This article examines the evolving regulatory landscape for simplified requirements for interchangeable biosimilars in the US. It explores recent US Food and Drug Administration (FDA) approvals, the role of switching studies, and updated labelling guidance, highlighting key changes and their implications for biosimilar development and use.
In June 2024, FDA issued draft guidance proposing the removal of the requirement for repeated switching studies to demonstrate biosimilar interchangeability [1]. This marks a significant shift in the regulatory landscape for biosimilars.
Overview of switching studies in FDA's biosimilar approvals
At the end of June 2024, FDA had approved 56 biosimilars, 13 of which were designated as interchangeable [2]. Of these, nine were approved without the need for clinical switching studies.
- Switching studies were conducted for two adalimumab biosimilars and one insulin-glargine biosimilar.
- One insulin-glargine biosimilar and two ranibizumab biosimilars were approved without switching studies.
- A ustekinumab biosimilar was approved without clinical switching data, as the applicant provided sufficient evidence that the risk of alternating or switching between the biosimilar and originator Stelara was no greater than using Stelara alone.
- Six additional biosimilars have since been approved as interchangeable, also without clinical switch data.
FDA will now consider comparative analytical and clinical data as meeting the requirements of Section 351(k)(4)(B) of the Public Health Service Act for interchangeability. Applicants with pending Biologics License Applications (BLA) for biosimilars may submit amendments to include interchangeability assessments.
Updated guidance on labelling for biosimilars
In addition to revising the requirements for switching studies, FDA has also updated its guidance on labelling for interchangeable biosimilars.
In September 2023, FDA proposed changes to the labelling requirements in its draft guidance titled, Labeling for Biosimilar and Interchangeable Biosimilar Products: Guidance for Industry [3]. These updates, once finalized, will replace the 2018 FDA guidance and sections from the 2020 draft guidance, Biosimilarity and Interchangeability: Additional Draft Q&As on Biosimilar Development and the BPCI Act.
Key changes in the 2023 biosimilar labelling guidance:
- Removal of the interchangeability statement
- Clarification on product identification when the reference product label refers to a non-US-approved biological
- Revised paediatric use statements
- Inclusion of relevant immunogenicity data from the reference product
The new draft guidance also recommends that labels for both biosimilars and interchangeable biosimilars include a ‘biosimilarity statement’, such as PRODUCT X (monoclonal-xxxx) is biosimilar to INNOVATOR (monoclonal-yyyy). FDA believes it is unnecessary to include an interchangeability statement, as it is not essential for informing healthcare professionals about the safe and effective use of the product.
Despite these regulatory evolutions, the Alliance for Safe Biologic Medicines argues that the change in interchangeable biosimilars requirements ‘would result in widespread generic-style automatic substitution at the pharmacy level … Physician confidence in biosimilars remains high, and the interchangeable standard has effectively built trust. Additionally, biosimilar uptake is influenced by formulary design, not interchangeability. Targeting pharmacy benefit managers practices could better support biosimilar adoption’ [4].
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References
1. GaBI Online - Generics and Biosimilars Initiative. FDA interchangeable biosimilars guidance update on revised approach to switching studies [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2024 Sep 18]. Available from: www.gabionline.net/guidelines/fda-interchangeable-biosimilars-guidance-update-on-revised-approach-to-switching-studies
2. GaBI Online - Generics and Biosimilars Initiative. Biosimilars approved in the US [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2024 Sep 18]. Available from: www.gabionline.net/biosimilars/general/biosimilars-approved-in-the-us
3. GaBI Online - Generics and Biosimilars Initiative. FDA issues draft guidance on biosimilars and interchangeable biosimilars labelling [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2024 Sep 18]. Available from: www.gabionline.net/guidelines/fda-issues-draft-guidance-on-biosimilars-and-interchangeable-biosimilars-labelling
4. Reilly MS. Preserve the US interchangeable standard that has helped drive physician and patient confidence in biosimilars. Generics and Biosimilars Initiative Journal (GaBI Journal). 2024;13(1):34-6. doi:10.5639/gabij.2024.1301.006
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