Industry concerned over hurdles in FDA’s biosimilars manufacturing changes guidance

Biosimilars trade groups and manufacturers have expressed concern about what they say are “unnecessary hurdles” present in the US Food and Drug Administration’s (FDA) recent draft guidance on biosimilar postapproval manufacturing changes released in July.

The guidance, Postapproval Manufacturing Changes to Biosimilar and Interchangeable Biosimilar Products Questions and Answers Guidance for Industry, details how manufacturers should report postapproval production changes for licensed biosimilar and interchangeable products.

The draft guidance addresses “commonly asked questions” on postapproval manufacturing changes and fulfills an FDA commitment made in the 2022 reauthorization of the Biosimilar User Fee Amendments (BsUFA III).

In its comments to the agency, Samsung Bioepis took aim at the existence of the guidance itself, arguing such an additional document creates new risks for biosimilar developers.

“We are concerned by having a separate guidance unique to the US for post-approval manufacturing changes to biosimilar and interchangeable biosimilar products,” the company said.

“It is not needed and, worse,” Samsung Bioepis said, “it could be used to imply that there are additional or merely different risks for 351(k) products compared to other biologics already licensed under 351(a)… biosimilar and interchangeable biosimilar products are already biologics, just like their reference products, and all issues pertaining to quality, safety and efficacy (safety, purity and potency) of biologics already must and do apply.”

The Biosimilars Forum took a more amenable stance on the guidance, but echoed Samsun Bioepis’ call for it to apply to not only all 351(k) products, but all biologics, regardless of approval pathway. The group also raised questions about the reference materials needed for the comparability exercise detailed in the guidance. “As written, the Forum believes this section requires important edits,” the group wrote, calling for FDA to revise the guidance to specify that if an applicant submits sufficient data to show that the change will not adversely impact quality, safety, or efficacy, the agency will “generally consider the data adequate to support the change without the inclusion of reference materials beyond the in-house reference material in the comparability exercise.”

“There are very real risks created by two separate guidances that attempt to address the same regulatory issues as they could be amended differently over time and get out of sync,” Samsung Bioepis continued, noting that the International Council for Harmonisation’s (ICH) Q5E guideline “is already being used in practice for biosimilar and interchangeable biosimilar products in the same manner as it is being applied to originator biologics and there is no need for this to change.”

Though the Campaign for Sustainable Rx Pricing (CSRxP) welcomed the draft guidance, the nonpartisan coalition suggested that “the FDA revise the draft guidance to clarify that a pre- and post-change comparability demonstration needs to only reference the biosimilar undergoing the manufacturing change – and not also the reference biologic.”

“The draft guidance in certain cases,” warned CSRxP, “appears to suggest that the post-manufacturing change comparability demonstration would have to apply to both the reference biologic and the biosimilar undergoing the manufacturing change.” This requirement would be “unnecessary and costly” as demonstration to the pre-change biosimilar “should be sufficient to continue demonstrating biosimilarity or interchangeability to the reference biologic,” argued the advocacy group.

Similarly, AHIP wrote the group encourages “the FDA to revise its draft guidance to clarify that a pre- and post-change comparability demonstration need only reference the biosimilar undergoing the manufacturing change.”

“In some portions of the draft guidance,” AHIP noted, “the FDA suggests that a post-change biosimilar may need to demonstrate biosimilarity or interchangeability to the reference biologic.” “We are concerned that this approach may create unnecessary hurdles to the availability of lower cost biosimilars,” continued AHIP, “as a demonstration of post-manufacturing change comparability to the pre change biosimilar should be sufficient to continue demonstrating biosimilarity or interchangeability to the reference biologic.”

On the other hand, in its published comments, the Pharmaceutical Research and Manufacturers of America (PhRMA) said it “supports FDA’s position that analytical comparability data includes historical analytical data.”

Such historical data, said PhRMA, includes the “results from biosimilar or interchangeable biosimilar lots used in the comparative analytical assessment (“CAA”), lots used in the clinical development of the biosimilar or the interchangeable biosimilar, lots used to support process consistency, and commercial materials manufactured after approval, as applicable.”

But the group did request a clarifying revision in the agency’s discussion of product quality data.

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Industry concerned over hurdles in FDA’s biosimilars manufacturing changes guidance

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