In order to receive FDA approval to market a new drug in the United States, Sponsors must submit either a New Drug Application (NDA) or a Biologics License Application (BLA). BLAs are for biological products while NDAs are for small molecule drugs.

In June 1938 President Roosevelt signed the Federal Food, Drug and Cosmetic Act into law, which required new drugs to be tested for safety before marketing. The results of the tests would be submitted to the FDA in a NDA.¹ 

The Drug Price Competition and Patent Term Restoration Act of 1984 expedited FDA review of generic versions of brand name drugs without repeating efficacy and safety data.¹

The Biologics Price Competition and Innovation (BPCI) Act introduced an abbreviated approval pathway for biosimilars and mandated that all biological products must be submitted for marketing approval through a BLA, and not an NDA. The BPCI Act took effect March 2020.²

The first comprehensive federal consumer protection law was the 1906 Food and Drugs Act, which prohibited misbranded and adulterated food and drugs in interstate commerce. However, the act had shortcomings and many hazardous consumer items remained on the market legally. In 1937, when an untested pharmaceutical killed scores of patients, including many children, as soon as it went on the market. The Food, Drug, and Cosmetic Act tightened controls over drugs and food and included new consumer protection against unlawful cosmetics and medical devices.³

An NDA and BLA consists of data and information about the drug as gained through its development, as well as a summary of formulation and manufacturing processes, and proposed labeling information to be included in the drug’s packaging. In general, both applications should contain enough data on the product's safety and efficacy for its proposed use, and if the drug product is manufactured in a way that preserves its identity, strength, quality, and purity. Drugs that are approved via an NDA pathway are regulated under Section 505 of the Food, Drug, & Cosmetics (FD&C) Act. All biological products must be approved through the BLA pathway, and are licensed under Section 351 of the Public Health Service Act, in addition to being regulated by the FD&C Act.²

Due to the complexities of manufacturing biological products, a pre-license inspection of the facility is generally required before a BLA is approved. Pre-approval inspections sometimes also take place during an NDA review, but are typically conducted based on risk assessment by the Agency. There are two Centers within the FDA that are responsible for the review and approval of drug marketing applications and general regulatory oversight: the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research (CBER). All drug products are regulated by CDER, biological products can be regulated by either CDER or CBER.²

There are over 20,000 prescription drug products approved for marketing and about 300 FDA-licensed biologics products.⁴

The biological product categories that are reviewed by CDER instead of CBER are: monoclonal antibodies for in vivo use, most proteins for therapeutic use (e.g., cytokines, enzymes, and other novel proteins except those assigned to CBER, such as vaccines and blood products), immunomodulators, and growth factors.²

1. A Brief History of CDER. U.S. Food and Drug Administration. https://www.fda.gov/about-fda/fda-history-exhibits/brief-history-center-drug-evaluation-and-research. Published 2018. 

2. Alabanza A. What are the Regulatory Differences Between an NDA and BLA?. Nuventra.com. https://www.nuventra.com/resources/blog/regulatory-differences-between-an-nda-bla/. Published 2020.

3. How did the Federal Food, Drug, and Cosmetic Act come about?. U.S. Food and Drug Administration. https://www.fda.gov/about-fda/fda-basics/how-did-federal-food-drug-and-cosmetic-act-come-about. Published 2018. 

4. Fact Sheet: FDA at a Glance. U.S. Food and Drug Administration. https://www.fda.gov/about-fda/fda-basics/fact-sheet-fda-glance. Published 2020.