FDA biosimilars: the approved biosimilar and interchangeable list

A biosimilar is a biological product that is highly similar to, and has no clinically meaningful differences from, an already-FDA-approved reference biologic. Biosimilars are licensed under the abbreviated 351(k) pathway of the Public Health Service Act, which lets a sponsor rely on FDA’s prior finding of safety and effectiveness for the reference product instead of repeating the full clinical program. Every biosimilar approved by FDA is listed in the Purple Book, the official database of licensed biological products.

All interchangeables are biosimilars, but not all biosimilars are interchangeable. An interchangeable biosimilar carries an additional designation under 351(k)(4), which means a pharmacist may substitute it for the reference product without consulting the prescriber, subject to state law. Interchangeability is a substitution status, not a statement that the product is safer or more effective. FDA has signaled it intends to streamline the separate interchangeability data expectations, so the practical line between the two is narrowing.

A reference (351(a)) biologic carries 12 years of reference-product exclusivity from first licensure, and a biosimilar application cannot be submitted until 4 years after that date. Beyond exclusivity, BLA holders publish the patents exchanged in the statutory "patent dance" under the Biological Product Patent Transparency Act — you can review those on each product record. The first interchangeable for a reference product can also earn its own period of exclusivity. Use the Purple Book tool to track when each reference product’s protection lapses and which follow-ons are queued behind it.

Generics are exact chemical copies of small-molecule drugs and live in the Orange Book under the ANDA pathway. Biosimilars are not identical copies — biologics are large, complex molecules produced in living systems, so a biosimilar is "highly similar" rather than identical, and is approved under 351(k) and listed in the Purple Book. If you are looking for small-molecule generics, therapeutic-equivalence codes, and drug patents, use the FDA Orange Book tool instead.