The Current State of the US Biosimilar Regulatory Pathway

The FDA has seen a steady increase in biosimilar development programs since the passage of the Biologics Price Competition and Innovation Act of 2009 (BPCIA), with 9 biosimilars approved by the end of 2017 and 68 active biosimilar programs in development. Writing in a Perspectives article published in the January 2018 issue of Clinical Pharmacology & Therapeutics, Michele K. Dougherty, PhD, and colleagues at the FDA predict the success of the agency’s biosimilars program and anticipate that as biosimilar development programs continue to mature, there will be an influx of biosimilar approval applications filed at the agency, and that the FDA and the biopharmaceutical industry will continue to build on the lessons learned from early biosimilar development programs. The authors believe the future will bring greater patient access to safe, effective, and presumably more affordable biological products though the approval of more biosimilar products.

Dougherty and her coauthors explain the history of the US biosimilar approval pathway as laid out by the BPCIA, which requires that a proposed biosimilar product demonstrate, through a stepwise development approach, that is has the same strength, route of administration, and dosage form as the FDA-approved reference biologic, and that it uses the same mechanism of action (MOA) for the proposed conditions of use that the reference product previously showed during its approval process. The authors stress that the BPCIA abbreviated licensing pathway for biosimilars is not a lower approval standard, but rather allows for reliance on the FDA’s previous finding of safety and effectiveness for the reference product, promoting a shorter and less costly development program for biosimilars. Biosimilar sponsors provide extensive data from analytic studies, nonclinical studies, and clinical studies, they note, but “the goal of the biosimilar program is not to re-establish the safety and efficacy of the product but rather to demonstrate that the biologic product is biosimilar to the reference product.”

They explain that the “totality of the data” provides evidence of biosimilarity and why no single study is deemed pivotal in the biosimilar approval process. The totality of data and information submitted in the biologic licensing application (BLA) must support the demonstration of biosimilarity; extrapolation of data for different indications must be scientifically justified, and factors considered that include MOA in each indication sought, they note. Concerns about pharmacokinetics, immunogenicity, and toxicity in different patient populations and uses are addressed in this process. The authors conclude that the biosimilar licensing pathway results in biosimilar products that patients and physicians can rely upon as far as safety and effectiveness in the same way that they would for the reference product in each condition of use for which the biosimilar product is approved.

Finally, Dougherty and colleagues note that the FDA aims to increase transparency in the review process for biosimilars, allowing for enhanced communication during the review cycle to achieve more first-cycle approvals. Labeling for biosimilars is an area the FDA and the industry are addressing through guidance and implementation during licensure of the first biosimilar products, as well as interchangeability with the reference product.