The study highlights that recent efforts to lower evidence standards for biosimilar approval, especially for interchangeability, have raised concerns. For example, a recent FDA meta-analysis pooled limited data from 44 studies across 21 biosimilars, concluding no significant safety differences between switched and non-switched patients. However, it is noted that the study's methodology, relying on single- and multi-switch studies without considering efficacy or individual patient variability, limits its validity. The authors also note that, broad conclusions risk undermining established safeguards, particularly for vulnerable populations.

In addition, proposals such as the 'Biosimilar Red Tape Elimination Act' [2] and President Biden's FY 2025 budget seek to eliminate the distinction between biosimilars and interchangeable biosimilars, bypassing switching studies and enabling unrestricted pharmacy-level substitution. Proponents argue this will boost biosimilar uptake, but US biosimilar adoption rates are already comparable to Europe, bolstered by the interchangeability standard.

The authors also note that cost-cutting policies risk patient safety and confidence in biosimilars, as automatic substitution may not address patient-specific factors or long-term effects. Legislative changes at federal and state levels, such as Oregon’s proposal to allow substitution of non-interchangeable biosimilars, threaten carefully crafted policies supported by medical and patient advocacy groups. They stress that maintaining rigorous standards for interchangeability is crucial to preserving patient trust, safety, and personalized care in biosimilar substitution practices. 

The US Food and Drug Administration (FDA) currently has discretion in determining the data required to grant an interchangeable designation, which may include switching studies. However, reducing evidence requirements for biosimilar interchangeability could undermine confidence in these complex drugs, as they differ from chemical medicines due to their variability and associated immune response risks.

Current reliance on analytical data over clinical studies leaves gaps in understanding the effects of switching, especially on efficacy. Eliminating the interchangeability standards risks patient safety, particularly for vulnerable populations, and disregards concerns about treatment disruptions caused by third-party substitutions.

Contrary to claims of alignment with Europe, where physician-led substitution is the norm, automatic pharmacy substitution of non-interchangeable biosimilars would diverge from European practices. Non-medical switching can lead to increased healthcare costs, adverse events, and patient stress, while undermining the patient-physician relationship. Physicians oppose payer-driven substitutions that force them to take responsibility for decisions beyond their control.

The authors emphasize that efforts to boost biosimilar adoption should focus on reforming pharmacy benefit manager (PBM) practices, which heavily influence market dynamics, rather than sacrificing rigorous standards that safeguard patient care and therapeutic stability.

The authors conclude that eliminating the criteria for the interchangeable designation through either guidance or legislation could undermine physicians' confidence in interchangeable biosimilars. Additionally, policies that declare all biosimilars interchangeable—thus substitutable at the pharmacy level—would break the assurances made to physicians and patients that only biosimilars with additional safety and efficacy data would be substituted without physician approval.

Related articles
Regulatory evolution and impact of simplified requirements for interchangeable biosimilars in the US

FDA proposal to remove biosimilar interchangeability status in FY25

FDA Guidance on Promotional Labelling and Advertising for Biologicals, Biosimilars and Interchangeables

References
1. Reilly MS, McKibbin RD. Misinformation about interchangeable biosimilars undermines US health policy, physician confidence, and patient health. Generics and Biosimilars Initiative Journal (GaBI Journal). 2024;13(2):55-60. doi:10.5639/gabij.2024.1302.009
2. GaBI Online - Generics and Biosimilars Initiative. ASBM/GaBI 2024 webinar on BIOSIMILAR RED TAPE ELIMINATION ACT (S2305) [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2025 Jan 21]. Available from: www.gabionline.net/conferences/asbm-gabi-2024-webinar-on-biosimilar-red-tape-elimination-act-s2305

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