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.
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USP substances commonly used as excipients that also have uses as APIs are typically found in over-the-counter (OTC), topical,
ophthalmic products or prescription preparations with a long history of use that may precede pharmaceutical dosage-form regulations.
Excipients that also have API uses include inorganic materials such as certain sodium, magnesium, calcium or potassium salts,
and zinc oxide; and organic materials such as ethanol, mannitol, citric acid, lactic acid, lanolin, hypromellose, carboxymethyl
cellulose sodium, and paraffin and vegetable oils.
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).
