Active Pharmaceutical Ingredient (API)

Key facts

Defined in

21 CFR 207.1 (drug establishment registration and listing)

Regulatory synonym

Drug substance

Confidential filing

Drug Master File (DMF), usually Type II for drug substances

Substance identifier

FDA Unique Ingredient Identifier (UNII)

What is an active pharmaceutical ingredient?

A finished drug product, such as a tablet or injection, combines one or more active pharmaceutical ingredients with excipients such as fillers, binders, preservatives and coatings. The API produces the therapeutic effect; excipients make the product stable, absorbable and manufacturable.

Regulators also distinguish the active ingredient from the active moiety. Many APIs are salts or esters, such as atorvastatin calcium, while the active moiety is the core molecule responsible for the effect. New chemical entity exclusivity is judged at the active moiety level.

In pharmaceutical data, API should not be confused with an application programming interface; context usually makes the meaning clear.

How APIs are made and regulated

APIs often come from a different company and country than the finished product:

• Manufacturing: APIs are produced by chemical synthesis, fermentation or cell culture, often at facilities separate from the plant that makes the finished dosage form.
• Registration and inspection: API manufacturers serving the U.S. market, including foreign sites, must register with the FDA and follow current good manufacturing practice (CGMP).
• Drug Master Files: API makers often submit a confidential Type II DMF that finished-product applicants reference in their NDA or ANDA, protecting the API maker's trade secrets.
• User fees: API facilities referenced in generic drug applications pay annual facility fees under the Generic Drug User Fee Amendments (GDUFA).
• Volume reporting: the CARES Act of 2020 requires registrants to report annually the amount of each listed drug they manufacture.

Why APIs matter

The API is where many supply, quality and data questions start:

• Supply chain risk: API production for many generic drugs is concentrated in a few countries and sites, so one inspection failure or plant outage can contribute to shortages.
• Sourcing intelligence: DMF lists and establishment registrations show which companies can supply a given API to the U.S. market.
• Recall analysis: contamination in an API, such as the nitrosamine impurities found in valsartan in 2018, can trigger recalls across many finished products and labelers.
• Data joins: ingredient names and UNII codes link products across the NDC Directory, Orange Book, drug labels and adverse event reports, while standard NDCs mostly identify finished products.