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By Robert G. Bell

Robert Bell

In May, the FDA released its new draft guidance Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product. The draft guidance addresses pharmacokinetic (PK) and pharmacodynamic (PD) comparisons of biosimilars to reference biologic products required as part of a stepwise approach to developing the data and information (totality of evidence) necessary to support biosimilarity. The clinical pharmacology assessment may be an important component of the scientific justification supporting extrapolation of clinical data to one or more additional conditions of use.  The guideline is not product specific.

The types of clinical pharmacology studies to be conducted will depend on the residual uncertainties about biosimilarity comparisons. These residual uncertainties may involve the test-and-reference analytical comparability exercise where the characterization could be described as “Highly similar with fingerprint-like similarity,” “Highly similar,” “Similar,” or “Not similar.” Several key concepts, such as exposure / response assessment, residual uncertainty evaluation, analytical comparability and quality, as well as bioanalysis and immunogenicity, are especially relevant to development of biosimilar products. The guideline states:

In certain circumstances, human PK and PD data that demonstrate similar exposure and response between a biosimilar and the reference product may be sufficient to completely assess clinically meaningful differences between products. This would be based on similar pharmacodynamics using a PD measure that reflects the mechanism of drug action in cases where the PD measure has a wide dynamic range over the range of drug concentrations achieved during the PK study. In such instances, a full evaluation of safety and immunogenicity would still be necessary, either before or after approval.

However, it appears in these certain circumstances an efficient and timely means of demonstrating biosimilarity and registration may be possible.

The guideline also describes the development of clinical pharmacology studies to support biosimilar development.  Biosimilars sponsors are encouraged to discuss the crucial aspects of their clinical pharmacology development plan with FDA in the early stages of the biosimilar development program. This includes study design, subject population, reference product choice, dose selection, administration, PK/PD measures, statistics, modeling and simulation.

Comments are due on the FDA’s draft clinical pharmacology guideline on August 12, 2014.  To submit your comments, please go to the Regulations.gov webpage for this guidance.

Robert G. Bell, Ph.D., is president and owner of Drug and Biotechnology Development LLC, a consultancy to the pharmaceutical industry and academia for biological, drug, and device development.