An overview of current and potential use of the minipig in developmental and reproductive toxicity testing

Although the minipig is recognized as a non-routine species in the latest revision of the International Council for Harmonization guideline on detection of reproductive and developmental toxicity for human pharmaceuticals (ICH S5(R3)), its practical use remains relatively limited in drug development programs. Concerns identified by pharmaceutical companies such as large active pharmaceutical ingredient (API) requirements, limited number of experienced laboratories, less extensive historical control datasets, a long gestation period, and minimal to no prenatal transfer of antibodies contribute to hesitancy in adopting the minipig. In addition, to date, the lack of any regulatory-approved drug with data from a minipig embryo-fetal developmental study, is an additional indicator of a reluctance to accept and develop this alternative model. The principal objectives of this manuscript are to address these concerns and to propose alternative non-clinical strategies that could expand the use of the minipig in developmental and reproductive toxicology testing. By encouraging broader dialog with pharmaceutical companies and health authorities, the goal is to facilitate acceptance of alternative strategies and study designs.