FDA Fosters Understanding about Approval Process for Biosimilars

By Leah Christl, PhD, Associate Director for Therapeutic Biologics and Director of the Therapeutic Biologics and Biosimilars Staff, Center for Drug Evaluation and Research, FDA

All FDA-approved biologics, including reference and biosimilar products, undergo a thorough evaluation so that patients can be assured of the efficacy, safety, and quality of these products. Biosimilars must meet the rigorous approval standards required by law. The goal of a biosimilar development program is to demonstrate biosimilarity between the proposed biosimilar product and the reference product, not to independently establish the safety, purity, and potency (safety and effectiveness) of the proposed product. State-of-the-art technology is used to compare the structure and function of the products, such as chemical identity and bioactivity, to demonstrate that the proposed biosimilar and the reference product are highly similar. A manufacturer must also demonstrate that its proposed biosimilar product has no clinically meaningful differences from the reference product in terms of safety and effectiveness. Generally, this is demonstrated through human pharmacokinetic and pharmacodynamic studies, an assessment of clinical immunogenicity, and, if needed, additional clinical studies. Any differences between the proposed biosimilar product and the reference product are carefully evaluated by the FDA to ensure the biosimilar meets the FDA’s approval standards.

The manufacturing of biosimilars is closely regulated by the FDA. The statute requires the applicant to demonstrate that the facility in which the biosimilar product is manufactured, processed, packed, or held meets standards designed to assure that the biosimilar product continues to be safe, pure, and potent. The manufacturing controls and facility requirements apply to biologics regardless of whether it is a reference product or a biosimilar.

Slight differences (i.e., acceptable within-product variations) are expected during the manufacturing process for biologics, regardless of whether the product is a biosimilar or a reference product. For both reference and biosimilar products, lot-to-lot differences (i.e., acceptable within-product variations) are carefully controlled and monitored.

The FDA recently launched an education campaign to help increase understanding of biosimilar and interchangeable products among healthcare professionals. An interchangeable product is expected to produce the same clinical result as the reference product in any given patient. In addition, for a product administered to a patient more than once, there must be no additional risk or reduced efficacy if a patient switches back and forth between an interchangeable product and a reference product, compared to using the reference product without switching. A product approved as an interchangeable product means that the FDA has concluded it may be substituted for the reference product without consulting the prescriber. It is important for healthcare providers to understand that the FDA undertakes a comprehensive evaluation to ensure that biosimilar and interchangeable products meet the respective rigorous standards for approval. Healthcare providers and patients can expect that there will be no clinically meaningful differences between taking a reference product and a biosimilar when these products are used as intended. As with other drug products, healthcare providers should review the prescribing information in the labeling for detailed information about the approved uses. All campaign materials and other information about biosimilar products can be found at www.fda.gov/biosimilars. ✦

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