FDA Active Pharmaceutical Ingredient (API) Process Inspection Guidelines
BACKGROUND
GENERAL
APIs are subject to the adulteration provisions of Section 501(a)(2)(B) of the Act, which requires all drugs to be manufactured in conformance with CGMP. No distinction is made between an API and a finished pharmaceutical in the Act and the failure of either to comply with CGMP constitutes a violation of the Act. FDA has not promulgated CGMP regulations specifically for APIs or drug components (as we have for finished pharmaceuticals). Thus, the use of “CGMP” in this document refers to the requirements of the Act rather than the requirements of 21 CFR Parts 210 and 211 regulations for finished pharmaceuticals.
FDA has long recognized that the CGMP requirements in the good manufacturing practice regulations for finished pharmaceuticals (21 CFR Parts 210 and 211) are valid and applicable in concept to active pharmaceutical ingredient (API) manufacturing. These concepts include, among others, building quality into the drug by using suitable equipment and employing appropriately qualified and trained personnel, establishing adequate written procedures and controls designed to assure manufacturing processes and controls are valid, establishing a system of in-process material and final drug tests, and ensuring stability of drugs for their intended period of use. In 2001, FDA adopted an internationally harmonized guidance to industry on API CGMPs in conjunction with regulatory partners in the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). This guidance is ICH Q7, Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients. ICH Q7 represents the Food and Drug Administration’s (FDA’s) current thinking on CGMPs for API’s. Thus, API and related manufacturing and testing facilities that follow this guidance generally will be considered to comply with the statutory CGMP requirement. However, alternate approaches may be used if such approaches satisfy the requirements of Section 501(a)(2)(B) of the Act as long as the approach ensure that the API meets its purported or represented purity, identity, and quality characteristics.
The term “active pharmaceutical ingredient” (API) is used in this program consistent with the meaning of this term as defined in ICH Q7. An active pharmaceutical ingredient is defined in ICH Q7 as “any substance or mixture of substances intended to be used in the manufacture of a drug product and that, when used in the production of a drug, becomes an active ingredient in the drug product. Such substances are intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment or prevention of disease or to affect the structure and function of the body.” Currently, other terms are also used by FDA and industry to mean an API. “Drug substance” and “bulk pharmaceutical chemical” (BPC) are terms commonly used to mean API and, for BPC, inactive ingredients. The use of these terms to describe active ingredients may be considered equivalent to the term used here, API.
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FDA Active Pharmaceutical Ingredient (API) Process Inspection Guidelines
FDA Active Pharmaceutical Ingredient (API) Process Inspection:
