Biosimilar

Key facts

Approval pathway

Section 351(k) of the Public Health Service Act

Created by

Biologics Price Competition and Innovation Act of 2009

First U.S. approval

Zarxio (filgrastim-sndz), March 2015

Naming convention

Nonproprietary name plus a four-letter suffix, such as adalimumab-atto

Listed in

FDA Purple Book

What is a biosimilar?

A biosimilar is the biologic counterpart of a generic drug, but the legal standard is different. Because biologics are made in living cells and cannot be copied exactly, a biosimilar sponsor shows that its product is highly similar to the reference product, notwithstanding minor differences in clinically inactive components, and that there are no clinically meaningful differences in safety, purity or potency.

A biosimilar must share the mechanism of action (to the extent it is known), route of administration, dosage form and strength of its reference product, and it can only be licensed for conditions of use the reference product already holds. A sponsor may seek fewer indications than the reference product.

How biosimilar approval works

An application cannot be submitted until 4 years after the reference product was first licensed, and cannot be approved until 12 years after. Patent disputes, often run through the BPCI Act information exchange known as the patent dance, frequently delay launch further.

A Section 351(k) application relies on the FDA's earlier finding for the reference product and builds a totality-of-the-evidence case from:

• Analytical studies comparing structure and function, which form the foundation of the application.
• Clinical pharmacology studies comparing pharmacokinetics and, where relevant, pharmacodynamics.
• An immunogenicity assessment comparing immune responses to the two products.
• Comparative clinical efficacy studies when uncertainty remains, although the FDA has moved toward requiring them less often.

Why biosimilars matter

Biosimilar entry is the main source of price competition for biologics:

• Forecasting: biosimilar launch dates for high-spend biologics drive payer savings estimates and reference product revenue models.
• Medicare Part B payment: a biosimilar is paid at its own average sales price plus 6 percent of the reference product's average sales price, and the Inflation Reduction Act temporarily raised the add-on to 8 percent for qualifying biosimilars.
• Claims tracking: each biosimilar has its own HCPCS code, so uptake can be measured separately from the reference product in Medicare claims.
• Formulary placement: payers and pharmacy benefit managers can prefer a biosimilar over its reference product, so formulary decisions often matter more than launch date.

Biosimilar vs generic drug

A generic must contain an identical active ingredient and show bioequivalence, usually with a modest data package. A biosimilar only needs to be highly similar and is supported by a larger analytical and clinical program. Pharmacy-level substitution without the prescriber applies to therapeutically equivalent generics and, for biologics, only to biosimilars the FDA has designated interchangeable, subject to state law.