Biosimilars: Still Safe, Still Effective, Still Not Generics. Why is the FDA Suddenly Pretending They Are?
Published on 2025/12/04
Abstract: |
Introduction
At the same event, FDA Commissioner Marty Makary invited the public to “think of biosimilars as the generic version of the expensive biologics,” pledging to eliminate comparative clinical studies for most biosimilars and so-called “bureaucratic switching studies” for interchangeable products, cutting approval timelines 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 biologics 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.
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 medicines regulator in the world has confronted the question posed by HHS: are biosimilars simply generics by another name? All have answered, unequivocally, no—and have built distinct pathways, data requirements, nomenclature systems, and pharmacovigilance structures accordingly.
A few examples illustrate the global consensus:
- The European Medicines Agency (EMA) states 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 that, “unlike generic drugs, biosimilars can never be identical to their reference biologic drug,” and requires comparative structural, functional, PK/PD and, where needed, clinical data.
- Australia’s TGA affirms that “a biosimilar is not a generic biological medicine,” and that principles relevant to generics “cannot be simply extrapolated” to biosimilars.
The World Health Organization’s similar biotherapeutic products guideline likewise rejects a simple generic approach for biologics, as do Japan’s PMDA, Brazil’s ANVISA and those of other advanced regulators.
These policies were developed independently by regulators and scientific committees in recognition of a basic fact: biologics 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—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 (BPCIA), 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 U.S. 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 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.
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
Ralph D McKibbin, MD, FACP, FACG, AGAF
Professor Philip J Schneider, MS, FASHP, FASPEN, FFIP
Andrew Spiegel, Esq
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.
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