FDA finalizes guidance on therapeutic protein biosimilars

The US Food and Drug Administration (FDA) has finalized a 2019 guidance on designing and evaluating comparative analytical studies used to compare a biosimilar to its reference product. The guidance replaces a 2015 guidance on the same topic.

On 8 September, FDA published the final guidance, which adds that the regulation of protein products has evolved with improvements in manufacturing processes, process controls, material control, and new testing capabilities (RELATED: FDA Replaces Withdrawn Biosimilar Guidance With New One on Quality-Related Considerations, Regulatory Focus, 21 May 2019).

“This final guidance describes the Agency’s recommendations on the design and evaluation of comparative analytical studies intended to support a demonstration that a proposed therapeutic protein product is biosimilar to a reference product licensed under section 351(a) of the PHS Act (42 U.S.C. 262(a)),” according to the Federal Register notice. “Additionally, this final guidance is intended to provide recommendations to sponsors on the scientific and technical information for the [chemistry, manufacturing, and controls (CMC)] portion of a marketing application for a proposed product submitted under section 351(k) of the PHS Act. Although the 351(k) pathway applies generally to biological products, this final guidance focuses on therapeutic protein products.”

The guidance lists factors to consider when performing comparative analytical assessments. The final version, however, removed the subsection on target binding and incorporated it into functional activity considerations. While FDA repeated that target binding methods such as surface plasmon resonance, enzyme-linked immunosorbent assay (ELISA), microcalorimetry, or classical Scatchard analysis can be used to understand the kinetics and thermodynamics of binding, the agency noted that the use of such methods should be discussed with regulators early on.

The draft guidance lumped together reference products and reference materials as a single factor. The final guidance, however, asks stakeholders to consider them separately. The draft guidance stated that sponsors could justify reliance on existing scientific knowledge of the reference product, but the final guidance also added that the FDA’s findings of safety, purity, and potency based on the FDA-approved labeling can also be used.

The main difference between the draft and final guidance is that the final guidance no longer includes a glossary of definitions. Previously, FDA provided definitions for terms such as biosimilar, chemically synthesized polypeptide, and protein. The final guidance also does not have a list of relevant guidances that sponsors should refer to in certain situations.

Another notable change in the final guidance is that FDA has removed references to animal studies and animal data. While the draft guidance stated that sponsors could use data and toxicity assessments from animal studies, the final draft states that sponsors can use toxicity assessments more broadly from studies outlined in the PHS Act. Similarly, when looking at comparative analytical data, the agency has taken out a reference to animal data.

Final guidance

FDA finalizes guidance on therapeutic protein biosimilars

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