Biologics

FDA Aims to Cut Comparative Efficacy Studies for Biosimilars

David McFarland

— 2 min read
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FDA is proposing a major shift in how biosimilars are evaluated, signaling that many products may no longer need traditional comparative clinical efficacy studies (CES) to demonstrate biosimilarity. A new draft guidance, Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies, reflects the agency’s growing confidence in advanced analytical technologies and pharmacokinetic data.

The move, anticipated for some time, gained considerable attention last month after FDA granted its first-ever waiver of a CES for a monoclonal antibody biosimilar (see story). The upcoming submission from University of Illinois adjunct professor and founder of several biopharmaceutical ventures Sarfaraz K. Niazi will seek approval for a biosimilar version of Johnson & Johnson’s Stelara (ustekinumab).

CESs have long been a costly and time-consuming part of biosimilar development, though critics have argued they add little value in demonstrating equivalence when analytical and immunogenicity testing already confirm similarity to reference products. Niazi has spent years petitioning FDA and publishing peer-reviewed articles advocating for the elimination of CESs. According to Niazi, removing the requirement could cut biosimilar development costs by more than 90% and shorten approval timelines by 70%, lowering barriers for smaller companies to enter the market.

Under the Public Health Service Act, biosimilar applications must include clinical data sufficient to demonstrate safety, purity and potency. Historically, that has included at least one CES. But FDA now says its scientific understanding has evolved.

According to the draft guidance, comparative analytical assessments (CAA) — which include sophisticated structural and functional assays — are now considered more sensitive than CES in detecting clinically meaningful differences between a biosimilar and its reference product. Clinical trials, by contrast, often lack sensitivity due to factors like dosing at therapeutic plateaus and variability within patient populations.

FDA’s draft guidance recommends a “streamlined approach” in many cases: if a CAA shows high similarity and pharmacokinetic and immunogenicity data confirm no meaningful clinical differences, a CES may not be required. The agency says it will evaluate the totality of evidence in each biologics license application. The draft guidance identifies several conditions where this reduced clinical burden is most likely to apply:

  • Both products are highly purified and well-characterized, including being derived from clonal cell lines
  • • Key quality attributes that correlate with clinical outcomes are well understood and measurable
  • • A human pharmacokinetic similarity study is feasible and clinically relevant

Still, FDA stresses CES will remain necessary in some circumstances — particularly for locally administered products, such as intravitreal therapies, where pharmacokinetic comparisons are not meaningful. The agency also notes that in some cases, other clinical endpoints beyond efficacy may be needed.

Additionally, the agency recommends that sponsors engage early if uncertainty remains. The draft guidance is open for public comment.

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