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Regulatory Focus™ > News Articles > FDA Likely to Require Substantial Clinical Data for Interchangeable Biosimilars, Lawyers Say

FDA Likely to Require Substantial Clinical Data for Interchangeable Biosimilars, Lawyers Say

Posted 12 January 2016 | By Zachary Brennan 

FDA Likely to Require Substantial Clinical Data for Interchangeable Biosimilars, Lawyers Say

The US Food and Drug Administration (FDA) is “almost certain” to require clinical data in order for companies to demonstrate interchangeability between a biosimilar and its reference product, though the question of how much data will be required is major factor in determining how quickly the US biosimilars market will take off, according to a new report from the law firm Goodwin Procter.

The Biologics Price Competition and Innovation Act(BPCIA) of 2010 established the US market for biosimilars, which, like the name indicates, means the products are similar but not identical -- like small molecule generics -- in efficacy and safety when compared to their biologic reference products. And although the BPCIA makes no mention of clinical studies for biosimilars, “comments made by FDA have indicated that this is a very real possibility,” according to the report.

If clinical trials are required for a biosimilar to be considered interchangeable, that bar may essentially limit which biosimilars can be switched over from their reference products automatically.

As far as what kind of clinical trial will be needed for a biosimilar manufacturer to successfully have a shot at automatic substitution, Rob Cerwinski, a partner in Goodwin Procter's IP Litigation Group, told Focus: “All we know is that it’ll be a high-powered study."

FDA has yet to issue its guidance on how industry should establish interchangeability, though it’s expected to be released in 2016 after the agency failed to meet its goal of publishing the document last year.

“Indeed, how to demonstrate interchangeability remains very much unclear,” the report says.

In draft guidance from 2015, FDA stated that, “It would be difficult as a scientific matter for a prospective biosimilar applicant to establish interchangeability in an original 351(k) application given the statutory standard for interchangeability and the sequential nature of that assessment. FDA is continuing to consider the type of information sufficient to enable FDA to determine that a biological product is interchangeable with the reference product.”

And though no companies have publicly stated that they would specifically try to market an interchangeable biosimilar, Cerwinski remains optimistic that there will be some looking to differentiate their businesses with interchangeability.

“Once we see some of that science worked out and it doesn’t blow the economics out of the water, [interchangeability] could very well drive biosimilar uptake in US,” he added, particularly as so many states have already established legislation requiring a biosimilar to be interchangeable for automatic substitution at the pharmacy level to occur.

Elaine Blais, head of the litigation department at Goodwin’s Boston office, said biopharma companies have been lobbying state legislatures “like crazy” to make automatic substitution difficult and to keep their market share higher. “I can’t imagine the money being spent on that.”

As far as what to expect in the near future, six biosimilar applications are currently pending FDA review:

  • Celltrion’s biosimilar of infliximab, which is based on the reference product Remicade, a monoclonal antibody to treat autoimmune disorders such as rheumatoid arthritis. In February 2015, FDA postponed an advisory committee meeting for Celltrion’s biosimilar version of infliximab because of pending information requests to the company. A future date has yet to be announced.
  • Two biosimilar applications relating to Amgen’s Neulasta (pegfilgrastim) from Apotex and Sandoz.
  • Apotex’s biosimilar based on Amgen’s Neupogen, which would be the second biosimilar for this drug (the first was the only biosimilar approved by FDA so far, Sandoz’s Zarxio (filgrastim-sndz).
  • Sandoz’s 262(k) application for a biosimilar version of etanercept, which is based on Amgen’s Enbrel.
  • And Amgen’s application based on AbbVie's reference product Humira (adalimumab).

In addition to the interchangeability guidance, FDA also plans to publish three additional draft guidance documents in the near future, including, “Labeling for Biosimilar Biological Products,” and “Statistical Approaches to Evaluation of Analytical Similarity Data to Support a Demonstration of Biosimilarity.”

Goodwin Procter Guidebook on Biosimilars Regulatory, IP Issues


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