In June, the U.S. Food & Drug Administration (FDA) released an updated version of its draft guidance on demonstrating biosimilar interchangeability. The FDA is no longer recommending a repeated switch study to demonstrate interchangeability of biosimilars. Instead, it will accept an assessment of why the comparative analytical and clinical data in the application or supplement shows that the switching standard outlined in section 351(k)(4)(B) of the Public Health Service Act has been met. Applicants with a pending biologics license application (BLA) for a proposed biosimilar can submit an amendment with such an assessment for interchangeability review.
The guidance was first issued in 2019, and the FDA has said the updated version reflects the experience gained in the nearly 10 years since the first biosimilar was approved in the U.S., which has shown that biosimilars are typically safe and effective, even when switching between versions multiple times.
Alongside the draft guidance, FDA also published a blog post explaining biosimilars and interchangeable biosimilars. In the post, the agency said that by updating the guidance and possibly requiring fewer studies, it aims to create a framework that will allow interchangeable biosimilars to come to market faster while ensuring the same level of safety and effectiveness.
Impact on Rheumatology
Since the introduction of the first biosimilar, the discussion about their interchangeability has persisted. There are no data suggesting that switching to a biosimilar jeopardizes patient safety.
The requirement for switching studies for designation as an interchangeable biosimilar was intended to ensure that such switches can be done safely by examining any immunogenicity risks. As the FDA notes, switching between biosimilars has been found to generally be safe and effective, with no differences in efficacy, safety or immunogenicity. Requiring switching studies for biosimilar approval thus appears superfluous and may represent a barrier to patient access. Therefore, the ACR supports the removal of this requirement.
However, the ACR maintains that the key concern around switching biosimilars is the nocebo effect, which reinforces the need for physician involvement when switching. A recent report has shown that the proliferation of interchangeable status among biosimilars leads to more pharmacy-level substitutions, often occurring without timely notification of the prescribing provider and the patient.[1] Additionally, these switches are frequently the result of mandates from insurers or pharmacy benefit managers. They are often implemented for cost-related reasons, with minimal regard for the patient’s well-being. They also create a significantly high degree of administrative burden for the prescribing provider and logistical challenges for the patient, who may be required to procure a new co-pay card if the biosimilar manufacturer did not develop the reference product.
The ACR is fiercely dedicated to ensuring that guardrails remain in place for patient safety when switches occur. ACR/ARP members should email the ACR’s advocacy team at [email protected] with any questions and comments they may have. We will monitor the rule’s implementation and serve as an educational resource for members on its provisions and the impact they will have on rheumatology.
Read the ACR’s comments on this proposal to the FDA.
Reference
[1] Focus on interchangeable biosimilars. The American Pharmacists Association. 2024.
