On June 21, 2024, FDA published a draft guidance — Considerations in Demonstrating Interchangeability With a Reference Product: Update — proposing that most interchangeable biosimilars no longer need a dedicated switching study. That is a real change in practice. It is not a change in the standard. The statute still asks the same question it always has, and a sponsor still has to answer it — the draft just stops assuming a switching study is the only acceptable answer.
What actually changed
FDA's 2019 final guidance on interchangeability generally expected sponsors to include data from at least one switching study — typically alternating patients between the reference product and the proposed interchangeable product and comparing outcomes, particularly for self-administered products. The June 2024 draft revises that expectation. It says FDA generally does not intend to recommend a comparative switching study to support a demonstration of interchangeability, and that a sponsor can instead submit a scientific justification for why its existing data already meet the standard. FDA's stated rationale leans on its own experience: by the time of the draft, most of the interchangeable products it had approved had gotten there without a switching study, and the agency reported no safety signal tied to switching in that experience.
The standard didn't move
It is worth separating two things the draft guidance does not touch. First, the statutory bar: under the Biologics Price Competition and Innovation Act, an interchangeable biosimilar must be expected to produce the same clinical result as the reference product in any given patient, and, for a product administered more than once, the risk of alternating or switching between the two must be no greater than the risk of staying on the reference product. Second, FDA's authority to ask for more. The draft guidance changes what FDA expects a sponsor to submit by default — it does not change what the sponsor ultimately has to prove, and it does not take switching data off the table if FDA decides the rest of the package does not support the claim.
- The analytical similarity package carries more weight. A comparability package built for biosimilarity now has to do double duty, supporting the interchangeability argument as well.
- PK/PD, immunogenicity, and safety data fill the gap. This is the data a scientific justification leans on in place of new switching-study results.
- The justification has to be explicit. FDA's draft expects sponsors to show their reasoning against the statutory standard, not simply assert that existing data is sufficient.
- Pending BLAs can use the new approach now, carefully. The draft says an applicant with a pending BLA can submit an amendment containing the alternative assessment — worth doing only with a clear read on where that leaves a program if the draft's position shifts before finalization.
Dropping the default switching study changes what gets filed. It does not change what has to be true for FDA to agree the product is interchangeable. Why the scientific justification still has to do real work
Where sponsors get this wrong
The risk is not that sponsors keep running switching studies they no longer need — that costs time and money but not a filing. The risk runs the other way: treating the draft guidance as settled, dropping a planned switching study from the program timeline, and discovering at review that FDA was not persuaded the existing analytical, PK/PD, and immunogenicity data closed the gap on this particular molecule. A protein with a complex immunogenicity profile, a narrow therapeutic index, or thin real-world switching experience for its class is a weaker candidate for the justification-only path than the draft's framing suggests on a first read. This is a biosimilar regulatory strategy decision, not a formatting one, and it belongs in the program's CMC strategy conversation well before the interchangeability submission is drafted.
- Confirm the analytical similarity package is load-bearing. It has to carry an interchangeability argument, not just a biosimilarity one.
- Assemble the PK/PD, safety, and immunogenicity bridge. This is the data doing the work a switching study used to do.
- Draft the scientific justification memo. Write the explicit reasoning against the BPCIA standard — don't assume the data speaks for itself.
- Track the guidance's final status before you file. Build a switching-study contingency into the timeline until FDA finalizes its position.
None of this is exotic, but it is judgment-dependent in a way a checklist cannot resolve. The sponsors who come out ahead will be the ones who treat the scientific justification as the real deliverable — built early, stress-tested against the statutory standard, and ready to absorb a switching-study request if FDA still wants one — rather than the ones who read "no longer the default" as "no longer required" and found out the difference at filing.
Frequently asked questions
Does FDA still require a switching study for biosimilar interchangeability?
Not by default. FDA's June 2024 draft guidance proposes that sponsors generally will not need to conduct a dedicated switching study to support interchangeability. A sponsor can instead submit a scientific justification, built on existing analytical, nonclinical, and clinical data, explaining why the product meets the statutory interchangeability standard without new switching data. FDA can still request switching data where the existing package does not support that conclusion, and as a draft, this approach is not yet final guidance.
What replaces the switching study under the 2024 draft guidance?
A written scientific justification that draws on the product's analytical similarity data, pharmacokinetic and pharmacodynamic comparisons, immunogenicity data, and real-world safety experience with the reference product, directed at the Biologics Price Competition and Innovation Act's interchangeability standard: that the biosimilar can be expected to produce the same clinical result as the reference product in any given patient, and, for products given more than once, that alternating or switching carries no greater risk than staying on the reference product.
Can a sponsor with a pending BLA use the new approach now?
FDA's draft says applicants with a pending biologics license application can submit an amendment containing the alternative interchangeability assessment for FDA's review. Because the guidance remains in draft, sponsors should confirm its current status and FDA's position on their specific application before relying on it to drop planned switching-study work.
Sources & further reading
- FDA. Considerations in Demonstrating Interchangeability With a Reference Product: Update; Draft Guidance for Industry; Availability (89 FR 52060, June 21, 2024). federalregister.gov
- FDA. Considerations in Demonstrating Interchangeability With a Reference Product: Update — guidance document page. fda.gov
This article is provided for general informational purposes and reflects the regulatory landscape as of October 2026. It is not legal or regulatory advice. Confirm the current status of FDA's interchangeability guidance and its application to your product with FDA or qualified counsel before acting.
