Interchangeable Biosimilar

Key facts

Legal standard

Public Health Service Act Section 351(k)(4)

First designation

Semglee (insulin glargine-yfgn), July 2021

Pharmacy substitution rules

Set by state law

Status shown in

FDA Purple Book

What is an interchangeable biosimilar?

Every interchangeable product is first a biosimilar: highly similar to a reference product, with no clinically meaningful differences. Interchangeability adds a substitution standard. The sponsor must show the product can be expected to produce the same clinical result as the reference product in any given patient.

For a product given more than once, the sponsor must also show that the safety and efficacy risk of alternating or switching between it and the reference product is no greater than the risk of staying on the reference product.

Interchangeability is not a higher grade of quality. The FDA's position is that biosimilars and interchangeable biosimilars are equally safe and effective; the designation matters for substitution at the pharmacy.

How interchangeability works in practice

The designation involves federal evidence standards and state substitution laws:

• Evidence: sponsors historically ran switching studies that alternated patients between products. In 2024 draft guidance, the FDA said such studies are generally not expected, relying instead on comparative analytical and clinical data.
• Designation: the FDA can grant interchangeability at approval or later through a supplement, and the Purple Book records the status.
• Exclusivity: the first interchangeable biosimilar for a reference product can earn a period of first interchangeable exclusivity, during which later biosimilars cannot be deemed interchangeable with that reference product.
• Substitution: state laws decide whether and how a pharmacist substitutes, and many require notifying the prescriber or keeping a record.

Why the interchangeable designation matters

The commercial effect depends on where the product is dispensed:

• Retail pharmacy products: for self-administered biologics such as insulin or adalimumab, automatic substitution can move volume without new prescriptions.
• Clinic-administered products: for infused biologics bought and given by hospitals or physician offices, the provider chooses the product directly, so the designation matters less.
• Competitive positioning: manufacturers of competing biosimilars use the designation in formulary negotiations and marketing to pharmacists.
• Policy change: the statutory distinction still exists, but FDA guidance has narrowed the evidence gap between biosimilar and interchangeable status, so check the current Purple Book entry rather than assuming a product lacks it.