Comments Sent to FDA on Its Draft Biosimilars Guidance Mostly Conveyed Discontent, Insight & Intelligence™ : Apr 16, 2012

• Alex Philippidis

While FDA’s biosimilar draft guidance may have succeeded in conveying the agency’s expectations, it has also sparked resistance among some industry players. Comments received by FDA show that the proposal it released on February 9 has generated discontent over certain definitions as well as requirements.
FDA’s comment period on the draft document ended today. Stakeholders sent criticisms over the suggested protocols as well as several recommendations for change. The draft guidance, contained in three documents, represent FDA’s interpretation of the Biologics Price Competition and Innovation (BPCI) Act of 2009, which was part of President Barack Obama’s healthcare overhaul.
The BPCI created an abbreviated licensure pathway for biological products shown to be biosimilar to or interchangeable with an FDA-licensed biological reference product. FDA proposes to use a risk-based, totality-of-the-evidence approach.

What Makes a Biosimilar Similar?

In comments to FDA, two drug developers said that the agency should tighten its proposed biosimilarity standards. While commending FDA for “an excellent job drafting guidance on quality considerations for demonstrating biosimilarity to a reference product,” Genentech took issue with FDA’s proposed wording that manufacturers “should” thoroughly assess the analytical similarity of their biosimilars to their reference products, and  “should”  perform in-depth chemical, physical, and bioactivity comparisons with side-by-side analyses of “an appropriate number of lots of the proposed biosimilar product and the reference product.” FDA also suggested that “where available and appropriate,” manufacturers compare their products with the reference standard for specific suitable attributes such as potency.
The assessment of the analytical similarity of a biosimilar product and the robustness of these methods are fundamental requirements for a biosimilarity assessment, and use of the word “should” implies that it does not necessarily need to be done, Genentech noted. “Please replace ‘should’ with ‘is expected to’ or ‘needs to,’” Genentech stated in a letter transmitted to the agency by Earl Dye, director of technical regulatory policy and strategy.
Novo Nordisk urged FDA to define biosimilars as products that are as similar as scientifically possible to their reference products, at least through sharing the same amino acid sequence, without exception, as their reference products. The company cited FDA’s emphasis on the importance the 3-D structures of proteins play in their biological functions and the ability of post-translational modifications to alter the proteins’ functions.
“FDA should never permit biosimilar applications for products that cannot be adequately characterized,” Novo Nordisk stated in its letter, signed by James C. Shehan, Novo Nordisk’s corporate vp, legal, government, and quality affairs.

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