Biosimilars: still safe, still effective, still not generics. Why is FDA suddenly pretending they are?
Published on 12 January 2026
Generics and Biosimilars Initiative Journal (GaBI Journal). 2026;15(1).
Abstract: |
Introduction
When US Health and Human Services (HHS) Secretary Robert F Kennedy Jr recently announced [1] a new US Food and Drug Administration (FDA) initiative to fast-track biosimilar approvals, he presented it as a long-overdue correction of a system rigged by industry and not based on science. In his telling, the pharmaceutical industry has exaggerated the complexity of biologic[al]s and then invented a fake distinction between biosimilars and interchangeable biosimilars to block competition and keep prices high.
At the same event, FDA Commissioner Marty Makary invited the public [2] to think of biosimilars as the generic version of the expensive biologicals, pledging to eliminate comparative clinical studies for most biosimilars and so-called bureaucratic switching studies for interchangeable products, cutting approval timelines cut in half and encouraging automatic pharmacy substitution.
These are not minor technical tweaks. Taken together, they amount to a deliberate genericization of biosimilars: collapsing the long-established scientific distinction between biologicals and small-molecule drugs and converting a carefully built biosimilar framework into a generic-style mass-substitution model.
Under Secretary Kennedy, FDA policy has been marked by abrupt shifts, highly public internal disagreements, and notable leadership turnover. Within this unsettled context, the genericization initiative is arguably the strangest departure: it explicitly discards core concepts that FDA, international regulators, and the scientific community have treated as foundational since the first biosimilar approvals. Current science/regulation is built on structured, stepwise demonstration of similarity using analytic, functional, and clinical evidence — acknowledging biological complexity — rather than assuming equivalence by simple comparison of active ingredients; genericization would discard that entire scaffold.
For those of us who have spent the past 15–20 years helping build global biosimilar policy—including through the GaBI Journal itself—this is not an evolution. It is a repudiation of the scientific foundation on which biosimilar regulation was built.
Global regulators agree: biosimilars are not generics
Every major medicine regulator in the world has confronted the question posed by HHS: are biosimilars simply generics by another name? All have answered, unequivocally, no—because biologicals cannot be fully characterized by chemistry alone, and small differences in structure, manufacturing, or use conditions may have clinically meaningful effects. Accordingly, these authorities have built distinct pathways, data requirements, nomenclature systems, and pharmacovigilance structures to reflect this reality.
A few examples illustrate the global consensus:
- Australia’s Therapeutic Goods Administration (TGA) affirms [5] that a biosimilar is not a generic biological medicine, and that principles relevant to generics cannot be simply extrapolated to biosimilars.
- The European Medicines Agency (EMA) states [3] that a biosimilar is not regarded as a generic of a biological medicine, and that more studies are required for regulatory approval of biosimilars than for generics.
- Health Canada notes [4] that, unlike generic drugs, biosimilars can never be identical to their reference biological drug, and requires comparative structural, functional, [pharmacokinetic/pharmacodynamic] and, where needed, clinical data.
The World Health Organization’s similar biotherapeutic products guideline likewise rejects [6] a simple generic approach for biologicals, as do Japan’s Pharmaceuticals and Device Agency (PMDA) [7], Brazil’s Health Regulatory Agency (ANVISA) [8] and those of other advanced regulators.
These policies were developed independently by regulators and scientific committees in recognition of a basic fact: biologicals cannot be fully characterized through chemistry alone, and small differences—whether in structure, formulation, device, or use conditions—can be clinically meaningful.
In this light, the new US rhetoric is remarkable. If the Administration now believes the distinction between biosimilars and generics is fake, it is not merely rejecting industry’s view. It is declaring that the historical position of FDA itself [9]—and that of EMA, WHO, Health Canada, TGA, PMDA, ANVISA and others—has been wrong for nearly two decades.
The ‘interchangeable’ standard is not ‘made up’
Secretary Kennedy went further, alleging that industry invented a distinction between biosimilars and interchangeable biosimilars simply to prevent pharmacists from substituting lower-cost products. That misstates the science, the policy history, and the law.
