Retrospective Evaluation of the Use of Nonhuman Primates for Fertility Assessment of Marketed Medicinal Products (P201)

Monday, November 18, 2024

5:00 PM - 6:30 PM CT

Presenting Author(s)

Puck Roos

PhD candidate
Utrecht University (NL), Medicines Evaluation Board (NL)
Utrecht, Utrecht, Netherlands

Co-Author(s)

Diann Blanset, PhD, DABT

Highly Distinguished Research Fellow
Boehringer Ingelheim
Ridgefield, Connecticut, United States
Peter J.K. van Meer, PhD

Senior Assessor
Medicines Evaluation Board
Utrecht, Utrecht, Netherlands
Shermaine Mitchell-Ryan

Health and Environmental Sciences Institute
Washington, District of Columbia, United States
Peter Theunissen

Medicines Evaluation Board
Utrecht, Netherlands
Katie Turner, PhD

Associate Scientific Director
Johnson & Johnson Innovative Medicine
Spring House, Pennsylvania, United States
Ronald L. Wange, PhD

Associate Director for Pharmacology and Toxicology
US Food and Drug Administration, Center for Drug Evaluation and Research
Silver Spring, Maryland, United States
Christopher Bowman, PhD, DABT

Research Fellow
Pfizer Worldwide Research
Groton, Connecticut, United States

Reproductive toxicity assessment is conducted to detect potential adverse effects of medicinal products on fertility. When non-human primates (NHP) are the only pharmacologically relevant test species, effects on fertility parameters can be evaluated in NHP. We have retrospectively evaluated fertility assessment in NHP.
Our database consists of compounds submitted for marketing approval to the European Medicines Agency or approved by the US Food and Drug Administration between 2011-2022. Compounds with ≥1 GLP-compliant repeat-dose toxicity or fertility study in NHP were included. Information on compound characteristics, study design, effects on fertility parameters and labeling was obtained from publicly available documents.
In total, 263 compounds with 668 NHP studies were included. NHP age was reported for 49.9% of studies. NHP sexual maturity was reported for 18.0% of studies. Adverse effects on fertility parameters in NHP were reflected in the label of 22 compounds (8.4%). For none of these 22 compounds were sexually mature NHP vital to inform infertility risk assessment. Effects were predictable based on mechanism of action, or adverse effects were also observed in rodent studies.
In conclusion, the value of fertility assessment in NHP for approved medicinal products appears to be low. For small molecules, rodent studies were sufficient for risk assessment. For biologicals, a weight-of-evidence approach could be used. This would reduce the need for sexually mature NHP in drug development. Additionally, when there are scientifically valid reasons to use NHP for fertility assessment, sexual maturity status should be established prior to study initiation and reported in public documents.