Pre- and postnatal developmental toxicity study design for pharmaceuticals.
Assessment of potential developmental and reproductive toxicity of human pharmaceuticals is currently guided by the ICH S5(R2) document. The studies that assess the hazard of both pre- and postnatal exposure are predominantly conducted in rodents (rat and mouse). Utilizing the collective experience of the authors, acceptable designs for both the range-finding and definitive studies are presented with detailed descriptions for the presentation of data. In addition, the suggested initiation and then total duration of these studies in relation to clinical studies are described. Optional parameters that may be included in the studies, as well as possible combination with other study designs are discussed. The details described herein will assist all laboratories performing these studies, individuals who need to plan for the studies, and regulatory agencies that ultimately review these studies.
Bailey
Graham P
GP
Johnson and Johnson PRD, Janssen Pharmaceutica, Beerse, Belgium. gbailey1@its.jnj.com
Wise
L David
LD
Buschmann
Jochen
J
Hurtt
Mark
M
Fisher
J Edward
JE
D000818:Animals; D004305:Dose-Response Relationship, Drug; D064420:Drug-Related Side Effects and Adverse Reactions; D047108:Embryonic Development / Q000187:drug effects*; D047109:Fetal Development / Q000187:drug effects*; D048788:Growth and Development / Q000187:drug effects*; D007390:International Agencies; D007391:International Cooperation; D007880:Legislation, Drug; D051379:Mice; D004364:Pharmaceutical Preparations / Q000145:classification; D051381:Rats; D012107:Research Design; D018570:Risk Assessment; D018675:Toxicity Tests / Q000379:methods*
D004364:Pharmaceutical Preparations