Updated: Biosimilars in the US: Panel Discusses Tricky Balance of Building the Market With Necessary Precautions

Regulatory NewsRegulatory News | 20 June 2016 |  By 

Biosimilar experts, including the US Food and Drug Administration's (FDA) Dr. Leah Christl and biosimilar developer Coherus Biosciences' chief medical officer Dr. Barbara Finck, sat down on Monday at an Alliance for Health Reform event to discuss the challenges the US faces in developing a robust biosimilars market and also ways the US can avoid fear mongering and increase uptake.

Coherus' Finck, who was the only member of the panel with actual experience developing biosimilars and working with FDA to bring them to market, explained at the outset that although biosimilars are not like generic drugs (in that they are not exact replicas of their reference products), the “backbone of amino acids” between biosimilar and reference biologic have to be identical. And though there might be some minor variabilities between reference biologic and biosimilar, companies developing biosimilars for the US market “have to stay within a certain range of variability.”

And because of these variabilities, the generic-biosimilar comparison and parellel (though convenient) is actually inaccurate, and also unlike with generic drugs, Finck said, biosimilar companies have to spend significant amounts of money to obtain the reference biologics that are then characterized and reverse engineered and manufactured to create the biosimilar versions tested in clinical trials and later brought to market. Finck even said her company has gone so far as to obtain reference biologic samples from the EU, where they are cheaper, because so much biologic product has to be purchased in order to understand and characterize the product.

“If you know what you're doing, it's a bar that isn't too high,” Finck said of FDA's standards for biosimilarity, noting that industry has made enormous strides in recent years in analytical characterization technology and as in the more mature EU biosimilar market, where uptake has been mostly successful, biosimilars are generally safe.

In terms of interchangeability, which is the hottest topic for anyone who's following the US market (where two biosimilars are approved and one is currently marketed) closely, (as the US is the only country in the world that has established different statutory standards for when a product is considered a biosimilar and when it can be an interchangeable biosimilar, meaning patients can switch back and forth from the reference biologic to the biosimilar and pharmacies can make the switch without a physician's approval), Finck said she does not think FDA will require clinical trials for every approved indication (others have predicted a higher bar for clinical data).

And while FDA's Christl was not able to provide any sort of update on FDA's position on interchangeability (FDA has not released its guidance on interchangeability and Christl said it's expected later this year – though FDA also said last year it would be released in 2015), she did make clear that one of the biggest misconceptions is that biosimilars are approved at a lower standard when compared to biologics.

“The data elements will be different,” Christl said, referring to biosimilars and interchangeable biosimilars, noting that the statutory standard for interchangeability is an additional standard beyond biosimilarity but that does not mean one standard is higher or lower than the other.

As of 31 May, Christl also noted that there are 60 biosimilar products for 19 reference products in development, while six companies have publicly announced nine 351(k) applications (applications submitted for biosimilar approval).

And although none of the biosimilars currently approved in the US would have an impact on pharmacist substitution (biologics companies have waged an intense war at the state level, helping support and pass a number of bills that would require a biosimilar to be interchangeable in order for it to be switched by a pharmacist for a patient without a physician's prior authorization), Brian Lehman of the Ohio Public Employees Retirement System explained that he's working to create a system in his state in 2017 that would reduce copays and cost-sharing for patients, which would be a big help for those who need Enbrel (etanercept), biosimilar version is currently under FDA review, and Humira (adalimumab), which is also expected to have a biosimilar enter the US market in the near term.

The panel also discussed the ongoing fight over biosimilar names (and why the random four-letter suffix is or may not be necessary for tracking and prescribing biosimilars) and labels (and why some data may be necessary), though Christl said FDA cannot reveal any new information outside of what is posted in the Federal Register.

Biosimilars in the US: Next Steps

Editor's Note: Dr. Christl offered this clarification on the differing data elements between reference biologics and biosimilars: "The data packages differ between originator and biosimilar marketing applications, but the standard for approval of originator products under 351(a) and biosimilar products under 351(k) of the PHS Act is the same in that both must demonstrate that they are safe, pure, and potent for the approved conditions of use."

She also further clarified:

     351(a) BLA (originator, reference product) vs. 351(k) BLA (biosimilar or interchangeable product)

  • The objective of a biosimilar development program is to demonstrate through the totality-of-the-evidence that the proposed product is biosimilar to the reference product. 
  • The sponsor of the proposed biosimilar product does not have to independently establish the safety and effectiveness of its product; it establishes this through a demonstration of biosimilarity to the reference product. 
  • The sponsor of a proposed biological product that is demonstrated to be biosimilar to a reference product can rely on FDA's previous finding of safety, purity, and potency (i.e., safety and effectiveness) the reference product. The ability to rely on certain existing scientific knowledge about the reference product to support the safety, purity, and potency (i.e., safety and effectiveness) of the biosimilar product allows for a potentially shorter and less costly drug development program. This is what is meant by an abbreviated approval pathway.
  • The abbreviated approval pathway is not a lesser standard for approval.
  • The data packages differ between originator (351(a) BLA) and biosimilar (351(k) BLA) marketing applications, but the standard for approval of originator products under 351(a) and biosimilar products under 351(k) of the PHS Act is the same in that both must demonstrate that they are safe, pure, and potent for the approved conditions of use. 
  • The data package required for approval of a biosimilar product is quite extensive; it is the approval pathway that is abbreviated.  

    Biosimilar vs. Interchangeable Products

  • The statutory standard for interchangeability is an additional standard beyond biosimilarity.
  • The  statutory standard for interchangeability includes the biosimilarity standard, and includes additional standards.
  • The data packages will differ between marketing applications for biosimilar and interchangeable products based on the different statutory standards, just as they differ for other application types.
  • The standard for interchangeability is a different standard, but it is not “a higher standard” than biosimilarity in that the standard for biosimilarity is not a lesser or low standard.



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