title: Nonclinical aspects of biopharmaceutical development: discussion of case studies at a PhRMA-FDA workshop.
abstract: Robust assessments of the nonclinical safety profile of biopharmaceuticals are best developed on a scientifically justified, case-by-case basis, with consideration of the therapeutic molecule, molecular target, and differences/similarities between nonclinical species and humans (ICH S6). Significant experience has been gained in the 10 years ensuing since publication of the ICH S6 guidance. In a PhRMA-FDA-sponsored workshop, "Nonclinical Aspects of Biopharmaceutical Development," industry and US regulatory representatives engaged in exploration of current scientific and regulatory issues relating to the nonclinical development of biopharmaceuticals in order to share scientific learning and experience and to work towards establishing consistency in application of general principles and approaches. The proceedings and discussions of this workshop confirm general alignment of strategy and tactics in development of biopharmaceuticals with regard to such areas as species selection, selection of high doses in toxicology studies, selection of clinical doses, the conduct of developmental and reproductive toxicity (DART) studies, and assessment of carcinogenic potential. However, several important aspects, including, for example, appropriate use of homologues, nonhuman primates, and/or in vitro models in the assessment of risk for potential developmental and carcinogenic effects, were identified as requiring further scientific exploration and discussion.
authors.affiliation: Eli Lilly and Company, DC 1940, Lilly Corporate Center, Indianapolis, IN 46285, USA. BuckleyLA@lilly.com
authors.forename: L A
authors.initials: LA
authors.lastname: Buckley
authors.forename: K
authors.initials: K
authors.lastname: Benson
authors.forename: K
authors.initials: K
authors.lastname: Davis-Bruno
authors.forename: M
authors.initials: M
authors.lastname: Dempster
authors.forename: G L
authors.initials: GL
authors.lastname: Finch
authors.forename: P
authors.initials: P
authors.lastname: Harlow
authors.forename: H G
authors.initials: HG
authors.lastname: Haggerty
authors.forename: T
authors.initials: T
authors.lastname: Hart
authors.forename: L
authors.initials: L
authors.lastname: Kinter
authors.forename: J K
authors.initials: JK
authors.lastname: Leighton
authors.forename: J
authors.initials: J
authors.lastname: McNulty
authors.forename: L
authors.initials: L
authors.lastname: Roskos
authors.forename: H
authors.initials: H
authors.lastname: Saber
authors.forename: A
authors.initials: A
authors.lastname: Stauber
authors.forename: M
authors.initials: M
authors.lastname: Tabrizi
mesh_terms: D000818:Animals; D001685:Biological Factors; D002626:Chemistry, Pharmaceutical; D006801:Humans; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D001685:Biological Factors