An Active Pharmaceutical Ingredient (API) is the substance responsible for the pharmacological activity or other direct effect of a medicinal product. Its identity, quality, purity and manufacturin controls are fundamental to the quality, safety and efficacy of the finished product. Regulatory frameworks use closely related terms, including Active Substance and Drug Substance.
Definition and Regulatory Context
In pharmaceutical manufacturing, an Active Pharmaceutical Ingredient is the substance or mixture of substances that becomes the active component of a medicinal product and provides its intended pharmacological activity or other direct effect.
The term is widely used in international GMP guidelines and regulatory documentation. Depending on the jurisdiction and document, the same or a closely related concept may be referred to as an Active Substance or a Drug Substance. The precise wording and scope should therefore be considered in the context of the applicable regulatory framework.
Official Definitions and Regulatory Sources
1. International Council for Harmonisation (ICH) — Active Pharmaceutical Ingredient (API) or Drug Substance
Source: ICH Q7 — Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
Reference: Glossary
ICH defines an Active Pharmaceutical Ingredient (API), also referred to as a Drug Substance, as any substance or mixture of substances intended to be used in the manufacture of a drug (medicinal) product and that, when used in production, becomes an active ingredient of the drug product. Such substances are intended to furnish pharmacological activity or another direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease, or to affect the structure and function of the body.
ICH Q7 also defines an API Starting Material as a raw material, intermediate or API used in the production of an API and incorporated as a significant structural fragment into its structure. This is a separate term and should not be confused with the API itself.
Official source: ICH Q7 — Good Manufacturing Practice for Active Pharmaceutical Ingredients
2. Eurasian Economic Union — Active Pharmaceutical Ingredient
Source: Good Manufacturing Practice Rules of the Eurasian Economic Union
Reference: Section 20, “Terms and Definitions”, Decision of the Council of the Eurasian Economic Commission No. 77 of 3 November 2016, as amended
The EAEU GMP Rules define an Active Pharmaceutical Ingredient (API) as a substance or mixture of substances used in the manufacture of a medicinal product which, during the manufacturing process, becomes its active ingredient.
Such substances have pharmacological or other direct effects and are intended for the treatment, diagnosis or prevention of diseases, care, treatment and relief of symptoms, or to affect the structures or physiological functions of the body.
Official source: Eurasian Economic Commission — Legal Acts
3. Eurasian Economic Union — Active Pharmaceutical Ingredient in the Pharmacopoeia
Source: Pharmacopoeia of the Eurasian Economic Union
Reference: General Notices, Section 1.1, General Provisions
The Pharmacopoeia of the EAEU defines an Active Pharmaceutical Ingredient as a substance for pharmaceutical use containing active ingredient(s) of chemical, plant, animal or human origin.
The Pharmacopoeia also distinguishes an API from an excipient. An excipient is a substance for pharmaceutical use that is not an active substance in the given medicinal product and is intended to create a dosage form with specific properties.
Official source: Pharmacopoeia of the Eurasian Economic Union — Decision of the EEC Board No. 100 of 11 August 2020
4. European Union — Active Pharmaceutical Ingredient / Active Substance
Source: EudraGMDP Glossary, European Medicines Agency
The EudraGMDP Glossary describes an Active Pharmaceutical Ingredient as any substance or mixture of substances intended for use in the manufacture of a medicinal product which, when used in production, becomes an active ingredient of that product. Such substances are intended to provide pharmacological activity or another direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease, or to affect the structure and function of the body.
The glossary treats Active Substance and API as equivalent terms in this context.
Terminological note: The EU pharmaceutical legislation in Directive 2001/83/EC defines the broader term substance, but does not provide a separate definition of API in Article 1. The EudraGMDP glossary and EU GMP framework provide the more directly relevant terminology for API manufacturing and supervision.
Official sources:
- EudraGMDP Glossary — European Medicines Agency
- EudraLex Volume 4 — EU Guidelines for Good Manufacturing Practice
5. United States — Active Pharmaceutical Ingredient
Source: US Food and Drug Administration (FDA), GDUFA Glossary
The FDA GDUFA Glossary defines an Active Pharmaceutical Ingredient as:
- a substance, or a mixture where the substance is unstable or cannot be transported on its own, intended to be used as a component of a drug and to furnish pharmacological activity or another direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease, or to affect the structure or any function of the human body; or
- a substance intended for final crystallisation, purification or salt formation, or a combination of these activities, to become the final API described above.
This definition includes certain materials undergoing final processing to become the API. It is provided in the context of the FDA’s Generic Drug User Fee Amendments (GDUFA) programme.
Official source: FDA — GDUFA Glossary
Related Terminology in International Regulatory Frameworks
Several terms are used in regulatory documents to describe the active substance incorporated into a medicinal product. Although they are closely related, their use reflects the terminology and scope of the relevant framework.
- Active Pharmaceutical Ingredient (API): The widely used term in ICH guidelines, EAEU GMP Rules and pharmaceutical manufacturing documentation.
- Active Substance: A term used in the EU regulatory framework and commonly treated as equivalent to API in GMP documentation.
- Drug Substance: The term used alongside API in ICH Q7 and widely used in US pharmaceutical regulatory documentation.
- API Starting Material: A raw material, intermediate or API used in the production of an API and incorporated as a significant structural fragment into its structure. It is not the same as the finished API.
- Excipient: A substance used in the formulation of a medicinal product that is not the active substance responsible for its pharmacological effect.
Regulatory Significance
APIs are subject to specific regulatory requirements throughout their manufacture, testing, storage and distribution. Their quality directly affects the quality of the finished medicinal product.
Key regulatory areas include:
- Good Manufacturing Practice: API manufacturing must comply with applicable GMP requirements, including ICH Q7 and relevant regional GMP rules.
- Quality and purity: APIs must meet established specifications for identity, assay, impurities and other relevant quality attributes.
- Manufacturing process control: Production processes, critical steps and changes must be appropriately controlled and documented.
- Stability and storage: Stability data and appropriate storage conditions are required to maintain API quality throughout its intended period of use.
- Regulatory documentation: Information on API manufacture, control and stability forms part of the pharmaceutical quality documentation submitted in support of medicinal product registration.
- Supply chain oversight: Manufacturers and regulatory authorities need appropriate traceability of API sources, manufacturing sites and batches.
Editorial Note
The definitions in this entry are taken from the cited regulatory and pharmacopoeial sources. The terms Active Pharmaceutical Ingredient, Active Substance and Drug Substance are closely related and are often used interchangeably in pharmaceutical practice. Their exact regulatory meaning should nevertheless be determined by reference to the applicable legislation, GMP guideline or pharmacopoeial text.
