Biosimilars Handbook

What Does the Law Say?

To regulate this emerging field of science, the United States Congress established a new framework for scientists and manufacturers seeking approval to make new biosimilar therapies available to patients. As part of the landmark Patient Protection and Affordable Care Act (ACA) of 2010, the Biologics Price Competition and Innovation Act (BPCIA) lays out requirements for the approval of biosimilars and interchangeable biologic products and assigned FDA the task of designing the detailed approval pathway for these medicines.

The BPCIA requires that a biosimilar must demonstrate no clinically meaningful difference from its reference biologic in terms of safety and quality metrics like purity and potency. This means patients and health care professionals can rely upon the fact that a biosimilar medicine or interchangeable biologic will treat the same disease as safely and effectively as the original brand product. It is important to understand that the interchangeability designation does not represent a “higher” standard than for a biosimilar product, but rather adds the requirement for additional scientific data related to multiple switches between products. Per the law, a biosimilar must meet safety, efficacy and quality requirements and can be used for all approved indications of the reference product. (see Appendix for the full text of the law).

Public Health Service Act—Section 351(k)(2)(A)(i) —

  • The biological product is similar to the reference product based upon data derived from:
    • (aa) analytical studies (bb) animal studies
    • (cc) a clinical study or studies (including the assessment of immunogenicity and pharmacokinetics or pharmacodynamics);
  • The biological product and reference product utilize the same mechanism or mechanisms of action;
  • The condition or conditions of use prescribed, recommended, or suggested in the labeling have been previously approved for the reference product;
  • The route of administration, the dosage form, and strength are the same;
  • The facility where the biological product is produced meets standards to ensure that the biosimilar is safe, pure, and potent.

The BPCIA further provides that for a medicine to be an interchangeable biologic product, it must be expected to produce the same clinical result in any given patient as the brand biologic. In addition, where a product is administered more than once, it must be shown that alternating between the interchangeable biologic and the original or “reference product” counterpart does not raise concerns. This designation means that an interchangeable biologic product is just that, interchangeable: it may be substituted for an original product without the intervention of the health care provider that prescribed the original product. Section 351(k)(4) of the Public Health Service Act specifies criteria for determining whether a biosimilar is interchangeable with the reference product:

  • “(4) Safety Standards for Determining Interchangeability. —Upon review of an application submitted under this subsection or any supplement to such application, the Secretary shall determine the biological product to be interchangeable with the reference product if the Secretary determines that the information submitted in the application (or supplement to such application) is sufficient to show that—
  • the biological product—
    • is biosimilar to the reference product; and
    • can be expected to produce the same clinical result as the reference product in any given patient; and
    • for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product is not greater than the risk of using the reference product without such alternation or switch.”