Substituting a chemically identical generic for a brand drug is second nature for pharmacists. Substituting an interchangeable biosimilar is not the same act, even though it can feel like it — and most states impose notification, documentation, or interchangeability-designation requirements on biosimilar substitution that don’t apply to traditional generic substitution at all. Getting this wrong is an easy way to draw board attention over what was otherwise a clinically reasonable decision.
Why biosimilar substitution is treated differently
The FDA designates biosimilars in two tiers: a biosimilar is approved as highly similar to its reference product, while an interchangeable biosimilar has additionally demonstrated it can be expected to produce the same clinical result as the reference product in any given patient, including through repeated switching. Only interchangeable biosimilars can generally be substituted at the pharmacy level without prescriber authorization — a plain biosimilar (non-interchangeable) still requires the prescriber to specifically prescribe or authorize that product.
Nearly every state has passed its own biosimilar substitution statute, layered on top of the FDA interchangeability framework, because pharmacy substitution authority is a matter of state law even when the underlying interchangeability determination is federal. That’s the same structural pattern seen in hormonal contraceptive prescribing by state laws — federal approval sets the ceiling, state law determines what a pharmacist can actually do with it.
The common elements across state biosimilar substitution laws
Most state statutes share a similar structure, though specifics vary meaningfully:
Interchangeable designation required — The overwhelming majority of states permit substitution only for FDA-designated interchangeable biosimilars, not all biosimilars generally. A pharmacist substituting a merely-biosimilar (non-interchangeable) product without prescriber sign-off is acting outside dispensing authority in most states.
Prescriber notification — This is where states diverge most. Many states require the pharmacist to notify the prescriber of the substitution, typically within a set window (commonly 3-5 business days) after dispensing. Some states waive notification if the prescriber has already indicated substitution is acceptable, or if the notification is transmitted automatically through an EHR/pharmacy interoperability system. A smaller number of states have dropped the notification requirement entirely, treating interchangeable biosimilar substitution the same as generic substitution.
Patient notification — Most states also require informing the patient (or their agent) that a substitution was made, often satisfied by standard counseling documentation.
Recordkeeping — States generally require the pharmacy to retain a record of the substitution, including the specific product dispensed, for a set retention period — commonly matching the state’s general prescription record retention rule.
Publicly available substitution list — Some states maintain or reference a state-published list of substitutable interchangeable biosimilars, separate from the FDA’s Purple Book, and pharmacists are expected to check state guidance rather than assume FDA designation alone is sufficient.
Where this intersects with prescriptive authority expansion
As pharmacist prescriptive authority continues to expand in many states, some biosimilar categories — particularly self-administered specialty products — are increasingly relevant to pharmacists exercising broader prescribing or therapy management authority, not just substitution. Our pharmacist prescriptive authority expanding guide and collaborative practice agreements by state post both cover adjacent authority that can affect how a pharmacist manages a patient’s biosimilar therapy beyond simple substitution.
Biosimilar substitution also comes up frequently in specialty pharmacy and 340B settings, where product selection intersects with contract and formulary requirements — see our 340B program compliance guide for how covered entities handle product-level tracking.
Practical steps before substituting
- Confirm interchangeable designation status in the FDA Purple Book — not just biosimilar approval status
- Check your state’s specific notification timeline and method (fax, EHR message, phone) before dispensing
- Document the substitution in the patient record per your state’s retention rule
- Confirm whether your state requires the substitution to be flagged on the label or receipt
Biosimilar substitution laws are one of the more actively legislated areas of pharmacy practice right now, with several states amending notification and documentation requirements in recent sessions. Always verify current requirements with your state board of pharmacy before relying on general summaries, including this one.
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Related state profiles: California pharmacist requirements, New York pharmacist requirements, Texas pharmacist requirements.