Masterarbeit

Accelerated Development of COVID-19 Vaccines: Clinical Data Gaps Identified by Health Authorities and Respective Post-Authorisation Activities ***

Barbara Petzold (2021)

Summary
Language: English
Coronavirus disease 2019 (COVID-19), an infectious disease with respiratory and systemic manifestations, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Within 20 months after the initial occurrence of COVID-19, more than 200 million cases of COVID-19 and almost 4.4 million COVID-19-related deaths have been reported globally. The development of safe and effective vaccines against COVID-19 is considered paramount to control the current pandemic and to help prevent future outbreaks.
Traditionally, it takes vaccine developers 10 to 15 years to reach marketing authorisation. In contrast, COVID-19 vaccines have been developed and authorised within less than a year. The application for an Emergency Use Authorisation (EUA) in the United States (US) and for a Conditional Marketing Authorisation (CMA) in the European Union (EU) was based on short-term positive interim clinical safety and efficacy data from a pivotal Phase 3 clinical trial with clinical development still ongoing.
The main objective of this thesis is to review and to discuss clinical data gaps and missing information which were identified by the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) when issuing a CMA/EUA for COVID-19 vaccines and to present respective post-authorisation activities. Due to the accelerated development of COVID-19 vaccines and early CMA/EUA uncertainties remain about duration of protection, efficacy against severe COVID-19 and asymptomatic disease (SARS-CoV-2 infection), vaccine-associated enhanced disease, safety and efficacy in certain subgroups (e.g. immunocompromised patients, pregnant women), and long-term safety. Risks associated with these data gaps and missing information can be minimised by post-authorisation studies, extensive post-authorisation safety surveillance and adequate labelling supporting a positive benefit-risk assessment after early clinical interim data.
Finally, this thesis presents an outlook how future vaccine development can be accelerated based on the experience from the expedited COVID-19 vaccine development. This includes the use of validated vaccine platform technology, adaptive/seamless clinical trial designs, overlapping of clinical trial phases, labelling flexibility, and expedited authorisation coupled with intensive post-authorisation surveillance.
Pages: 79
Annexes: 5, Pages: 29