Under the Biologics Price Competition and Innovation Act of 2009 (BPCI Act) [10], biosimilarity asks whether a product is highly similar to the reference with no clinically meaningful differences at the population level. Interchangeability then adds a patient-level requirement: that the product can be expected to produce the same clinical result in any given patient, and, for products administered more than once, alternating or switching must not present greater risk in terms of safety or diminished efficacy.
This is not a semantic trick. It reflects real-world variables that lie outside the reach of analytics alone: device and delivery differences, human-factors considerations, comorbidities, concomitant medicines, prior treatment failures and individual immunogenicity risk. FDA has long acknowledged that such factors may warrant additional switching data for products that will be substituted by third parties.
Just as importantly, the US interchangeable designation is the legal key that unlocks generic-style automatic substitution under US state pharmacy laws. State legislatures, working closely with medical societies and patient groups over nearly a decade, unanimously agreed [11] that only biosimilars meeting this higher standard should be substituted at the pharmacy without prescriber involvement. Patients and clinicians were explicitly assured that third-party substitution would be supported by clinical data- beyond that merely required for approval, to ensure switching did not jeopardize treatment stability.
Dismissing the interchangeable designation as fake ignores both this scientific rationale and that legislative history—and calls into question commitments made to physicians and patients when states agreed to allow substitution at all.
From analytics-plus to analytics-only and all interchangeable
The new FDA policy, as described by HHS and FDA leadership and by outside analyses, rests on two pillars:
- Eliminating most comparative clinical efficacy studies for biosimilars, with approvals relying primarily on analytical assessments and limited pharmacokinetic/pharmacodynamic (PK/PD) data
- Removing the current data requirements for interchangeables so that, in Commissioner Makary’s words, every biosimilar should have the designation of interchangeable.
The Association for Accessible Medicines—a trade group representing more than 28 aligned [12]manufacturers and 11 associate organizations [13]—has called the interchangeability category ‘unnecessary and confusing’. It has urged FDA to treat any approved biosimilar as interchangeable. Coupled with these statements, the practical endpoint is clear: an analytics-only standard for approvals, followed by a de facto class-wide automatic substitution regime.
No serious stakeholder disputes that analytical tools have improved dramatically or that some comparative clinical trials add limited marginal value. Thoughtful streamlining is both possible and desirable. But abandoning clinical confirmation at scale and erasing the legal and scientific distinction that underpins safe third-party switching is something very different—and far riskier.
Physicians and patients do not want genericization
The available data show that physician do not support treating all biosimilars as generics. A 2024 national survey [14] of 270 US biologicals prescribers found that:
- Only 11% favour treating all biosimilars as interchangeable by default
- 88% support FDA’s current case-by-case evaluation standard for interchangeables
- The same proportion—88%—say switching studies (which FDA has required in some but not all cases) increase their confidence in interchangeables.
Earlier surveys reported [15] in GaBI Journal similarly show that the nearly all US prescribers (89%) are highly confident in and comfortable using biosimilars, but a strong majority (69%) are wary of non-medical switching by third parties [16, 17] especially when it may destabilize well-controlled patients. A 2019 survey of U.S. gastroenterologists, dermatologists, and rheumatologists found that 84% of these specialists did not want stable patients to undergo non-medical switching to a biosimilar. Consistent with this, a 2020 analysis of 23 studies of US and European physician attitudes revealed 64%–95% had negative perceptions of pharmacist-led substitution of biological medicines [18]. A 2021 Belgian survey found a majority of physicians opposed automatic substitution [17].
European experience is often invoked to justify generic-style substitution in the US, yet the European data [19]tell a similar story. Like their US counterparts, EU prescribers are highly confident in biosimilar quality and often willing to start new patients on them, yet 76% oppose pharmacy-level substitution without the involvement of the prescribing doctor. This generic-style automatic substitution remains rare among European countries [20] and often expressly prohibited [21] in many Western European countries.
