Inside IPEC: Dual-Use Labeling - Pharmaceutical Technology

Latest Issue
PharmTech

Latest Issue
PharmTech Europe

Inside IPEC: Dual-Use Labeling
Clear labels for substances that can be used as excipients, APIs, or both are critical to end-product use.


Pharmaceutical Technology


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.



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).


ADVERTISEMENT

blog comments powered by Disqus
LCGC E-mail Newsletters

Subscribe: Click to learn more about the newsletter
| Weekly
| Monthly
|Monthly
| Weekly

Survey
FDASIA was signed into law two years ago. Where has the most progress been made in implementation?
Reducing drug shortages
Breakthrough designations
Protecting the supply chain
Expedited reviews of drug submissions
More stakeholder involvement
Reducing drug shortages
29%
Breakthrough designations
10%
Protecting the supply chain
43%
Expedited reviews of drug submissions
10%
More stakeholder involvement
10%
View Results
Jim Miller Outsourcing Outlook Jim Miller Health Systems Raise the Bar on Reimbursing New Drugs
Cynthia Challener, PhD Ingredients Insider Cynthia ChallenerThe Mainstreaming of Continuous Flow API Synthesis
Jill Wechsler Regulatory Watch Jill Wechsler Industry Seeks Clearer Standards for Track and Trace
Siegfried Schmitt Ask the Expert Siegfried SchmittData Integrity
Sandoz Wins Biosimilar Filing Race
NIH Translational Research Partnership Yields Promising Therapy
Clusters set to benefit from improved funding climate but IP rights are even more critical
Supplier Audit Program Marks Progress
FDA, Drug Companies Struggle with Compassionate Use Requests
Source: Pharmaceutical Technology,
Click here