Safety surveillance and challenges in accelerated COVID-19 vaccine development

Abstract

The COVID-19 pandemic, caused by a novel type of coronavirus, continues to infect people, increasing morbidity and mortality across the globe. Measures to slow the transmission of the virus have had limited impact, and people, businesses, and economies have suffered. The disease has disproportionally impacted elderly and individuals with certain pre-existing conditions and has highlighted health and social inequities in some racial and ethnic minority groups. The majority of those who contract the disease recover completely, but some experience long-lasting complications. Vaccines have the potential to end the pandemic, and through the intense collaboration of scientists in government and private sectors, more than 200 COVID-19 candidate vaccines have been or are being developed, using known platforms and previous experiences with severe acute respiratory syndrome (SARS), at unprecedented speed. The expectations for vaccine safety and quality in the setting of accelerated development are the same as during non-emergency times; however, challenges inherent with the circumstances of the pandemic situation provide opportunities to improve clinical trial conduct and strengthen pharmacovigilance systems. We have reviewed and analyzed existing PV guidelines and recommendations throughout the lifecycle of vaccine development with a focus on developing a global/worldwide effort for post-marketing vaccine safety surveillance.

Plain language summary: The Important Role of Pharmacovigilance in Accelerated COVID-19 Vaccine Development This is an extensive review that intends to address important aspects of COVID-19 vaccines' accelerated development and safety surveillance. It is focused on regulatory requirements for long-term safety monitoring, practical applications, and current global efforts in developing robust pharmacovigilance systems for post-authorization surveillance.Notably, different perspectives of authors from industry, academic institutions, and contract research organizations involved in drug safety were incorporated to reflect on various regulatory requirements and new developments in vaccine safety. All co-authors are current members of International Society of Pharmacovigilance (ISoP).

Keywords: COVID-19; equity; pharmacovigilance; safety; vaccine development.

Figure 1.

COVID-19 vaccine development. The typical timeline of vaccine development is at least 5 years, while the accelerating development can take 1–2 years, but irrespective of the development time spent, the vaccine must be safe at every phase while efficacy data are collected and evaluated. During phase I, the safe dosage range of the vaccine is estimated in a small number of healthy volunteers between 20 and 80 subjects who are closely monitored. Phase II is performed on a larger number (~100–300) of closely monitored patients to determine the dosage range. Phase III includes pivotal or registrational trials, and expanded safety studies. During phase III clinical trials, the efficacy needs to be demonstrated in randomized, double-blinded, controlled clinical trials. Endpoints might include endpoints related to clinical disease or immune response after demonstration of efficacy on clinical disease endpoints, and these are immune-correlated or surrogates of that protection. After completion of clinical phases, the BLA submission is performed to the regulatory authority, which will assess the efficacy and safety data to determine the risk/benefit ratio and recommend or reject the approval of a vaccine. The pre-approval inspection of the manufacturer’s facilities where the vaccine will be produced is required before the final regulatory decision. The approval process of a vaccine also includes the approval of the vaccine labeling, which is directed to healthcare prescribers to understand the indication of the vaccine, the dosage and route of administration, warnings and precautions, adverse events, and other vaccines’ characteristics for its proper use. Furthermore, clinical trial data are also used to support recommendations for the inclusion or not of a vaccine into national immunization program. The regulatory authorities might request post-marketing phase IV studies to continue the characterization of the safety profile and particularly the long-term safety and efficacy of the vaccine. ACIP, Advisory Committee on Immunization Practices, part of the CDC, which reviews to inform recommendations for vaccine use in the United States; BLA, Biologics License Application; CDC, The US Centers for Disease Control and Prevention, which supports medical use and access recommendations and a communication network for vaccine information; FDA, US Food and Drug Administration, which reviews to inform recommendations for vaccine use in the United States; IND, Investigational New Drug Application. https://www.cdc.gov/vaccinesafety/ensuringsafety/history/index.html