FDA Replaces Withdrawn Biosimilar Guidance With New One on Quality-Related Considerations

Regulatory NewsRegulatory News | 21 May 2019 |  By 

A week after finalizing guidance on developing interchangeable biosimilars, the US Food and Drug Administration (FDA) has drafted guidance for biosimilar developers on the use of comparative analytical studies that can be used to assess whether a proposed product is biosimilar to a reference product.

The 28-page draft guidance revises a final guidance from 2015 on quality considerations for demonstrating biosimilarity and serves as a replacement for a 2017 draft guidance on statistical approaches to evaluating biosimilarity that was withdrawn last year after industry questions.

In addition to the focus on comparative analytical studies, the new draft also describes considerations and recommendations for sponsors on the scientific and technical information for the chemistry, manufacturing and controls (CMC) portion of a biosimilar marketing application.

“A scientifically sound characterization that provides a comprehensive understanding of the chemical, physical, and biological characteristics of the proposed product is essential to the design of the manufacturing process and to the conduct of development studies for all biological products,” FDA says.

The draft also includes a rundown of nine factors, with detailed guidance on each, that should be considered when performing a comparative analytical assessment:
  • Expression system;
  • Manufacturing process;
  • Physicochemical properties;
  • Functional activities;
  • Target binding;
  • Impurities;
  • Reference product and reference standards;
  • Finished drug product;
  • Stability.
Lot-to-Lot Variability

FDA recommends that biosimilar developers adequately characterize the lot-to-lot variability of the reference product and the proposed biosimilar.

“Considering the inherent heterogeneity present in protein products and the expected lot-to-lot variability stemming from manufacturing processes, the Agency recommends that a sponsor include at least 10 reference product lots (acquired over a time frame that spans expiration dates of several years), in the analytical assessment to ensure that the variability of the reference product is captured adequately,” the draft says.

FDA also recommends that a sponsor include “at least 6 to 10 lots of the proposed product in the comparative analytical assessment… These should include lots manufactured with the investigational- and commercial-scale processes, and may include validation lots, as well as product lots manufactured at different scales, including engineering lots.”

A sponsor intending to use a non-US-licensed comparator in certain studies “should provide comparative analytical data and analysis for all pairwise comparisons (i.e., U.S.-licensed product versus proposed biosimilar product, non-U.S.-licensed comparator product versus proposed biosimilar product, and U.S.-licensed product versus non U.S.-licensed comparator product),” FDA adds.

Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment and Other Quality-Related Considerations: Draft Guidance for Industry


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