Major bio/pharmaceutical companies and contract service providers leading the charge to bring COVID-19 vaccines to market are familiar with established good manufacturing practices (GMPs). To support manufacturers in the rush to develop a vaccine, FDA, in June 2020, released industry guidance (1) highlighting the development and licensure of COVID-19 vaccines.
For example, FDA noted in the guidance that no “accepted surrogate endpoints” to which clinical testing can aim currently exist. Without these target endpoints, there is likely no ability to form a reasonable prediction that a potential COVID-19 vaccine would demonstrate a clinical benefit. FDA has recommended that any vaccine development program should, therefore, follow a traditional route to approval, meaning the development programs should demonstrate the vaccine candidate’s safety and efficacy in protecting patients from infection by the SARS-CoV-2 virus and/or clinical disease that results from infection.
“The FDA Guidance highlights the pertinent CGMP [current good manufacturing practice] considerations for all vaccine manufacturing and serves as a reminder of statutory GMP expectations for COVID-19 vaccines specifically,” says Karolyn Gale, senior director, regulatory affairs, Emergent BioSolutions, a contract development and manufacturing organization (CDMO). The CDMO was granted a $628-million task order under an existing contract with the Biomedical Advanced 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 candidates through 2021. Emergent will manufacture vaccine drug substance at its Baltimore Bayview facility in Maryland and will manufacture drug product and conduct fill/finish operations 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, manufacturing, and controls (CMC) in the COVID-19 vaccine development landscape,” says Gale.
For drug substance and drug product manufacturing, the guidance emphasizes that data be provided showing adequate control over all source material used in the manufacturing 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 culture 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 carefully, thus highlighting the importance of early engagement with the agency further,” Gale states.
Recognizing the challenges
Three important challenges to overcome include being able to validate currently unproven platform technologies, demonstrating that the vaccine confers protection 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 messenger 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 vaccines coming from traditional established technologies.
In designing a vaccine, developers must establish a sufficient “indicator 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 potential, which can impact the vaccine’s relevance and delay launch.
Knowledge and technology transfer
Ensuring that the overall regulatory strategy for a vaccine product is understood by a CDMO facility/partner chosen by a vaccine developer is one of the biggest regulatory challenges currently, says Gale. This transfer of knowledge and strategy is especially challenging considering the speed with which a COVID-19 vaccine is needed. “This is accomplished by ensuring the appropriate contacts are in place between the two organizations and that the lines of communication are open between the two entities that allow for exchange of pertinent information in real-time. Pertinent information includes FDA (or other health authority) feedback that informs or changes the overarching strategy for either the facility or the product development,” Gale says.
“Another challenge we face currently 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 constantly shifting, and new information is coming in daily; however, decisions for the facility and/or process need to be made to move forward. Despite these challenges, FDA, BARDA, and innovator companies have been supportive throughout the process.”
“Manufacture of vaccines is a complex process that requires multiple 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 support their COVID products, we are accelerating these processes from years to months. The technical challenges we face relate to ensuring we have a robust and reproducible 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.
About the author
Feliza Mirasol is the science editor for Pharmaceutical Technology.
Article Details
Pharmaceutical Technology
Vol. 44, No. 11
November 2020
Pages: 50–52
Citation
When referring to this article, please cite it as F. Mirasol, “GMPs Guide COVID-19 Vaccine Manufacturing,” Pharmaceutical Technology 44 (11) 2020.
