Complying with International Pharmacopoeias

Q: We have acquired the latest versions of the United States Pharmacopeia and the European Pharmacopoeia. Is it mandatory to comply with these pharmacopoeias?

A: Pharmacopeial monographs, which are specifications and test procedures, are validated and recognized by regulators under good manufacturing practices (GMPs). In the United States, the United States Pharmacopeia (USP) defines a monograph as “a written document that reflects the quality attributes of medicines approved by the US Food and Drug Administration” that provide quality expectations and include tests and information regarding identity, strength, purity, and performance.¹

However, general information chapters offering broader guidance are generally considered advisory rather than mandatory. Companies may deviate from these recommendations but must document and justify how their alternative approach still achieves GMP compliance.

The USP is developed by a nongovernment organization; however, the European and Japanese pharmacopoeias are government-issued, making them more directly enforceable. There are other voluntary standards (eg, GAMP, ISO, ANSI, and NIST), and organizations like the Parenteral Drug Association operate within an ANSI-accredited framework, issuing technical reports where official standards don’t exist.

And the debate is whether you need to comply with those sections of the pharmacopoeias. Because those general information chapters are advice to the practitioners, discrepancies exist between the practice that people put in place in their facilities versus what the USP might say in their chapters. Because it’s a group of experts coming together and making a compromise on what might be the best practice in those USP general information chapters. Therefore, if you’re looking at those, and you deviate from the recommendations, you need to document and justify why. And that would be your proof that you are getting to GMP.

Merely citing a standard (eg, “we followed GAMP”) doesn’t guarantee compliance. There have been cases where companies claimed adherence but lacked the required documentation such as validation plans.

Adopting a compendial method still requires labs to perform their own verification, because original validation data come from the submitter (government or innovator), not the adopting lab. Variations from lab to lab, such as equipment differences (eg, high-performance liquid chromatography vs ultrahigh-performance liquid chromatography), require that labs confirm the method works on their own systems, essentially a robustness check.

One point manufacturers should consider is that some regulators (eg, the Chinese) require companies to maintain the original-language pharmacopoeia and demonstrate someone can actually read it, because translations may be inaccurate. Compendial compliance is nuanced, requiring companies to interpret regulations, verify methods locally, and document deviations rather than assume automatic compliance.

Reference

1. An overview of USP monographs. USP. Accessed August 5, 2026. https://www.usp.org/about/public-policy/overview-of-monographs