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Nonclinical Aspects of Biopharmaceutical Development: Discussion of Case Studies at a PhRMA-FDA Workshop

Eli Lilly & Co., Greenfield, Indiana, USA

K. Benson
K. Davis-Bruno

U.S. Food and Drug Administration, Silver Spring, Maryland, USA

M. Dempster

Glaxo Smith Kline, Ware, Hertfordshire, UK

G. L. Finch

Pfizer Inc., Groton, Connecticut, USA

P. Harlow

U.S. Food and Drug Administration, Silver Spring, Maryland, USA

H.G. Haggerty

Bristol Myers Squibb, East Syracuse, New York, USA

T. Hart

Glaxo Smith Kline, King of Prussia, Pennsylvania, USA

L. Kinter

AstraZeneca, Wilmington, Delaware, USA

J. K. Leighton

U.S. Food and Drug Administration, Silver Spring, Maryland, USA

J. McNulty

AstraZeneca, Waltham, Massachusetts, USA

L. Roskos

Medimmune Inc., Hayward, California

H. Saber

U.S. Food and Drug Administration, Silver Spring, Maryland, USA

A. Stauber

Eli Lilly & Co., Greenfield, Indiana, USA

M. Tabrizi

Medimmune Inc., Hayward, California

Correspondence: Address correspondence to Lorrene A. Buckley, PhD, Eli Lilly and Company, DC 1940, Lilly Corporate Center, Indianapolis, IN 46285, USA. E-mail:BuckleyLA{at}lilly.com

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.

Key Words: Biopharmaceuticals • Nonclinical • Regulatory • Safety Assessment

International Journal of Toxicology, Vol. 27, No. 4, 303-312 (2008)
DOI: 10.1080/10915810802367016


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