Interchangeability of Biosimilars: What Level of Clinical Evidence is Needed to Support the Interchangeability Designati
- PDF / 749,858 Bytes
- 10 Pages / 595.276 x 790.866 pts Page_size
- 71 Downloads / 197 Views
REVIEW ARTICLE
Interchangeability of Biosimilars: What Level of Clinical Evidence is Needed to Support the Interchangeability Designation in the United States? Daniel F. Alvarez1 · Gertjan Wolbink2 · Carol Cronenberger3 · John Orazem4 · Jonathan Kay5,6
© The Author(s) 2020
Abstract A biosimilar is a biologic drug that is “highly similar to a reference (originator) product, with no clinically meaningful differences between the two products in safety, purity, and potency”. Regulatory approval of a biosimilar is based on analytical, structural, and functional comparisons with the reference product, comparative nonclinical (in vivo) studies, clinical pharmacokinetics and/or pharmacodynamics, and immunogenicity. In addition, comparative clinical efficacy and safety assessments are usually conducted and, taken together, comprise the “totality of the evidence” supporting biosimilarity. For a biosimilar to meet the additional designation of interchangeability in the United States (US), the applicant must demonstrate that the biological drug can be expected to produce the “same clinical result as the reference product in any given patient” and “if the biological drug is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between the use of the biological drug and the reference product is no greater than the risk of using the reference product without such alternation or switch”. The challenges faced in conducting clinical studies to support a designation of interchangeability, as defined in the final interchangeability guidance from the US Food and Drug Administration, are considered. Potential alternative approaches to generating adequate and sufficient clinical data to support a designation of interchangeability are also presented.
1 Introduction A biosimilar is a biologic drug that is “highly similar to a reference (originator) product, and for which there are no clinically meaningful differences between the two products in safety, purity, and potency” [1]. The development and approval of a biosimilar is based on extensive * Daniel F. Alvarez [email protected] 1
Inflammation and Immunology, Pfizer Inc, 500 Arcola Rd, Collegeville, PA 19426, USA
2
University of Amsterdam, Amsterdam, The Netherlands
3
Clinical Pharmacology, Pfizer Inc, Collegeville, PA, USA
4
Global Biostatistics and Data Management, Pfizer Inc, New York, NY, USA
5
Departments of Medicine and of Population and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, MA, USA
6
Department of Medicine, UMass Memorial Medical Center, Worcester, MA, USA
Key Points In the United States, an approved biosimilar can be designated as “interchangeable.” The United States Food and Drug Administration expects clinical data to support a demonstration of interchangeability. Clinical studies that support interchangeability should be designed primarily to evaluate if clinical performance is altered by multiple switching between a refer
Data Loading...