Across jurisdictions, clinicians draw a sharp line between prescriber-led switches based on clinical judgement and automatic switches by insurers or pharmacies driven by their financial benefit to intermediaries (as opposed to patients) [21-24]. As recently as 2024, health-policy literature has reaffirmed this distinction, defining switching as a prescriber-led clinical decision and automatic substitution as a third-party action without prescriber involvement, and underscoring why clinicians have sought to preserve this boundary [20]. FDA’s new policy blurs that line in precisely the way physicians have asked regulators to avoid.
The real access barrier: PBM and payer incentives
The rationale offered by HHS is that traditional biosimilar development is too slow and expensive, leaving the US behind Europe in approvals and uptake. When considering these claims, is important to note that Europe created its approval pathway ten years earlier than the US, and that the US is catching up- with an approval rate three times faster [22]. Nevertheless, it is undeniable comparative clinical studies do add time and cost to approvals.
Still, this diagnosis is, at best, incomplete.
As many independent analyses have repeatedly documented [25-27], the primary constraints on biosimilar use in the US are formulary design and rebate-driven contracting by insurers and pharmacy benefit managers (PBMs), not FDA’s evidence-based approval standards.
When a large PBM opts to prefer its own co-branded biosimilar or a particular contracting partner, market share can swing from single digits to a third of the market in a week [28]—without any change in FDA policy. In his announcement, Sec. Kennedy cited the example of the popular biological Humira (adalimumab) for which there are 10 FDA-approved biosimilars, 8 of which are designated interchangeable, selling [29] at 22 different price points and offering up to 92% discount [30] over the originator product. Nevertheless, the original product maintains [31] roughly 80% market share. Formulary placement and exclusions—which are driven by profitability [29, 32] and often favour PBM-owned products [33-35]—have largely determined which products patients actually receive.
Market competition between the many Humira biosimilars under FDA standards has effectively lowered the price- and done so without sacrificing safety or treatment stability. Yet patient access is constrained not by FDA scientific standards- but by opaque financial incentives in the PBM formulary design and rebating system. Lowering approval standards and declaring all biosimilars interchangeable will not reform rebate games or ensure that savings reach patients instead of the insurance company or PBM shareholder; it will merely expand the ability of these intermediaries to force switches to the products that are most profitable to them.
First respect the science, then debate the policy
The Generics and Biosimilars Initiative and the GaBI Journal were founded on a simple but profound insight: biosimilars require tailored policies precisely because they are not generics. For more than a decade, this journal has hosted rigorous debates over naming, traceability, non-medical switching, substitution rules, and data requirements- many authored by regulators and leading clinicians.
Those debates have been spirited, and reasonable people disagree about the optimal design of tenders, how much clinical data is truly necessary in specific classes, what nomenclature approach best suits the unique pharmacovigilance needs of biosimilars, and yes- if and under what conditions may biosimilars be substituted by at the pharmacy level. But until now, these arguments have taken place within a shared frame: that complex biologicals demand a distinct, science-driven regulatory architecture.
The HHS ‘genericization’ initiative steps outside that frame. By declaring the foundational distinction ‘fake’,equating biosimilars with generics, and pushing toward analytics-only approvals with class-wide interchangeability (in the US sense of the term, i.e. meaning automatic pharmacy substitution), it discards the premise that has made global biosimilar regulation possible. It also runs counter to previous analyses by regulators [36] and in GaBI Journal [37] warning that misinformation about interchangeable biosimilars can undermine health policy, physician confidence, and patient health.
We can and should continue to refine biosimilar development requirements as analytics evolve. We can debate how often, and in which settings, switching studies add value. But we should not pretend that eliminating clinical confirmation altogether and enabling mass third-party automatic substitution is simply modernizing the science. It is rejecting inconvenient but long-established science in support of a political goal.
Data-driven confidence, not data-free substitution
Biosimilars have already delivered substantial savings—more than $54 billion dollars in the US alone—with potential for much more. That promise will only be fully realized if physicians and patients continue to trust both the products and the system that approves and oversees them.
