Final Guidance from FDA on Clinical Pharmacology Data Needed to Support Biosimilars


By Kristin A. Connarn [1]

At the end of December 2016, the Food and Drug Administration (FDA) finalized the 2014 draft guidance explaining the requirements for clinical pharmacology data necessary to support a proposed biosimilar.  This is the fourth final guidance document released by the FDA so far, two other guidance documents still remain in draft form.

The Clinical Pharmacology guidance provides recommendations relating to clinical pharmacology studies that assess the presence or absence of clinically meaningful differences between the reference product and the proposed biosimilar.  The document is divided into four main sections: the role of clinical pharmacology studies in the demonstration of biosimilarity, critical considerations in the use of clinical pharmacology studies to support biosimilarity, developing clinical pharmacology data for supporting a demonstration of biosimilarity, and utility of simulation tools in study design and data analysis.  Subsections of the guidance focus on safety, immunogenicity, study design, pharmacokinetic (PK) and pharmacodynamics (PD) measures.

Clinical pharmacology studies are part of the industry’s approach to develop the data and information needed to support a demonstration of biosimilarity.  The outcomes of the studies can inform both the biosimilar company and the FDA on clinically meaningful differences between the biosimilar and the reference product, which can suggest additional investigation, and/or clinical studies, are needed.  Depending on the extent of the potential differences, further development may or may not continue.

Although the finalization of the guidance took nearly two years, the FDA has said that the “changes are for clarity, however, and are not substantive.”  (29 December 2016, Federal Register).  However, one difference worth noting is the rephrasing of the four possible outcomes and the terminology for the analytical comparison of a proposed biosimilar with its reference product.  The draft guidance included the categories: (1) not similar; (2) similar; (3) highly similar; and (4) highly similar with fingerprint-like similarity.  In comparison, the final guidance has rephrased these categories to: (1) insufficient analytical similarity; (2) analytical similarity with residual uncertainty; (3) tentative analytical similarity; and (4) fingerprint-like analytical similarity.  The previous terminology had faced criticism when the draft guidance was first released.

The industry is still awaiting guidance on the interchangeability of biosimilar products.


Nothing herein should be construed as legal advice or representation.

[1] Kristin A. Connarn is a partner in the Boston office of McDermott, Will & Emery.


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