Biologics License Application (BLA)

Key facts

Legal basis

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

Regulations

21 CFR Part 601 and related parts 600 to 680

Approval standard

The product is safe, pure and potent

Reviewed by

CBER or CDER, depending on the product class

Abbreviated route

Section 351(k), for biosimilar and interchangeable products

What is a Biologics License Application?

Biologics are large, complex products made in or derived from living systems, so small manufacturing changes can alter the final product. A BLA therefore covers both clinical evidence and detailed information about the manufacturing process and facilities. An approved BLA results in a U.S. license for the product.

The standard under Section 351(a) is that the product is safe, pure and potent, which in practice calls for clinical evidence comparable to what a New Drug Application (NDA) needs. Original BLAs pay fees under the Prescription Drug User Fee Act (PDUFA) and share its review time goals.

How the BLA framework is divided

Four distinctions shape how a biologic is reviewed and tracked:

• Section 351(a) BLA: a full, stand-alone application for an original, or reference, biological product.
• Section 351(k) BLA: an abbreviated application for a biosimilar or interchangeable product, created by the Biologics Price Competition and Innovation Act (BPCIA).
• CDER vs CBER: CDER reviews most therapeutic proteins and monoclonal antibodies; CBER reviews vaccines, blood products, and cell and gene therapies.
• Transition products: on March 23, 2020, certain proteins such as insulins and human growth hormone that had been approved under NDAs were deemed to be BLAs.

Why the BLA matters

The NDA vs BLA line decides which rules apply for the rest of a product's life. Biologics receive 12 years of reference product exclusivity rather than 5-year new chemical entity exclusivity, appear in the Purple Book rather than the Orange Book, and face biosimilar competition rather than ANDA generics.

For analysts, this changes how to model erosion. Biosimilar uptake depends on payer formularies, rebates and state substitution laws, so price declines after a biologic loses exclusivity have often been more gradual than the steep generic cliffs typical of small-molecule drugs.