In part 1, I described the state of play with regard to biologics after the FDA’s approval of its second biosimilar product Inflectra (infliximab). Now we turn to the regulatory process for such approval.

Before approving a biosimilar, the FDA requires the following:

  • Information demonstrating that the biological product is biosimilar to a reference product based upon data derived from:
    • analytical studies demonstrating that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components;
    • animal studies (including the assessment of toxicity); and
    • a clinical study or studies (including the assessment of immunogenicity and pharmacokinetics or pharmacodynamics) that are sufficient to demonstrate safety, purity, and potency in one or more appropriate conditions of use for which the reference product is licensed and intended to be used and for which licensure is sought for the biological product.  The design of these studies will differ depending on the type of biologic being studied.  The dose and route of administration should be the same as for the reference product.
  • Phase 3 clinical equivalency trials demonstrating that the proposed biosmilar has neither decreased nor increased activity relative to the reference product. That is, the goal is to demonstrate that any difference in efficacy or safety between the biosimilar and reference product is less than a prespecified margin of “clinical equivalence.”
  • Quality documents providing information on:
    • extensive characterization studies of both the active substance and the finished product; and
    • the development, manufacturing process, and quality control of both the active substance and the finished product. There should be a comparability exercise between the biosimilar and reference products on both the active substance and the finished products and the applicant should provide justification for any observed difference with regard to their potential impact on safety and efficacy. These differences can determine the amount of clinical data required for the biosimilar.
  • Pharmacovigilance Requirements
    • A report of local suspected serious or unexpected adverse drug reactions and periodic safety update reports.
    • Periodic Safety Update Reports on the biosimilar product every 6 months for the first 2 years, and then annually for the following 3 years after the registration is approved.

Information on the Risk Management Plan and/or Risk Evaluation and Mitigation Strategy for the biosimilar product as required by the reference agency if applicable, and any proposed local risk management plan activities and risk mitigation strategies, including a statement how these issues will be addressed in the post-marketing follow-up.  Finally, the proposed labelling for the healthcare professional and the patient must be provided.

As with generic drugs, increased availability of approved biosimilars will markedly decrease medical costs for patients, something which we all can get behind.