FDA Draft: Label Must State Product Is Biosimilar

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By John T. Aquino

April 1 — Biosimilar product labels must include a statement that the product is a biosimilar and may rely on the data submitted for FDA approval by the originator biologic maker, according to a new FDA draft guidance document.

The draft guidance was released March 31 and is the subject of a notice set for April 4 Federal Register publication. Attorneys told Bloomberg BNA that the guidance document is relatively consistent with the labeling the Food and Drug Administration authorized for the first biosimilar approved under the Biologics Price Competition and Innovation Act in March 2015—Sandoz's Zarxio, a biosimilar of Amgen's Neuopogen.

“The big news about the draft guidance is that they got it out, and this alone will end some uncertainty for both the biosimilar applicant and the originator of the biologic, also known as the reference product sponsor (RPS),” said Siegmund (Sige) Gutman, chair of Proskauer’s life sciences patent practice.

He added, “In it, there is something for everyone.”

However, a few organizations, including the Patients for Biologics Safety and Access and the American College of Rheumatology, released statements indicating that the clinical trial data for the biosimilar should be included in the labeling and that the label should specify whether the supporting clinical data for each indication are derived from studies of the biosimilar or the reference biologic.

Biosimilarity Data

A biologic is a complex, large molecule, such as a monoclonal antibody or a cell signaling protein, that is different from the small molecules of chemically derived drugs. Generics of chemically derived drugs are identical to the brand product, while a product designed to resemble an FDA-approved biologic can only be approved by the FDA as biosimilar to the RPS with no clinically meaningful differences, and, on further FDA approval, as interchangeable without the approval of a physician.

The BPCIA, signed into law in 2010 as part of the Affordable Care Act, provides an abbreviated approval pathway for a biosimilar that partly relies on the data originally submitted to the FDA by the RPS for approval.

Thomas H. Wintner, an attorney with Mintz Levin, noted in an April 1 phone interview that reference product sponsors should be pleased that the draft guidance requires the label to have a clear statement that the product is a biosimilar, although some RPSs would have preferred that the label reference data from clinical studies the biosimilar applicant submitted to the FDA to establish biosimilarity.

“And from the biosimilar manufacturer's perspective, the FDA will still permit reliance in the labeling on the RPS's clinical studies, even if the biosimilar applicant's data show some differences with the RPS's, which wouldn't be surprising since FDA is approving the product as similar, not identical, to the reference product,” Wintner said.

Premier Inc., a performance improvement alliance of hospitals and other health-care providers, issued a statement March 31 praising the draft guidance, saying “it will help ensure that prescribers and pharmacists understand which drugs can be grouped and substituted for one another, avoiding the potential for error that would happen if biosimilars had wholly unique names that made no reference to the branded equivalent. Moreover, in avoiding distinguishable names for every biosimilar, we believe the FDA’s guidance will improve patient access and speed the uptake of these cost saving products.”

FDA Avoiding Confusion

In a “From Our Perspective” posting online, the FDA's Leah Christl addressed the agency's reasoning behind its decision to rely on the RPS's data in the labeling.

“While we recommend that biosimilar labeling include biosimilar product-specific data necessary to inform safe and effective use of the product, we generally do not recommend that comparative data supporting the demonstration of biosimilarity be included in biosimilar product labeling. We’ve taken this approach to avoid potential confusion or misinterpretation of the comparative data,” she said. Christl is associate director for therapeutic biologics and lead of the therapeutic biologics and biosimilars staff in the FDA's Office of New Drugs.

Christl wrote that, rather than essentially repeat the reference product’s demonstration of safety or effectiveness, comparative clinical studies are intended to demonstrate that there are no clinically meaningful differences between the proposed biosimilar product and the reference product.

“Indeed, comparative clinical studies in a biosimilar development program may use endpoints or study populations that are different from those used to support approval of the reference product. Due to the potential for differences in clinical study parameters, we think that including comparative clinical data in biosimilar product labeling would be confusing or even potentially misleading to health care providers,” Christl wrote.

Ultimately, Christl said, the comparative data are useful for the FDA to make a decision about biosimilarity, but aren't likely to be relevant to a provider’s prescribing considerations.

Looking Ahead

Wintner noted that the draft guidance says that clinical studies from the biosimilar applicant might need to be included on the label if needed to “inform safe and effective use.”

The draft guidance also touches on the “naming issue,” discussing when biosimilar sponsors should use their biosimilar’s name, the reference product’s proprietary name and the “core name” of the product—the part of the proper name that doesn't include the four-letter suffix proposed in the FDA’s draft guidance on biologics naming.

Proskauer's Gutman noted that the draft labeling guidance shouldn't be interpreted to be a definitive reflection of the FDA's position on the naming of biosimilars.

The draft guidance doesn't address AbbVie’s request that the labeling of a biosimilar note that it isn't approved for all the indications of the reference sponsor.

Wintner repeated that there were no real surprises in the draft guidance. “This will be more interesting when we have five or six biosimilar products on the market and we have two or three years in and we have some experience from when physicians actually prescribe biosimilars,” he said.

After the April 4 publication of the notice, there is a 60-day comment period on the guidance ending June 3. Comments may be submitted electronically on http://www.regulations.gov. The docket number is FDA-2016-D-0643.

To contact the reporter on this story: John T. Aquino in Washington at jaquino@bna.com

To contact the editor responsible for this story: Lee Barnes at lbarnes@bna.com

For More Information

The draft guidance is at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM493439.pdf.

Text of the Federal Register notice set for April 4 publication is at http://src.bna.com/dNr.