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10 BioPharm International eBook October 2020 www.biopharminternational.com Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the US Department of Health & Human Services, for the rapid, large-scale production of leading COVID-19 vaccine candi- dates through 2021. Emergent will manufacture vaccine drug substance at its Baltimore Bayview facility in Maryland and will manufacture drug product and conduct fill/finish oper- ations at its facilities in Baltimore Camden and Rockville, MD (2). The company currently has deals with Johnson & Johnson and AstraZeneca to manufacture their respective COVID-19 vaccine candidates (3). "As with all FDA guidance, it gives sponsors and manufacturers clearer insight into the FDA's current thinking on a topic and how they are leveraging and/or interpreting, in this instance, standing 21 [Code of Federal Regulations] CFR Part 601 regulations for chemistry, manufac- turing, and controls (CMC) in the COVID-19 vaccine development landscape," says Gale. For drug substance and drug prod- uct manufacturing, the guidance emphasizes that data be provided showing adequate control over all source material used in the manu- facturing of the vaccine, including the history and qualification of cell banks and virus banks as well as the identification of all animal-derived materials that are used for cell cul- ture and virus growth. "It is recognized that this guidance will not cover all the considerations necessary to satisfy all statutory and regulatory requirements for licensure. It further acknowledges that in some instances, platform knowledge could be leveraged, the specifics of this potential and the science they are based upon must be considered care- fully, thus highlighting the impor- tance of early engagement with the agency further," Gale states. RECOGNIZING THE CHALLENGES T hree impor ta nt cha llenges to overcome include being able to validate currently unproven plat- form technologies, demonstrating that the vaccine confers protec- tion against SARS-CoV-2 infection/ COVID-19 disease, and targeting an appropriate vaccine design (4). Vaccines being developed with unvalidated, unproven platform technologies (e.g., DNA- and mes- senger RNA-platform based vaccines) raise uncertainties about long-term safety and the ability to confer long- term immunity against COVID-19. These newer platform technologies may offer unique advantages (e.g., accelerating timelines), but vaccines developed from them may face greater regulatory scrutiny than vac- cines coming from traditional estab- lished technologies. In designing a vaccine, developers must establish a sufficient "indica- tor of protection" (4) (e.g., antibody response levels) to first demonstrate that the vaccine protects against COVID-19 and take into account the SARS-CoV-2 virus' mutation poten- tial, which can impact the vaccine's relevance and delay launch. KNOWLEDGE AND TECHNOLOGY TRANSFER Ensuring that the overall regula- tory strategy for a vaccine product is understood by a CDMO facil- ity/partner chosen by a vaccine developer is one of the biggest reg- ulatory challenges currently, says Gale. This transfer of knowledge and strateg y is especially chal- leng i ng consider i ng t he speed with which a COVID-19 vaccine is needed. "This is accomplished by ensuring the appropriate con- tacts are in place between the two organizations and that the lines of communication are open between the t wo entities that allow for exchange of pertinent information in real-time. Pertinent informa- tion includes FDA (or other health authority) feedback that informs or changes the overarching strategy for either the facility or the prod- uct development," Gale says. "Another challenge we face cur- rently is pursuing FDA feedback for the facility and its capabilities while keeping the interests of more than one client and/or COVID-19 vaccine candidate in mind," she continues. "The landscape is con- stantly shifting, and new informa- tion is coming in daily; however, decisions for the facility and/or process need to be made to move forward. Despite these challenges, F DA , B A R DA , a n d i n n o v at o r companies have been supportive throughout the process." "Manufacture of vaccines is a complex process that requires mul- tiple unit operations to be executed in accordance with CGMPs," Gale adds. "The development and scale up of a commercial manufacturing process takes up to several years. As we work with our partners to sup- port their COVID products, we are accelerating these processes from years to months. The technical challenges we face relate to ensur- ing we have a robust and reproduc- ible manufacturing process that results in high-quality product." REFERENCES 1. FDA, Guidance for Industry: Development and Licensure of Vaccines to Prevent COVID-19 (CBER, June 2020). 2. Emergent BioSolutions, "Emergent BioSolutions Joins US Government's Warp Speed Program in Landmark Public-Private CDMO Partnership for COVID-19 Vaccine Development and Manufacturing," Press Release, June 1, 2020. 3. Emergent BioSolutions, "Emergent BioSolutions Reports Financial Results for Second Quarter and Six Months Ended June 30, 2020 and Revises Upward Full Year 2020 Guidance," Press Release, July 30, 2020. 4. G. Agrawal, et al., "On Pins and Needles: Will COVID-19 Vaccines 'Save The World'?" www.mckinsey.com, July 9, 2020. BP Regulatory Sourcebook Regulatory Guidance