Evaluation of Non-Clinical Toxicity Studies of COVID-19 Vaccines

ABSTRACT

Absence of a relevant animal disease model and lack of the use of supportive studies have limited the process of rapid development of SARS-CoV-2 vaccines. This study has evaluated how the choice of species selection and study design affected the outcomes of the non-clinical toxicity studies of the various SARS-CoV-2 vaccine concepts. The study has been focused on safety aspects i.e. on the Developmental and Reproductive Toxicity (DART) and Repeated Dose Toxicity (RDT) studies. Rat and rabbitwere themost commonly used species in preclinical toxicity testing. Some COVID-19 vaccine candidates show a DART study design suboptimal for antibody transfer during lactation. The toxicity studies showed no serious adverse effects.Minor effectswere expected, i.e. local reactogenicity, immune response and macroscopic findings at the injection site. In addition, comments received during the EMA assessment of the vaccines have been evaluated and consisted most frequently of commentary on study design, species selection and missing data regardless of the utilized vaccine concept. Use of supportive platform studies often substantiated the commentary on these main three categories. Animal model-based toxicity testing has shown limited value in establishing safety of the vaccines, and, more importantly, low translational value in supporting clinical development. From a 3R perspective sponsors are encouraged to focus on products from the supportive platform, both with respect to DART and RDT studies. Regulatory emphasis on data obtained from vaccines with the same platform technology data can be used to support marketing approval of new vaccines.