A more sustainable path is available. The Alliance for Safe Biologic Medicines and others have urged FDA to maintain rather than weaken approval standards while Congress continues to address PBM rebate and formulary practices which act as barriers to biosimilar access.
- Maintain a totality-of-evidence paradigm in which robust analytics are complemented, where appropriate, by targeted clinical and switching data
- Preserve FDA’s flexible, case-by-case authority to request additional data when human-factors, device, or patient-specific variables warrant it
- Uphold the interchangeability framework as the gatekeeper for third-party automatic substitution, rather than declaring all biosimilars interchangeable by fiat
This approach aligns with the views of most US and European prescribers, respects the scientific consensus among regulators worldwide, and preserves the delicate balance between encouraging competition and protecting patient safety.
We welcome the Administration’s stated desire to expand access to biological therapies and reduce costs for patients. We agree that biosimilar development should be as efficient as science allows, and that the US should learn from Europe’s successes in fostering competition.
But denying the scientific distinctiveness of biologicals, discarding clinical confirmation wholesale, and collapsing biosimilars into a generic-style automatic substitution model is not the way to get there. It risks destabilizing treatment for millions of patients, eroding hard-won physician confidence, and undermining public trust in FDA’s drug-approval standards.
For more than two decades, regulators, clinicians, patients, and journals like GaBI have worked to build a global biosimilar ecosystem that is both competitive and safe. The HHS genericization policy turns its back on that shared work. We urge FDA and HHS to reconsider, to re-engage with the international scientific and clinical community, and to restore a biosimilar pathway grounded in biology, clinical reality, and global regulatory science.
Funding sources
The article was funded by the Alliance for Safe Biologic Medicines (ASBM).
ASBM is a coalition of patient advocacy organizations, physicians, pharmacists, biopharmaceutical manufacturers, and others working to advance patient-centred health policy at the state, federal, and international level. Visit www.SafeBiologics.org to learn more.
Competing interests: Mr Michael S Reilly, Esq is the Executive Director and employed by Alliance for Safe Biologic Medicines. Mr Reilly served in the US Department of Health and Human Services from 2002 to 2008.
Provenance and peer review: Not commissioned; externally peer reviewed.
Authors
Michael S Reilly, Esq
Professor Philip J Schneider, MS, FASHP, FASPEN, FFIP
Andrew Spiegel, Esq
References
1. Kennedy RF Jr. Remarks announcing proposed FDA drug approval changes. Video recording. YouTube. Available from: https://youtu.be/UaphBlIIm-8
2. Rev. Transcript: RFK Jr. announces FDA drug approval changes. Available from: https://www.rev.com/transcripts/rfk-jr-announces-fda-drug-approval-changes
3. European Medicines Agency. Biosimilars in the EU: information guide for healthcare professionals [homepage on the Internet]. [cited 2026 Jan 5]. Available from: https://www.ema.europa.eu/en/documents/leaflet/biosimilars-eu-information-guide-healthcare-professionals_en.pdf
4. Health Canada. Handbook for health care professionals on biosimilar biologic drugs: Overview [homepage on the Internet]. [cited 2026 Jan 5]. Available from: https://www.canada.ca/en/health-canada/services/drugs-health-products/biologics-radiopharmaceuticals-genetic-therapies/biosimilar-biologic-drugs/handbook-healthcare-professionals.html
5. Australian Government. Therapeutic Goods Administration. Evaluation of biosimilars [homepage on the Internet]. [cited 2026 Jan 5]. Available from: https://www.tga.gov.au/sites/default/files/pm-argpm-biosimilars-150420_1.pdf
