Using Compendial-Grade Materials for 503B Compounding Facilities

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Q: I work for a 503B compounding organization. A customer has asked us to manufacture a drug product that includes a food-grade component because it is less expensive than the compendial-grade material. Is this an acceptable substitution?

A: No. Substituting a food-grade material when a compendial material is available is not acceptable. US 21 United States Code (USC) 351 states that a drug is considered adulterated if it “purports to be or is represented as a drug the name of which is recognized in an official compendium, and its strength differs from, or its quality or purity falls below, the standard set forth in such compendium” (1). This section of the USC goes on to state, “No drug defined in an official compendium shall be deemed to be adulterated under this paragraph because it differs from the standard of strength, quality, or purity therefore set forth in such compendium, if its difference in strength, quality, or purity from such standard is plainly stated on its label.”

This is supported in the language contained in the General Notices of the United States Pharmacopeia (USP) (2), which states, “The USP and NF [National Formulary] are recognized in the laws and regulations of many countries throughout the world.” It also states, “In the United States under the Federal Food, Drug, and Cosmetic Act (FDCA), both USP and NF are recognized as official compendia. A drug with a name recognized in USP–NF must comply with compendial identity standards or be deemed adulterated, misbranded, or both. See, e.g., FDCA § 501(b) and 502(e)(3)(b); also US Food and Drug Administration (FDA) regulations, 21 CFR [Code of Federal Regulations] § 299.5(a&b). To avoid being deemed adulterated, such drugs must also comply with compendial standards for strength, quality, and purity, unless labeled to show all respects in which the drug differs. See, e.g., FDCA § 501(b) and 21 CFR § 299.5(c).”The General Notices goes on to state, “Compounded preparations, including drug products compounded by outsourcing facilities, may also be subject to applicable monographs” (2).

However, there may be situations where there is no compendial standard for the material you are being asked to use in the formulation. In that case, you need to perform an assessment that would allow you to introduce the material. However, before you go through the activity of introducing a non-compendial material into your facility, it is advisable to check to see if the material in question is supported by monograph requirements contained in either the European or Japanese pharmacopoeias. If neither of those compendia contain a monograph, the following questions may help you determine if the material in question is safe to bring into your facility:

• How are you going to accept this material and bring it into your facility?
• Because it is food grade, are there additional specifications you need to have based on the intended use of the finished drug product?
• Are there additional tests you need to conduct? If so, then talk to the supplier. You must work with supplier to establish the conditions, criteria, specifications, under which you will accept this material and make sure the additional criteria are included on the Certificate of Analysis.
• Determine what type of additional training needs to be conducted so you are assured you can perform the test methods for the new material.
• Determine if the cleaning procedures are effective. Is there cross-contamination to consider for the new component?

Having a robust quality management system will help you to answer these questions. You should be able to understand the risks and how to obtain information on how to sample/store the material. All of this will be in your quality management system which will allow you to have a risk management plan.

References

1. 21 USC 351: Adulterated Drugs and Devices. Title 21 Food and Drugs. Updated Sept. 16, 2024.
2. USP. General Notices and Requirements. USP-NF Dec. 1,
   2022.

About the author

Susan J. Schniepp is a distinguished fellow at Regulatory Compliance Associates.

Article details

BioPharm International®
Vol. 37, No. 9
October 2024
Page: 34

Citation

When referring to this article, please cite it as Schniepp, S.J. Using Compendial-Grade Materials for 503B Compounding Facilities. BioPharm International 2024 37 (9).