Document Detail


Developmental toxicity testing of biopharmaceuticals in nonhuman primates: previous experience and future directions.
MedLine Citation:
PMID:  20926830     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Developmental toxicity studies for pharmaceutical safety testing are designed to evaluate potential adverse effects of drug treatment on pregnancy and on the developing embryo/fetus. Biopharmaceuticals present specific challenges for developmental toxicity testing because the pharmacology of these molecules, which are frequently human-specific proteins, is often restricted to humans and nonhuman primates (NHPs). For those species-restricted molecules, the only option for the evaluation of potential effects on development of the human biopharmaceutical is to use NHPs. This article reviews each of the stages of development in cynomolgus macaques (the most frequently used NHP) and the potential exposure of the embryo, fetus, and infant following administration of a biopharmaceutical during pregnancy and lactation. Because the purpose of the NHP developmental studies is to identify potential human risks, a comparison between macaque and human development and potential exposure has been made when possible. Understanding the potential exposure of the conceptus relative to critical periods in development is essential to designing a scientifically based study that adequately addresses human risks. Some options for NHP study designs, including the option of combining end points into a single study, and the pros and cons of each of the study options have been reviewed. Developmental studies for biopharmaceuticals in NHPs need to be optimally designed on a case-by-case basis taking into consideration the pharmacology of the molecule, the type of molecule (antibody or non-antibody), the potential exposure relative to the development of potential target organs, the clinical use, and the ethical considerations associated with the use of NHPs.
Authors:
Pauline L Martin; Gerhard F Weinbauer
Publication Detail:
Type:  Journal Article     Date:  2010-10-06
Journal Detail:
Title:  International journal of toxicology     Volume:  29     ISSN:  1092-874X     ISO Abbreviation:  Int. J. Toxicol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2011-03-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9708436     Medline TA:  Int J Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  552-68     Citation Subset:  IM    
Affiliation:
Centocor Research and Development, Inc, 145 King of Prussia Road, Radnor, PA 19087, USA Email: pmarti27@its.jnj.com.
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