Biologic

Key facts

Legal basis

Public Health Service Act Section 351 (42 U.S.C. 262)

Application type

Biologics License Application (BLA)

FDA review centers

CDER (most therapeutic proteins) and CBER (vaccines, blood, cell and gene therapy)

Reference product exclusivity

12 years from first licensure, under the BPCI Act of 2009

Listed in

FDA Purple Book

What is a biologic?

Biologics are large, complex products made in or derived from living systems such as bacteria, yeast or mammalian cells. The category includes therapeutic proteins and monoclonal antibodies, vaccines, blood and blood components, allergenic extracts, and cellular and gene therapies.

Because living cells produce them, biologics are sensitive to manufacturing conditions, and a second manufacturer cannot make an exact copy the way chemists can reproduce a small-molecule drug. That is why follow-on biologics are called biosimilars rather than generics.

The legal line is set by statute and regulation. Since March 23, 2020, certain proteins once approved as drugs, including insulins and human growth hormone, have been deemed licensed biologics. A protein for this purpose is an amino acid polymer of more than 40 amino acids; shorter peptides remain regulated as drugs.

How biologics are regulated

Biologics follow a licensing framework separate from the one used for chemical drugs:

• Licensure: sponsors submit a Biologics License Application (BLA) under Section 351(a) showing the product is safe, pure and potent.
• Review: the Center for Drug Evaluation and Research (CDER) reviews most therapeutic proteins and monoclonal antibodies; the Center for Biologics Evaluation and Research (CBER) reviews vaccines, blood products and cell and gene therapies.
• Exclusivity: the Biologics Price Competition and Innovation Act of 2009 (BPCI Act) gives a reference product 12 years of exclusivity from first licensure, and no biosimilar application may be submitted until 4 years after that date.
• Follow-on products: biosimilars and interchangeable biosimilars are licensed through the abbreviated Section 351(k) pathway.
• Listing: licensed biologics, their exclusivity dates and biosimilar relationships appear in the Purple Book.

Why biologics matter

Biologics behave differently from small-molecule drugs in pricing, payment and data:

• Forecasting: many of the highest-spend products in Medicare and commercial plans are biologics, so their exclusivity and patent expiry dates anchor biosimilar forecasts.
• Benefit design: many biologics are infused or injected in a clinic, so Medicare pays for them under Part B, generally at average sales price plus 6 percent, billed with HCPCS codes rather than pharmacy claims.
• Price negotiation: under the Inflation Reduction Act, biologics become eligible for Medicare price negotiation 11 years after licensure, compared with 7 years after approval for small-molecule drugs.
• Data joins: one biologic may carry a BLA number, several NDCs and a HCPCS code, and a four-letter suffix on newer nonproprietary names, such as adalimumab-atto, separates products that share a molecule.