title: Scientific and Regulatory Policy Committee Points to Consider Review: Inclusion of Reproductive and Pathology End Points for Assessment of Reproductive and Developmental Toxicity in Pharmaceutical Drug Development.
abstract: 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 end points across all study types; thus, inclusion and use of these end points are variable. The Scientific and Regulatory Policy Committee 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 end points 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 end points on a case-by-case basis is considered appropriate. Points to consider are summarized for inclusion of reproductive end points in general toxicity studies and for the informed use of pathology end points in reproductive and developmental toxicity studies.
authors.affiliation: Genetech, South San Francisco, California, USA halpern.wendy@gene.com.
authors.forename: Wendy G
authors.initials: WG
authors.lastname: Halpern
authors.affiliation: GlaxoSmithKline, King of Prussia, Pennsylvania, USA.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Ameri
authors.affiliation: Pfizer, Groton, Connecticut, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Bowman
authors.affiliation: Covance, Chantilly, Virginia, USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Elwell
authors.affiliation: Pfizer, Groton, Connecticut, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Mirsky
authors.affiliation: Incyte, Wilmington, Delaware, USA.
authors.forename: Julian
authors.initials: J
authors.lastname: Oliver
authors.affiliation: Regan Path/Tox Services, Ashland, Ohio, USA.
authors.forename: Karen S
authors.initials: KS
authors.lastname: Regan
authors.affiliation: WIL Research, a Charles River Company, Hillsborough, North Carolina, USA.
authors.forename: Amera K
authors.initials: AK
authors.lastname: Remick
authors.affiliation: NIEHS/NTP, Research Triangle Park, North Carolina, USA.
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Sutherland
authors.affiliation: Bristol-Myers Squibb, New Brunswick, New Jersey, USA.
authors.forename: Kary E
authors.initials: KE
authors.lastname: Thompson
authors.affiliation: Charles River Laboratories, Senneville, Quebec, Canada.
authors.forename: Claudine
authors.initials: C
authors.lastname: Tremblay
authors.affiliation: Food Safety Commission of Japan, Minato-ku, Tokyo, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Yoshida
authors.affiliation: Pfizer, Cambridge, Massachusetts, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Tomlinson
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods* / Q000592:standards*; D019983:Guideline Adherence; D006801:Humans; D010338:Pathology, Clinical / Q000379:methods / Q000592:standards; D018675:Toxicity Tests / Q000379:methods / Q000592:standards; D014116:Toxicology / Q000379:methods* / Q000592:standards*
keywords: clinical pathology; developmental pathology; preclinical research and development; reproductive system; safety assessment; teratology; toxicologic pathology