Nonclinical strategy considerations for safety pharmacology: evaluation of biopharmaceuticals.

INTRODUCTION: Biopharmaceuticals, such as monoclonal antibodies and recombinant peptides, are important therapeutics to treat human disease. Key features of biopharmaceuticals that make them innovative medicines are their clinical effectiveness, high specificity for their human target, long half-life and target coverage, and low risk for "off-target" pharmacology. AREAS COVERED: This paper describes nonclinical safety pharmacology assessment of biopharmaceuticals with an emphasis on special considerations needed for these agents. Insight is provided on various approaches to conduct safety pharmacology studies for such therapeutics, including appropriate integration into non-rodent toxicity studies. EXPERT OPINION: The safety pharmacology evaluation of biopharmaceuticals requires a science-based, case-by-case approach, as each biological modality will have unique pharmacological characteristics that influence the overall nonclinical safety assessment strategy. The integration of safety pharmacology endpoints into general (repeat-dose) toxicity studies is a rational paradigm for assessing potential changes in the cardiovascular, central nervous, and respiratory systems, but requires thoughtful and practical planning. In some cases, especially based on target-pharmacology concerns, dedicated and optimally designed safety pharmacology studies may be needed to assess the functional risk of a new biopharmaceutical. For example, cardiovascular telemetry studies may be needed to detect small changes in arterial blood pressure after acute and chronic exposure.