6. World Health Organization. Guidelines on evaluation of biosimilars [homepage on the Internet]. [cited 2026 Jan 5]. Available from: https://cdn.who.int/media/docs/default-source/biologicals/annex-3—who-guidelines-on-evaluation-of-biosimilars—sj-ik-5-may-2022.pdf
7. Pharmaceuticals and Medical Devices Agency. Guidelines for biosimilars [homepage on the Internet]. [cited 2026 Jan 5]. Available from: https://www.pmda.go.jp/files/000153851.pdf
8. Instituto Dannemann Siemsen. ANVISA’s Formal Statement No. 003/2017 on interchangeability of biological drugs (biosimilars) [homepage on the Internet]. [cited 2026 Jan 5]. Available from: https://ids.org.br/en/anvisas-formal-statement-no-003-2017-gpbio-ggmed-on-interchangeability-of-biological-drugs-biosimilar/
9. U.S. Food and Drug Administration. Biosimilars info sheet [homepage on the Internet]. [cited 2026 Jan 5]. Available from: https://www.fda.gov/media/154912/download
10. U.S. Food and Drug Administration. Biological product innovation and competition [homepage on the Internet]. [cited 2026 Jan 5]. Available from: https://www.fda.gov/drugs/biosimilars/biological-product-innovation-and-competition
11. National Association of Chain Drug Stores. State substitution practices for biological drugs [homepage on the Internet]. [cited 2026 Jan 5]. Available from: https://www.nacds.org/pdfs/government/2021/State-Substitution-Practices-for-Biological-Drugs-chart-July-2021.pdf
12. Association for Accessible Medicines. FDA biosimilars and clinical interchangeability [homepage on the Internet]. [cited 2026 Jan 5]. Available from: https://accessiblemeds.org/resources/press-releases/fda-biosimilars-clinical-interchangeability/
13. Association for Accessible Medicines. Member organizations (2025) [homepage on the Internet]. [cited 2026 Jan 5]. Available from: https://accessiblemeds.org/about/our-members
14. Alliance for Safe Biologic Medicines. ASBM physician survey on interchangeable biosimilars finds support for maintaining current standards [homepage on the Internet]. [cited 2026 Jan 5]. Available from: https://safebiologics.org/asbm-physician-survey-on-interchangeable-biosimilars-finds-support-for-maintaining-current-standards/
15. Reilly MS, McKibbin RD. U.S. prescribers’ attitudes and perceptions about biosimilars. Generics and Biosimilars Initiative Journal (GaBI Journal). 2022;11(3):96-103. doi:10.5639/gabij.2022.1103.016
16. Teeple, A, Ellis, LA, Huff, L, Reynolds, C, Ginsburg, S, Howard, L, Walls, D, Curtis, JR. Physician attitudes about non-medical switching to biosimilars: Results from an online physician survey in the United States. Curr Med Res Opin. 2019 Apr;35(4), 611–7. doi.org/10.1080/03007995.2019.1571296
17. Barbier, L, Vandenplas, Y, Simoens, S, Declerck, P, Vulto, AG, Huys I. Knowledge and perception of biosimilars in ambulatory care: A survey among Belgian community pharmacists and physicians. J Pharm Policy Pract. 2021 Jun 22;14:53. doi:10.1186/s40545-021-00330-x
18. Sarnola, K, Merikoski, M, Jyrkkä, J, & Hämeen-Anttila, K. Physicians’ perceptions of the uptake of biosimilars: A systematic review. BMJ Open. 2020 May 5;10(5): e034183. doi:10.1136/bmjopen-2019-034183
19. Feldman ME, Reilly MS. European prescribers’ attitudes and beliefs on biologicals prescribing and automatic substitution. Generics and Biosimilars Initiative Journal (GaBI Journal). 2020;9(3):116-24. doi:10.5639/gabij.2020.0903.020
20. Machado S, Cruz Agostinho, Ferreira PL, Morais C, Pimenta RE. Policy measures and instruments used in European countries to increase biosimilar uptake: a systematic review Front. Public Health. 28 Feb 2024. Sec. Public Health Policy
21. Reilly MS, Schneider PJ. Key factors for successful uptake of biosimilars in Europe and the U.S. Generics and Biosimilars Initiative Journal (GaBI Journal). 2022;11(3):112-24. doi:10.5639/gabij.2022.1103.018
