Ritskes-Hoitinga Merel, Barella Yari, Kleinhout-Vliek Tineke
Department of Population Health Sciences, Institute for Risk Assessment Sciences (IRAS), Faculty of Veterinary Medicine, Utrecht University, Postbus 80163, 3508 TD Utrecht, The Netherlands.
Department of Clinical Medicine, Faculty of Health Sciences, Aarhus University Hospital, Palle Juul Jensens Boulevard 99, 8200 Aarhus N, Denmark.
Animals (Basel). 2022 Jul 5;12(13):1735. doi: 10.3390/ani12131735.
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 ( = 11 individuals representing five stakeholder groups in eight interviews and two written statements) and analysed relevant publications, policy documents and other grey literature ( = 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.
2020年12月21日，欧盟委员会批准了辉瑞/生物科技公司生产的BNT162b2新冠疫苗“复必泰”（Comirnaty）有条件上市。从科学家首次发现新冠病毒到这一时刻仅仅过去了12个月。这与疫苗研发和获批通常所需的十年时间形成了鲜明对比。许多人认为，所需动物试验的变化加快了“复必泰”和其他候选疫苗的研发进程。然而，很少有人概述所做的这些变化，也很少有人就疫情压力产生持久影响的可能性采访相关利益相关者。我们的研究问题是：包括监管机构和制药公司在内的利益相关者，在加速批准“复必泰”等候选疫苗的过程中，是如何处理体内动物模型相关要求的？我们采访了荷兰国家层面和欧洲层面的关键利益相关者（在8次访谈和2份书面陈述中，11个人代表了5个利益相关者群体），并分析了相关出版物、政策文件和其他灰色文献（共171份文件）。受访者观察到，与非疫情情况下的疫苗批准相比，“复必泰”疫苗的监管程序和要求有显著变化。具体而言，欧洲药品管理局（EMA）通过采用加速评估和滚动审查程序以实现快速有条件上市许可，积极推动了这些变化，减少了动物研究数量，接受了更多替代方法，允许临床前体内动物实验与临床试验并行进行，并允许重复使用早期疫苗研究的历史数据。制药公司则积极预期这些变化，并在研发阶段提供了来自非动物替代来源的数据。获批后，由于mRNA疫苗的全面特性，它们在所有批次放行时也仅可使用体外方法。制药公司对未来的变化持乐观态度，因为社会对动物使用存在担忧，并补充说，在他们看来，非动物替代方法通常能更快、更好且更便宜地取得成果。我们采访的监管机构对永久实施这些变化更为犹豫，因为他们担心安全问题引发的强烈反对以及不良反应的不确定性。我们的分析表明，EMA如何通过减少所需动物研究数量并推广替代方法，在危机时期缩短了审批时间线。它还凸显了制药公司对促成这些变化的意愿。有必要开展更多研究，以调查这些在科学和法规方面进一步替代的有前景的可能性，为更快的疫苗研发做出贡献。
