What does the designation of interchangeability for biosimilars in the US mean?

Biosimilars/Research | Posted 02/09/2022 post-comment0 Post your comment

Biologicals have significantly improved patients’ quality of life, yet, access to these critical medicines are constrained due to cost and this is being exacerbated by the misperceptions around biosimilars. In particular, imprecise terminology has been applied to biosimilars, leading to the implication that biologicals designated as interchangeable by the US Food and Drug Administration (FDA) are better biosimilars. The US is the only jurisdiction in the world with this additional designation from the regulator as an option for biosimilar sponsors to consider [1].

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In their recently published article on interchangeability, Samsung Bioepis discusses the meaning of the FDA’s designation of interchangeability for a biosimilar in the US and show what this designation means in legal and clinical terms [2]. The authors highlight the need for further education by FDA and identify which stakeholders likely need that education the most.

Interchangeability is not a higher quality standard. An interchangeable biosimilar is a biosimilar upon which additional studies may have been conducted on the exact same product. Since no modification is made to the biosimilar product itself in order to achieve an interchangeability designation, and indeed none would be allowed from a regulatory standpoint, biosimilars in the US are never not interchangeable, they are just not yet designated as interchangeable by FDA. As such, there is a close parallel to Europe, where the regulations are silent on interchangeability as a regulatory matter [3]. In fact, in the European Union (EU), decisions on the interchangeability or substitution of biosimilars and originator biologicals are not made by the European Medicines Agency (EMA), but at the national level. Biosimilars developed in line with EU requirements are considered by EMA to be therapeutic alternatives to their reference biologicals [4].

Fundamentally, the interchangeability designation is not about prescribing, but is a legal distinction that enables pharmacists (subject to state law) to substitute a biosimilar in lieu of its reference product without prior approval from the prescriber. The outcomes for the patient will be the same whether the switch is made by the physician or pharmacist as a clinical matter, but the authorities are quite distinct as a legal matter and defined in the law that created the options for biosimilars in the US – the Biologics Price Competition and Innovation Act of 2009 (BPCI Act) [5]. As a clinical matter, all biosimilars are interchangeable in that they can be exchanged for the reference product that is expected to have the same clinical effect. Physicians can use any medicine on or off label as appropriate to the patient and have routinely switched products, even closely related ones, as a means to optimize care. As such, physicians can prescribe biosimilars just like any other medicines for any purpose.

While physicians might perceive the need for an interchangeability designation for additional assurance to assist in their own decisions to switch patients to biosimilars, this is due to the misperception of what it actually means to be designated as interchangeable in the US. In order to facilitate biosimilar uptake and increased patient access, FDA needs to rectify the misperception around biosimilars, including that ‘interchangeable biosimilar’ denotes a higher standard of biosimilar, by educating the stakeholders involved, especially the physicians. Physicians, pharmacists and their patients should have as much confidence as they historically have had with the originator product in switching the care for any given patient between any biosimilar to the same reference, and with that same reference itself.

Conflict of interest
The authors of the research paper [2] reported conflict of interest, including being an employee of Samsung Bioepis. For full details of the authors’ conflict of interest, see the research paper [2].

Abstracted by Joseph P Park, Samsung Bioepis, Yeonsugu, Incheon, Republic of Korea.

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1. GaBI Online - Generics and Biosimilars Initiative. Interchangeability of biosimilars in the US [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2022 Sep 2]. Available from: www.gabionline.net/reports/Interchangeability-of-biosimilars-in-the-US
2. Park JP, Jung B, Park HK, et al. Interchangeability for biologics is a legal distinction in the usa, not a clinical one. BioDrugs. 2022;36(4):431-6.
3. Kurki P, van Aerts L, Wolff-Holz E, et al. Interchangeability of biosimilars: a European perspective. BioDrugs. 2017;31(2):83-91.
4. GaBI Online - Generics and Biosimilars Initiative. Biosimilar substitution in Europe [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2022 Sep 2]. Available from: www.gabionline.net/reports/Biosimilar-substitution-in-Europe
5. GaBI Online - Generics and Biosimilars Initiative. Biosimilarity and interchangeability under the BPCI Act [www.gabionline.net]. Mol, Belgium: Pro Pharma Communications International; [cited 2022 Sep 2]. Available from: www.gabionline.net/biosimilars/research/Biosimilarity-and-interchangeability-under-the-BPCI-Act

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