Fragile Fraternity

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  • 08/14/2014

So much for regulatory fraternity …

PhRMA, BIO Open Fire On FDA's Biosimilars Guidance

By Jeff Overley

Law360, New York (August 13, 2014, 7:11 PM ET) -- Pharmaceutical Research and Manufacturers of America and the Biotechnology Industry Association are leading an attack by innovator drugmakers on the U.S. Food and Drug Administration’s most recent biosimilars guidance, saying in letters released Wednesday that it could let copycat products be sold without fully demonstrating safety and effectiveness.

In correspondence provided to Law360 following a Tuesday comment deadline, the trade groups each questioned biosimilars policies the FDA proposed in May regarding so-called clinical pharmacology data — relatively early research in small groups of human subjects.

PhRMA, for example, took issue with the FDA’s introduction of four categories of similarity — not similar, similar, highly similar, and highly similar with fingerprint-like similarity — saying that the “hierarchy is beyond the scope of the draft guidance.”

If the FDA insists on preserving the categories within the guidance, it should eliminate “vague and confusing” definitions that make it unclear how regulators will decide which classification to apply, PhRMA wrote.

BIO also voiced concerns with the four categories, specifically questioning the FDA’s statement that a product merely deemed similar — and therefore not comparable enough to qualify as a biosimilar — could be deemed highly similar if additional studies help to erase uncertainties.

That additional testing could “expose human subjects to an experimental therapy that had not met the statutory analytical threshold of ‘highly similar,’” BIO wrote.

Both organizations have members that are pursuing biosimilars, but they mainly focus on brand-name products, including branded biologics that stand to lose significant market share when biosimilars arrive on the scene. Any delays in finalizing FDA policies on biosimilars therefore may work to their advantage.

PhRMA’s letter also suggested that the guidance is murky with respect to when clinical pharmacology data is sufficient to establish biosimilarity. For example, at one point in the guidance, the FDA said that such data “may be sufficient to completely assess clinically meaningful differences between products,” PhRMA noted.

But the guidance also said that clinical pharmacology studies, “if done well,” can complement other data and guide future testing.

“Based on these passages, it is unclear to PhRMA when FDA believes that clinical pharmacology studies can constitute the full clinical assessment,” the organization wrote.

PhRMA and BIO also sounded alarms over the FDA’s approach to safety, specifically the issue of immunogenicity, which can refer to immune system responses that cause allergic reactions or alter a biologic’s effects. The FDA’s guidance said that such data may need to be supplemented by findings from post-approval studies, and both groups expressed concern. 

BIO, for example, wrote that “full evaluation of safety and immunogenicity should still be necessary before approval” and that the FDA should elaborate on the role of post-approval studies in demonstrating safety.

Also, BIO asked the FDA to better explain its suggestion that biosimilarity may be established by looking at a single, scientifically acceptable biomarker — say, blood pressure or cholesterol levels — or at a composite of multiple biomarkers that are "relevant."

“While this approach may have utility, it runs the risk of merely increasing the quantity of data without necessarily improving the quality and interpretability of the results,” BIO wrote.

Swiss drugmaker Roche AG — parent of U.S.-based Genentech Inc. and a member of BIO but not PhRMA — also submitted a letter seeking more clarity on the four categories of similarity and complaining that the guidance covers more than just clinical pharmacology data.

According to a public docket, two dozen letters have been submitted on the guidance, but as of Wednesday, the FDA had published only four of them. Those letters were from Roche, the United States Pharmacopeial Convention, an independent board established by Amgen Inc., and generics maker Apotex Inc., which posed five questions but little in the way of criticism.

Sandoz Inc., the first company to request FDA approval along the Affordable Care Act's biosimilar pathway, didn’t immediately respond to a request for a copy of any comments it submitted. Hospira Inc., which is also pursuing biosimilars, directed an inquiry to the Generic Pharmaceutical Association, which did not immediately have comments to share.


Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.

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