title: Alternative strategies for toxicity testing of species-specific biopharmaceuticals.
abstract: Although toxicology studies should always be conducted in pharmacologically relevant species, the specificity of many biopharmaceuticals can present challenges in identification of a relevant species. In certain cases, that is, when the clinical product is active only in humans or chimpanzees, or if the clinical candidate is active in other species but immunogenicity limits the ability to conduct a thorough safety assessment, alternative approaches to evaluating the safety of a biopharmaceutical must be considered. Alternative approaches, including animal models of disease, genetically modified mice, or use of surrogate molecules, may improve the predictive value of preclinical safety assessments of species-specific biopharmaceuticals, although many caveats associated with these models must be considered. Because of the many caveats that are discussed in this article, alternative approaches should only be used to evaluate safety when the clinical candidate cannot be readily tested in at least one relevant species to identify potential hazards.
authors: Toxicology, Amgen Inc, One Amgen Center Dr, MS 29-2-A, Thousand Oaks, CA 91320-1799, USA. jeanine.bussiere@amgen.com
authors: Jeanine L
authors: JL
authors: Bussiere
authors: Pauline
authors: P
authors: Martin
authors: Michelle
authors: M
authors: Horner
authors: Jessica
authors: J
authors: Couch
authors: Meghan
authors: M
authors: Flaherty
authors: Laura
authors: L
authors: Andrews
authors: Joseph
authors: J
authors: Beyer
authors: Christopher
authors: C
authors: Horvath
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000633:toxicity; D001702:Biopharmaceutics / Q000191:economics / Q000379:methods*; D015197:Carcinogenicity Tests; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000191:economics / Q000379:methods* / Q000592:standards; D004348:Drug Labeling; D015507:Drugs, Investigational / Q000633:toxicity*; D005260:Female; D055879:Gene Knock-In Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy; D011993:Recombinant Fusion Proteins / Q000633:toxicity; D013045:Species Specificity; D018675:Toxicity Tests / Q000191:economics / Q000379:methods* / Q000592:standards
chemical_list: D000911:Antibodies, Monoclonal; D015507:Drugs, Investigational; D011993:Recombinant Fusion Proteins