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Panelists Discuss Regulatory Perspective on Biosimilars


A trio of regulatory experts discuss the current standing of biosimilar policy in the United States and expectations going forward.

There were several firsts in 2021 for biosimilars, including the first interchangeable biosimilars and the first ophthalmology biosimilar, but under the surface an “identity crisis” has developed, said Eva Temkin, JD, a former regulator who moved recently to private law practice, in a panel discussion at the 2021 GRx+Biosims conference.

Temkin and Rachel Turow, JD, MPH, a private industry general counsel representing Teva Pharmaceuticals, agreed that many policy questions are coming to a head, such as labeling practices and defining the interchangeable designation. Interchangeable biosimilars are ones that pharmacists can dispense in place of reference brands without obtaining authorization from the prescribing physicians.

Looking from the outside in, Turow said that for regulators, this may be a time of intrigue and creative problem solving, but for the biosimilars industry, “it does seem to feel like you’re running around trying to put out many fires at once,” including legislative, regulatory, and patient and physician education problems.

The FDA is developing a regulatory science program with the goal of improving regulatory decision making and making it possible for stronger science-based recommendations in the development of applications under the Public Health Service Act 351(k) licensing process for biosimilars, said Alison Falb, JD, the sole regulatory panelist, who is counsel for the FDA's Office of Therapeutic Biologics and Biosimilars (OTBB).

The OTBB oversees regulatory policy for biosimilars, interchangeables, and other therapeutic biologic products.

Falb said a pilot program is scheduled for 2023 with the stated purpose of advancing the development of interchangeable biosimilars and improving the efficiency of biosimilar product development. The program will also help to determine what real-world evidence might be needed to establish the safety standards for interchangeable status. There will also be stakeholder meetings to review the progress made on these initiatives and determine future priorities.

"Skinny Labeling"

The practice of “skinny labeling” (labeling carve-outs) worries Turow, who heads up regulatory law and policy divisions for Teva.

Rachel Turow, JD, MPH; Teva Pharmaceuticals

I really hope we’ll see skinny labeling addressed, coming out of [GlaxoSmithKline v. Teva Pharmaceuticals USA, Inc], but I think the implications for biosimilars are really just as severe, if not more worrisome, in terms of the liability for induced patent infringement with a skinny label.

Labeling carve-outs involve marketing generics and biosimilars for a narrower range of medical indications than the brand products as a means of avoiding infringement of patents that concern only specific indications. The generic or biosimilar company may include only limited indications on its product label, which the FDA approves, but if the physician or patient assumes that the product is safe for all indications of the reference product and uses it for a patent-protected use, the question may arise whether the generic or biosimilar manufacturer “induced” the physician or patient to use the product for that indication.

GlaxoSmithKline (GSK) and Teva have battled over this issue in court, with GSK alleging induced infringement of Coreg (carvedilol) and Teva emerging as the victor. “I really hope we’ll see skinny labeling addressed, coming out of [GlaxoSmithKline v. Teva Pharmaceuticals USA, Inc], but I think the implications for biosimilars are really just as severe, if not more worrisome, in terms of the liability for induced patent infringement with a skinny label,” Turow said.

There are signs that federal policy makers are going to continue to support labeling carve-outs, said Temkin, a partner in the FDA and Life Sciences practice of King and Spalding and a former director of policy in the OTBB. She said this was clear from the text of a recent HHS report on drug competition and drug pricing. “Who knows what that will mean in practice and whether it will translate into congressional action, but it does seem to be a focus, and I think it’s an important thing to consider,” she said.

In September 2021, HHS issued its Comprehensive Plan for Addressing High Drug Prices to the White House, and in this, HHS emphasized that it considers the pathway for labeling carve-outs to be an important means of lowering costs for patients and the federal government via Medicare and Medicaid spending.

The FDA has also promised to provide more clarity on the handling of the interchangeable designation. Turow said there’s a lot of ground to cover in providing the desired level of detail for stakeholders in the biosimilar sphere. Aspects of the interchangeable designation requiring clarification range from basic comparability of the biosimilar and the reference product to labeling and any product application devices used. So far, 2 biosimilars have been issued the interchangeable designation in the United States.

“I do have my favorite interchangeability question,” Turow said, “which is if biosimilar A is interchangeable to the reference product and biosimilar B is interchangeable to the reference product, are they interchangeable with each other? And I don’t think the FDA has answered that question.”

Turow said she’s encouraged that pharmacy benefit managers recently have been moving interchangeable biosimilars onto their preferred formularies, but she said that, in the health care community, there’s still a lot of basic education required about biosimilars to generate more confidence in their use.

BsUFA Reauthorization

Under the Biosimilar User Fee Act (BsUFA) reauthorization for 2023 to 2027, the FDA spells out product developer fees and goals for developing the biosimilar approvals process, and the reauthorized plan includes addressing product labeling, interchangeability, and advertising for biosimilars, Falb said. With regard to the interchangeable designation for biosimilars, this includes paying attention to postapproval manufacturing changes to products and addressing differences between drug application products. “I think it’s definitely something we consider a high priority area for guidance,” she said.

As for labeling differences between biosimilars and interchangeable biosimilars, Falb said, the FDA has previously stated that “the principles from the biosimilar labeling guidance would also apply to interchangeable biosimilar labeling,” although the interchangeable designation is somewhat different from the biosimilar definition and those standards also are relevant to how these agents should be regarded, Falb said.

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