Similarity by Design: FDA Withdraws Draft Guidance on Statistical Approaches

Recommendation

5-7 November 2024
Hamburg, Germany

GMP meets Development
GMP and FDA Compliance in Pharmaceutical Development and IMP Manufacturing

The U.S. Food and Drug Administration, FDA, recently withdrew its draft guidance “Statistical Approaches to Evaluate Analytical Similarity" issued in September 2017. According to FDA, the draft guidance was intended to provide advice for sponsors developing biosimilar products regarding the evaluation of analytical similarity between a proposed biosimilar product and a reference product. After considering public comments that the agency received about the draft guidance, the FDA determined it would withdraw the draft guidance. The comments addressed a range of issues that could impact the cost and efficiency of biosimilar development, including the number of reference product lots the draft guidance recommended developers to sample in their evaluation of high similarity and the statistical methods for this evaluation.

The FDA states that the agency intends to issue a future draft guidance that will reflect state-of-the-art techniques in the evaluation of analytical data to support demonstration that a proposed biosimilar product is highly similar to a reference product. The future draft guidance will address challenges faced by sponsors in designing studies that are intended to demonstrate that a proposed biosimilar product is highly similar to a reference product.  The future draft guidance also will focus on providing appropriate flexibility for sponsors without compromising FDA’s scientific standards for evaluating marketing applications for biosimilars.

"The FDA continues to encourage sponsors of proposed biosimilar products to discuss product development plans with the agency, including the evaluation of analytical data intended to support a demonstration that the proposed biosimilar product is highly similar to a reference product."  The Agency will communicate publicly when the new draft guidance is issued in relation to the evaluation of analytical data between a proposed biosimilar product and a reference product. In the meantime, sponsors can seek advice through formal meetings and other interactions with FDA, which are described in more detail in FDA’s draft guidance for industry, Formal Meetings Between the FDA and Sponsors or Applicants of BsUFA Products.

In addition, the European Medicines Agency EMA recently published a draft Reflection paper on statistical methodology for the comparative assessment of quality attributes in drug development. The deadline for comments was March 31, 2018. The proposed paper covers statistical aspects for the comparative assessment of quality attributes in the settings of pre- and post-manufacturing changes, biosimilar development as well as generics´ development. It is supposed to emphasize further discussion of realistic requirements to demonstrate 'Similarity by Design'.