Biosimilars Regulation Highlighted by FDA CDER Representative

Atlanta—The biosimilars market is a growing field of competition to branded therapeutic proteins and other biologic products. While it is recognized that these agents are playing an increasingly important role in the US pharmaceutical marketplace, confusion still exists regarding the pharmacologic properties of these agents in relation to their branded counterparts, and the regulatory guidelines regarding the approval and use of these agents.

During a Contemporary Issues session at the AMCP meeting titled Biosimilars: Considerations for Healthcare, Gilbert J. Burckart, PharmD, an associate director in the Office of Clinical Pharmacology at the US Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER), provided an overview of the pharmacology of biosimilars and the current regulatory process governing these products. Almost 75% of small-molecule prescriptions dispensed in 2009 were for generics, and the approval of a generic drug resulted in an average savings of 77% of the product’s cost within 1 year, Dr. Burckart noted. While similar cost reductions will probably not be possible with biosimilars, the Federal Trade Commission predicts that their availability could significantly reduce costs and increase accessibility, he added. As part of the Patient Protection and Affordable Care Act signed into law in 2010, the Biological Price Competition and Innovation (BPCI) Act was introduced and created an abbreviated biosimilar approval.

The current definition of a biologic product in the BPCI Act revises the former definition found in the Public Health Service (PHS) Act to specifically include protein products. Dr. Burckart noted that historically some proteins have been licensed as drugs under the Food, Drug, and Cosmetic Act, while others have been licensed under the PHS Act as biologics. He emphasized that under the most recent BPCI Act, any protein, except chemically synthesized polypeptide, will be regulated as a biologic product. Biologic products, including biosimilars, cannot be regulated like other drugs because they typically have a more complex structure, are made by living organisms, and require more complex methods for analysis, Dr. Burckart said. He elaborated by explaining some specific biochemical processes that result in protein heterogeneity and differences between branded biologic products and their biosimilar counterparts.

These differences can be difficult to determine in typical analyses, Dr. Burckart noted. He clarified the current general requirements for a biosimilar product. For instance, biosimilar products are required to use the same mechanism of action as the reference product, as well as the same route of administration, dosage form, and strength. Its production also needs to meet standards ensuring safety, purity, and potency. At least 1 clinical study, including the assessment of immunogenicity and pharmacokinetics (PK) or pharmacodynamics (PD), is sufficient to demonstrate these properties in ≥1 conditions for use for which the reference product is licensed. Dr. Burckart emphasized that highly similar comparative analytic and PK/PD data are associated with a lower risk of clinical differences.

From the perspective of drug coverage and reimbursement, Dr. Burckart explained that for a biosimilar product to be considered interchangeable, it must produce the same clinical result as the reference product in any given patient. In addition, for products administered more than once, the safety and reduced efficacy risks of alternating or switching between the reference and biosimilar product are not greater than the repeated use of the reference product. Biosimilars considered to be interchangeable may be substituted for the reference product without authorization from a healthcare provider. Dr. Burckart reviewed the exclusivity period that the FDA provides to licensed products. Specifically, applications for biosimilar products cannot be submitted until 4 years after the date of first licensure of the reference product. In addition, the application may not be approved until 12 years after the date of first licensure. This date does not include biologic license application supplements.

Dr. Burckart added that for pediatric approvals, exclusivity provisions for biologic products under the PHS Act do not attach to patents and can only attach to the 12-year exclusivity period, the 4-year filing period, or a 7-year orphan exclusivity period. To highlight the FDA’s commitment to biosimilar development, Dr. Burckart described 3 CDER committees convened to ensure that the FDA consistently regulates biosimilars. He added that the FDA is planning to issue draft guidance on biosimilars later this year.