gene Therapy Tech, Pall Biotech and Byron Rees, Senior Manager, Scientific and Laboratory Services (SLS), Pall Biotech
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?
Regulating Quality
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 Success
Balancing many variables at every step from bench to clinic can become challenging and stall commercialization without proper support and expertise backing your process development. Leveraging consultants who specialize in biopharmaceutical processes can help untangle the complexities of building a successful platform and streamline the journey from R&D to commercial manufacturing. Process development consulting services open up access to methods and technologies you may not have considered and brings a greater range of knowledge and experience on deck for optimizing your vaccine production platforms.
For example, 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. Their Accelerator Process Development Services team offers upstream, downstream, and analytical support, while the Scientific and Laboratory Services team is available for ad hoc field-based customer and technical services or validation support.
Teams like these can consult on the impact of selecting the best technology for each application. That 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 type of 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—rather than traditional roller bottle and flatware choices that do not.
The COVID-19 pandemic is proving what this industry can achieve when the pressure is on. Support and consultancy teams with on-demand service help ensure 24/7 operations can handle the ups and downs of an evolving pandemic.
About the Authors: Rachel Legmann, PhD, Director of Viral Vectors & Gene Therapy Tech at Pall Biotech, has more than 20 years of experience in the field of scalable biologics and gene therapy manufacturing of therapeutic products, viral vector and proteins for gene therapy and biologics. She completed her Ph.D. in Food Engineering and Biotechnology at the Technion-Israel Institute of Technology, Israel.
Byron Rees, Senior Manager of Science & Laboratory Services at Pall Biotech, received his BSc in Pharmacology from the University of Portsmouth, UK. He has gone on to work in QC for Microbiology and Analytical Chemistry at Pfizer. Since joining Pall in 2006, he has worked on all of Pall’s bioreactor technology developments.