In March 2010, section 351(a) of the Public Health Service Act was amended to create an abbreviated pathway for the approval of biosimilars or interchangeable biologic products that were found to be highly similar to US Food and Drug Administration (FDA) licensed biologics.

Under the act’s definition, ‘biosimilarity’ means “the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components and… there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity and potency of the product.”

The long-awaited biosimilars guidance documents as well as two Q&A documents were issued with little fanfare on 9 February 2012. Although the guidance documents were just issued, according to media reports, FDA has held more than 20 pre-investigational new drug (pre-IND) meetings with sponsors on numerous proposed biosimilar products. FDA is encouraging early dialogue and is more than willing to provide guidance throughout development of biosimilar products.

FDA has clearly stated that assessment of demonstrated biosimilarity will include “totality of evidence” as part of the review process of the 351(k) application. The guidance makes it clear the agency has both the authority and the flexibility to determine animal and/or clinical testing requirements on a per-product basis upon assessment of the comparative analytical data. 

Some key topics discussed in these documents are a stepwise approach to the development of biosimilars; use of US-licensed reference products versus other comparators; nonclinical and clinical considerations; extrapolation of clinical data across indications; pediatric study requirements; interchangeability; postmarketing safety monitoring; and some additional highlights from the FDA guidance and Q&A documents.

Regulatory Focus, April 2012