FDA publishes more biosimilar labeling advice after pharma voices its concerns

The FDA has released further draft guidelines on how biopharma should label their new copycat biologics in what has been described as a "positive for the biosimilars industry," but problems over interchangeability remain.

The new 15-page document comes just over a year after the first biosimilar was approved by the U.S. regulator, which hit the green light on Zarxio (filgrastim-sndz) from Novartis' ($NVS) Sandoz unit, a biosimilar of Amgen's ($AMGN) chemotherapy side effects drug Neupogen (filgrastim).

But the labeling of the drug irked some pharma giants facing biosimilar competition. They have since asked the FDA to move away from the type of labeling format it had used for Zarxio, as they argued its labeling was generally similar to how the agency writes up labels for regular generics (i.e., similar to the brand). 

Some companies were so annoyed that AbbVie ($ABBV) argued in a citizen petition against the FDA last year that biosimilars should not be labeled like generic drugs. The company stands to lose out as biosimilar rivals loom for its megablockbuster $13 billion-year Humira franchise.

What pharma wants is for the regulator to allow a description of the clinical data used by the biosimilar for approval purposes, and to also describe differences versus the brand's data, in order to make a distinction.

In this new draft guidance--which is subject to change--the FDA will rely heavily on their reference products' labels, and will typically not use trial data.

In the guidance document, the FDA says that the data generated by the biosimilar isn't something it generally intends to include in the product label, but may be included "when necessary to inform safe and effective use."

The document said: "Information and data from a clinical study of a proposed biosimilar product should be described in its labeling only when necessary to inform safe and effective use by a healthcare practitioner.

"As a general matter, it is FDA's view that biosimilar product labeling should not include a description of these data, given that a clinical study supporting the licensure of the biosimilar product generally would not be designed to independently demonstrate the safety and efficacy of the product, but rather to support a demonstration that there are no clinically meaningful differences between the proposed biosimilar product and the reference product for the approved."

But the FDA has attempted to be sensitive to pharma's request, and goes on to say that: "However, I want to point out that these comparative data generally will be available to the public. Healthcare providers and others who want to delve more deeply into the product-specific data supporting a demonstration of biosimilarity, including the comparative clinical data, may find this information in FDA's product reviews, on our [email protected] website."

The guidance also states that a label should be written in a manner that does not imply that the biosimilar product is approved for a reference product indication or use that has not been approved for the biosimilar product.  

Umer Raffat, a senior analyst at Evercore ISI, said issues still remain as the guidance document "does not address exactly how to determine interchangeability--it specifically says that this issue will be addressed in the future."

This is a major problem, as with an interchangeability designation, the biosimilar can be substituted for the reference product without the approval of a doctor. Much of the issue around interchangeability is how a patient would perform if switched between the reference product and biosimilar.

Mizuho Securities analyst Eric Criscuolo said in a research note that this latest guidance "is a positive" for biosimilar manufacturers. He explained: "In the guidance, the FDA recommends that the biosimilar product labeling should incorporate the reference product labeling, including its clinical efficacy and safety data. Basically, the biosimilar gets to use the clinical trial data that supported the reference product's approval.

"The guidance would also allow biosimilar labels to specifically say that the product is biosimilar to the reference product (along with a definition of what that means). In addition, the guidance makes recommendations for how to identify the biosimilar and reference products throughout the drug label- for example, when to use just the biosimilar product name (i.e. Zarxio or filgrastim-sndz); just the reference product name (i.e. NEUPOGEN); just the core name (i.e. filgrastim), and when to use more than one product name."

The Biosimilars Forum--the U.S. nonprofit organization--said it was "pleased that the FDA is continuing to provide guidance for this developing industry; … the Forum will carefully review the guidance and will submit comments to the FDA within the 60-day comment period."

Last year's approval for Zarxio has opened the floodgates for more biosimilars as companies line up to take on giants such as Lantus and Humira, but both legal challenges/patent disputes and a slowness from the FDA to update its guidance has caused frustration for the biosimilar industry.

Defining biosimilarity is among many outstanding questions in the FDA's years-long effort to figure out how it will approve copies of biologic medicines. This puts it around a decade behind Europe, which started issuing approvals for biosimilars back in 2006.  

- check out the FDA's guidance (PDF)
- see RAPS take