This article is intended to address the ambiguity of labeling substances with USP–NF monographs that can have dual use as excipients or active pharmaceutical ingredients (APIs). When manufacturers market a substance as an API, current good manufacturing practices (CGMPs) apply and the manufacturing location must be registered with the US Food and Drug Administration as a drug-manufacturing establishment. When marketing a substance as an excipient, manufacturers may apply other appropriate GMPs such as United States Pharmacopeia (USP) General Chapter <1078>, which is aligned with the International Pharmaceuitcal Excipients Council–Pharmaceutical Quality Group's (IPEC–PQG) Good Manufacturing Practices for Pharmaceutical Excipient Guide. Although the USP designation normally is used for APIs and the National Formulary (NF) designation is generally used for excipients, there are exceptions. When a substance is labeled as USP or USP–NF without further clarification, one could assume that the substance may be used either as an API or an excipient, that the substance was manufactured according to CGMPs for APIs, and that the manufacturing facility is registered with FDA.
Excipients are sold through many supply routes, including distributors that may sell both APIs and excipients. Some distributors may have drug-establishment registration numbers because they repackage bulk APIs. When an excipient that also can be used as an API enters the distributor's supply chain labeled only as a compendial product (USP or NF), opportunities exist for the product to eventually be offered and used for an API function even though the ingredient may not have been manufactured to appropriate GMP requirements (e.g., the International Conference on Harmonization's Q7 Guideline).When USP or NF is incorporated into the label name of a product having both active and excipient uses, and the product is presented simply as a substance meeting the USP–NF monograph, the implication is that it could be used as both the active and inactive ingredient. When the manufacturer of a USP-NF substance chooses not to offer its product for use as an active ingredient, it should clearly communicate this intent by qualifying the labeling. To avoid confusion and clearly defend the decision not to register its facility, the manufacturer should indicate the product's restricted use as an excipient on its label, certificate of analysis, and marketing materials so that the purchaser is aware of the intended use for the product.
The USP General Notices section states that appropriate GMPs be used in the manufacture of USP Official Articles. The manufacturer of Official Articles labeled USP or NF must follow appropriate GMPs based on its intended market for the product. Manufacturers then may sell the ingredient into the appropriate excipient and/or API markets based upon the GMP selected. In cases where sales volume will not support a separate facility, one set of appropriate GMPs may be applied across the product line or the process may be campaigned to produce a specific grade (e.g., excipient or API) using a level of GMP appropriate for the intended use. Where these options are not practical, an ingredient manufacturer may choose a level of GMP that specifically targets the excipient use of the USP or NF article, rather than the API GMP requirements that allow for either use (API or excipient).