22. American College of Physicians. Statement of the American College of Physicians to the U.S. Energy and Commerce Health Subcommittee Hearing on an examination of how reining in PBM’s will drive competition and lower costs for patients. February 26,2025. Available from: https://www.acponline.org/sites/default/files/acp-policy-library/testimony/acp_statement_to_the_house_energy_and_commerce_health_subcommittee_on_pharmacy_benefit_managers_pbms_hearing_2025.pdf
23. Community Oncology Alliance position statement on biosimilars. Available from: https://assets.mycoa.io/1762552841992_COA-PositionStatement-Biosimilars-v7-Clean.pdf
24. American Medical Association. The impact of pharmacy benefit managers on patients and physicians. Available from: https://www.ama-assn.org/system/files/2019-07/a19-cms-report-5.pdf
25. Yeung K, Dusetzina SB, Basu A. Association of Branded Prescription Drug Rebate Size and Patient Out-of-Pocket Costs in a Nationally Representative Sample, 2007-2018. JAMA Network Open. 2021;4;(6):e2113393. doi:10.1001/jamanetworkopen.2021.13393
26. Mattingly II J, Hyman DA. Pharmacy benefit managers: history, business practices, and policy. JAMA Health Forum. 2023;4;(11):e233804.
27. Federal Trade Commission. Pharmacy benefit managers: the powerful middlemen inflating drug costs and squeezing main street pharmacies. [homepage on the Internet]. [cited 2026 Jan 5]. Available from: https://www.ftc.gov/system/files/ftc_gov/pdf/pharmacy-benefit-managers-staff-report.pdf
28. Thanks to CVS, a biosimilar version of AbbVie’s Humira is grabbing huge market share. STAT News.Available from: https://www.statnews.com/pharmalot/2024/04/15/cvs-abbvie-humira-biosimilar-medicines-biologic-arthritis/
29. The big three PBMs’ 2025 formulary exclusions: Humira, Stelara, Private Labels, and the shaky future for pharmacy biosimilars. Drug Channels Institute. Available from: https://www.drugchannels.net/2025/01/the-big-three-pbms-2025-formulary.html
30. GoodRx. Adalimumab-adbm. Available from: https://www.goodrx.com/adalimumab-adbm
31. AbbVie’s Humira continues to lose market share as biosimilars gain ground. BioSpace. Available from: https://www.biospace.com/business/abbvies-humira-continues-to-lose-market-share-as-biosimilars-gain-ground-report
32. U.S. House Committee on Oversight and Accountability. The role of pharmacy benefit managers in prescription drug markets [homepage on the Internet]. [cited 2026 Jan 5]. Available from: https://oversight.house.gov/wp-content/uploads/2024/07/PBM-Report-FINAL-with-Redactions.pdf
33. How PBMs are reshaping biosimilar market access. MMIT Network. 31 July 2025.
34. PBMs’ private-label biosimilar strategies and market impact. BioxEconomy. 2 September 2025.
35. Big 3 PBM formularies favor private-label biosimilars. Becker’s Hospital Review.
36. U.S. Food and Drug Administration. FDA and FTC announce new efforts to further deter anti-competitive business practices, support competitive market for biological products to help Americans [homepage on the Internet]. [cited 2026 Jan 5]. Available from: https://www.fda.gov/news-events/press-announcements/fda-and-ftc-announce-new-efforts-further-deter-anti-competitive-business-practices-support
37. Reilly MS, McKibbin RD. Misinformation about interchangeable biosimilars undermines U.S. 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
Author for correspondence: Michael S Reilly, Esq, Executive Director, Alliance for Safe Biologic Medicines, PO Box 3691, Arlington, VA 22203, USA |
Disclosure of Conflict of Interest Statement is available upon request.
Copyright © 2026 Pro Pharma Communications International
Permission granted to reproduce for personal and non-commercial use only. All other reproduction, copy or reprinting of all or part of any ‘Content’ found on this website is strictly prohibited without the prior consent of the publisher. Contact the publisher to obtain permission before redistributing.
