The Promises of Speeding Up: Changes in Requirements for Animal Studies and Alternatives during COVID-19 Vaccine Approval–A Case Study

SIMPLE SUMMARY: The COVID-19 pandemic led to intensive research into finding new vaccines for human protection. On 21 December 2020, the European Commission granted conditional marketing authorisation for the messenger RNA vaccine ‘Comirnaty’, produced by Pfizer (New York, NY, USA) and BioNTech (Mainz, Germany). This happened only twelve months after the first identification of the virus, whereas the development and approval of vaccines usually take ten years. Through document analysis and interviewing key expert stakeholders, we examined whether the role of animal studies and alternatives in this fast approval process had changed and, if so, whether this could lead to using fewer animal studies and more alternatives in the future. It turned out that in this case, for vaccine development and production, the number of animal studies performed and required had indeed declined, more alternatives had been used and accepted, human studies started earlier and ran in parallel with (rather than sequential to) animal studies, and regulators accepted historical data from earlier vaccine research. The Pfizer/BioNTech vaccine case illustrates the tremendous progress in quickly producing and authorising reliable, safe and effective vaccines, using fewer animal studies and more alternatives. It is time to study the broader implementation of these new procedures on a larger scale to benefit animals and humans. ABSTRACT: On 21 December 2020, the European Commission granted conditional marketing authorisation for the BNT162b2 COVID-19 vaccine ‘Comirnaty’, produced by Pfizer/BioNTech. This happened only twelve months after scientists first identified SARS-CoV-2. This stands in stark contrast with the usual ten years needed for vaccine development and approval. Many have suggested that the changes in required animal tests have sped up the development of Comirnaty and other vaccine candidates. However, few have provided an overview of the changes made and interviewed stakeholders on the potential of the pandemic’s pressure to achieve a lasting impact. Our research question is: how have stakeholders, including regulatory agencies and pharmaceutical companies, dealt with requirements concerning in vivo animal models in the expedited approval of vaccine candidates such as ‘Comirnaty’? We interviewed key stakeholders at the Dutch national and European levels (n = 11 individuals representing five stakeholder groups in eight interviews and two written statements) and analysed relevant publications, policy documents and other grey literature (n = 171 documents). Interviewees observed significant changes in regulatory procedures and requirements for the ‘Comirnaty’ vaccine compared to vaccine approval in non-pandemic circumstances. Specifically, the European Medicines Agency (EMA) actively promoted changes by using an accelerated assessment and rolling review procedure for fast conditional marketing authorisation, requiring a reduced number of animal studies and accepting more alternatives, allowing pre-clinical in vivo animal experiments to run in parallel with clinical trials and allowing re-use of historical data from earlier vaccine research. Pharmaceutical companies, in turn, actively anticipated these changes and contributed data from non-animal alternative sources for the development phase. After approval, they could also use in vitro methods only for all batch releases due to the thorough characterisation of the mRNA vaccine. Pharmaceutical companies were optimistic about future change because of societal concerns surrounding the use of animals, adding that, in their view, non-animal alternatives generally obtain faster, better, and cheaper results. Regulators we interviewed were more hesitant to permanently implement these changes as they feared backlash regarding safety issues and uncertainty surrounding adverse effects. Our analysis shows how the EMA shortened its approval timeline in times of crisis by reducing the number of requested animal studies and promoting alternative methods. It also highlights the readiness of pharmaceutical companies to contribute to these changes. More research is warranted to investigate these promising possibilities toward further replacement in science and regulations, contributing to faster vaccine development.