Reproductive Toxicity: New Perspectives on Preclinical Studies for Vaccines
Marion F. Gruber, Ph.D., Center for Biologics Evaluation and Research, Food and Drug Administration
The Office of Vaccines Research and Review of the Center for Biologics Evaluation and Research of the US Food and Drug Administration has responsibility for regulating a broad spectrum of vaccine products for the prevention and therapy of infectious disease indications. The target population for these products frequently includes women of childbearing potential and, in certain instances, pregnant individuals. Under current FDA regulations (21 CFR 201.57 (f)(6)) the label for a licensed product must include a narrative information about the products teratogenic effects and effects on reproduction and pregnancy, as well as postnatal development. However, for most biological products including vaccines this subsection of the label contains a paucity of data from human clinical trials and minimal or no preclinical reproductive toxicity data. A number of FDA wide initiatives to address these concerns are ongoing, with the ultimate goal of providing additional relevant preclinical and clinical information for the estimation of risks imposed on women and/or the developing offspring. The Maternal Immunization Working Group within CBER has been charged with addressing requirements for the performance and design of preclinical reproductive toxicity studies for vaccines and to develop comprehensive policy in this area. The recommendations set forth by the maternal immunization working group are summarized in a guidance document for evaluation of the reproductive toxicity potential of vaccines indicated for maternal immunization as well as for women of childbearing potential. In addition, the guidance authored by the International Committee on Harmonization (ICH) entitled "Detection of Toxicity to Reproduction for Medicinal Products" addressing the design of animal reproductive/developmental toxicity studies has been used by CBER, where appropriate, to assess the reproductive/developmental toxicity potential for biological products including vaccines. The CBER approach to reproductive toxicity testing for vaccine products will be discussed.