Scientific and Regulatory Policy Committee (SRPC) Points to Consider Review1: Inclusion of Reproductive and Pathology Endpoints for Assessment of Reproductive and Developmental Toxicity in Pharmaceutical Drug Development

• Published in: Toxicologic pathology 2016-05, Vol.44 (6), p.789-809
• Main Authors: Halpern, Wendy G., Ameri, Mehrdad, Bowman, Christopher J., Elwell, Michael R., Mirsky, Michael L., Oliver, Julian, Regan, Karen S., Remick, Amera K., Sutherland, Vicki L., Thompson, Kary E., Tremblay, Claudine, Yoshida, Midori, Tomlinson, Lindsay
• Format: Article
• Language: English
• ISSN: 0192-6233; 1533-1601
• DOI: 10.1177/0192623316650052

Standard components of nonclinical toxicity testing for novel pharmaceuticals include clinical and anatomic pathology, as well as separate evaluation of effects on reproduction and development to inform clinical development and labeling. General study designs in regulatory guidances do not specifically mandate use of pathology or reproductive endpoints across all study types; thus, inclusion and use of these endpoints are variable. The Scientific and Regulatory Policy Committee (SRPC) of the Society of Toxicologic Pathology (STP) formed a Working Group to assess the current guidelines and practices on the use of reproductive, anatomic pathology and clinical pathology endpoints in General, Reproductive, and Developmental toxicology studies. The Working Group constructed a survey sent to pathologists and reproductive toxicologists, and responses from participating organizations were collected through the STP for evaluation by the Working Group. The regulatory context, relevant survey results, and collective experience of the Working Group are discussed and provide the basis of each assessment by study type. Overall, the current practice of including specific endpoints on a case-by-case basis is considered appropriate. Points to consider are summarized for inclusion of reproductive endpoints in general toxicity studies, and for the informed use of pathology endpoints in reproductive and developmental toxicity studies.