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By Peijuan (Penny) Zhu, Shrinivas Savale, and Gillian Woollett

Clinical pharmacology studies are critical in demonstrating biosimilarity because they provide clinical pharmacokinetic/pharmacodynamic (PK/PD) similarity data to confirm biosimilarity. These studies address residual uncertainties after the analytical evaluation, add to the totality of evidence supporting biosimilarity, and guide the need for any subsequent clinical testing. In some cases, clinical pharmacology studies alone can be sufficient to address whether there are clinically meaningful differences between products.

The criticality of the clinical pharmacology studies is supported by key regulatory guidance on conducting clinical pharmacology studies. The Food and Drug Administration (FDA) published a draft guidance for industry on Clinical Pharmacology Data to Support a Demonstration of Biosimilarity to a Reference Product in May 2014, which was replaced by final guidance in December 2016. The final guidance links the quality of analytical data with adaptive clinical program design, and elaborates on the study design for acquisition of clinical pharmacology data as a part of the totality of evidence needed to demonstrate biosimilarity.

In addition, FDA’s draft guidance Considerations in Demonstrating Interchangeability with a Reference Product, one of the most anticipated guidances since 2014, was released in January 2017. This draft guidance discusses considerations for the design of a switching study necessary to achieve an FDA designation of interchangeability—a regulatory designation unique to the U.S. The clinical pharmacology components expected in the switching study are quite extensive, and after three switches, the primary endpoints of PK equivalence test are requested besides other descriptive endpoints of PK, PD, efficacy, safety, and immunogenicity.

The issuance of both guidances illustrates the importance of clinical pharmacology evaluations in the demonstration of both biosimilarity and interchangeability. The May AAPS Newsmagazine cover story, Clinical Pharmacology Studies to Support a Demonstration of Biosimilarity and Interchangeability, summarizes these clinical pharmacology considerations, raises a few points for discussion, and invites comments on the draft interchangeability guidance to encourage debate among industry peers. Read the full article today, and share your thoughts in the comments below.

Penny Zhu is the chair-elect of AAPS Biosimilars focus group and has 10 years of experience in drug development. She works as an associate director of Clinical Pharmacology at Sandoz Inc.
Shrinivas Savale is member of Clinical PK/PD Subcommittee of the AAPS Biosimilars focus group. With two decades of experience in drug development, he works as a consultant to CRO, pharma, and biopharma companies.
Gillian Woollett is senior vice president at Avalere and leads their FDA Practice. She is building a bridge for Avalere clients from the FDA space into the traditionally separate Centers for Medicare & Medicaid Services and health care policy/business world.