FDA Moving Biosimilar Substitution Guidance Forward Robustly

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By John T. Aquino

The FDA is committed to moving its biosimilar interchangeability draft guidance without delay through the regulatory process, an agency official told Bloomberg BNA April 6.

Leah Christl, associate director for therapeutic biologics for the Food and Drug Administration’s Center for Drug Evaluation and Research, described at a conference session the agency’s proposed methods to determine whether a biosimilar, a highly similar, less expensive version of an FDA-approved biologic drug, can be designated interchangeable. Interchangeable means a pharmacist could switch a patient to the biosimilar without a doctor’s approval.

Biopharma companies like Sandoz Inc. and Amgen Inc. are closely watching the FDA’s progress toward a final guidance on the interchangeability designation, which is likely to generate higher revenues because patients can be switched more easily to the substitute drug.

Christl acknowledged to Bloomberg BNA that the agency extended the deadline for comments on the draft guidance 60 days to May 19. “But our reviewing the draft guidance comments and moving toward the completion of a final guidance will be robust. We only extended the deadline because those wishing to make comments asked us for more time. We have staff who have been designated to review the comments and they are excitedly waiting to do so.”

Christl spoke at the 2nd Annual National Policy and Advocacy Summit on Biologics and Biosimilars, sponsored by the Alliance for Patient Access.

Totality-of-Evidence Standard

The Biologics Price Competition and Innovation Act provides an abbreviated pathway for FDA approval of a biosimilar. The FDA has approved four biosimilars since the BPCIA became effective in 2010, but none so far has gotten the interchangeable designation.

Christl stressed that the abbreviated approval pathway for biosimilars isn’t a lesser standard or a lesser pathway, as some have suggested. “FDA has to be convinced the biosimilar product is safe and effective,” she said. “The pathway is shorter and less costly because of the applicant’s ability to have a less expensive development by relying on the [original biologic’s] data.”

The major components of the draft interchangeability guidance are:

  •  the FDA would expect the biosimilar to meet standards for all the original biologic product’s conditions of use, whether the applicant is seeking approval for those conditions or not;
  •  the FDA would use a totality-of-evidence standard to evaluate interchangeability and apply a step-wise approach to generate data on any residual uncertainty;
  •  overall, the agency would use a risk-based approach to interchangeability that considers residual uncertainty, evaluating each product on a case-by-case basis;
  •  the product’s structural and functional complexity may influence the data needed; and
  •  a switching study or studies should be submitted showing the effects of switching a patient from a biologic to its biosimilar.
“The switching studies should be product-specific and consider the scenario where there is the most clinical concern for patients,” Christl said.

Switching Studies

Dr. David Charles, chief medical officer at Vanderbilt University and AFPA chairman, elaborated on the concept of switching during a separate conference panel.

“What we’re talking about is not a one-time, yes or no decision but a series of biologics for the treatment of chronic diseases, some of which may be biosimilars. Patients may be prescribed a number of different biologics and biosimilars in their lifetime, and it is our job to see that they are all safe and effective.”

He noted the Nor-Switch study that showed no lesser effects from switching from Johnson & Johnson’s biologic Remicade (inflikimab) for the treatment of rheumatoid arthritis and Crohn’s disease to Hospira’s Remsima and Celltrion’s Inflectra, both biosimilars of Remicade. “While that was encouraging, the study was based on one switch. There are concerns that policymakers will rely on this data, thinking that it can be applied to the multiple switches from biologic to biologic chronic disease patients will experience,” Charles said.

Naming, Pricing, Timing

Panelist Greg Schimizzi, a rheumatologist, said it would be good to get a definition from the FDA of what is substitutable, noting that the agency has avoided using the word. He also criticized the FDA’s plan for naming biologics and biosimilars with a “nonsense” suffix. He noted that a recent survey of physicians by the Biologics Prescribers Collaborative, a project of the AFPA, showed an overwhelming preference for a meaningful name for biosimilars.

Sen. Bill Cassidy (R-La.), a member of the Senate Committee on Health, Education, Labor, and Pensions and a physician, noted the positive changes biologics and biosimilars have brought to medicine and the challenges that remain. “What if we find a treatment for Alzheimer’s, but it costs $100,000 a year, thus limiting who will be able to receive it? The challenge before us is how do we reward innovation without bankrupting our country.”

Steve Grossman, an FDA consultant, said during the panel that one of the mistakes some have made is assuming that the FDA process for addressing biosimilars would be accomplished quickly. “It’s a new thing, it’s an important thing and the FDA wants to get it right.”

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

To contact the editor responsible for this story: Randy Kubetin at RKubetin@bna.com

For More Information

The AFPA's educational video on interchangeability is at https://www.youtube.com/watch?v=HiKEY1TPvRQ&t=48s.

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