USP and global regulators collaborate

U.S. FDA and many international regulators rely on USP standards and science-based solutions – including those for impurities – for drug approvals and post-market surveillance.

USP, U.S. FDA and global regulators collaborate to jointly drive solutions towards our shared commitment to medicine quality. Over 200 U.S. FDA staff serve on USP Expert Committees and Panels responsible for scientific development of USP standards, including impurity limits.

Under U.S. law, drug products marketed in the U.S. are expected to meet quality specifications in more than 4000 monograph standards in USP-NF, including tests for impurities using 1,500 impurity Reference Standards available from USP.

Our growing catalog of impurities and reference standards

In addition to official USP Pharmacopeial Reference Standards for impurities, we now offer a growing catalog of impurities through our Pharmaceutical Analytical Impurities (PAI) product line which included new nitrosamine drug substance-related impurities (NSDRIs).

We have released new nitrosamine Pharmaceutical Analytical Impurities (PAIs) to support manufacturers’ development of analytical methods that can identify and control these impurities in drug products.

Carcinogenic nitrosamine impurities in some commonly prescribed drugs have prompted multiple product recalls. In silico analysis on more than 12,000 Active Pharmaceutical Ingredients (APIs) and API-related impurities led USP and industry scientists to conclude that approximately 40% of APIs and 30% of API impurities listed in the Global Substance Registration System are potential nitrosamine precursors and vulnerable to nitrosamine formation under certain conditions.

Manufacturers are grappling with how best to assess and mitigate the risk of simple nitrosamines and more complex nitrosamine drug substance related impurities (NDSRIs). As manufacturers conduct confirmatory tests and report changes in nitrosamine mitigation strategies to regulators, they are encouraged to develop control strategies and design approaches that reduce NDSRIs to acceptable levels if detected in drug products at objectionable levels. Suitable analytical methods for mitigating nitrosamine risk require trustworthy impurity sources, and few NDSRIs are readily available to manufacturers.

Spotting impurities with PAIs for impurities referenced in USP-NF Monographs can help strengthen R&D and produce quality medicines. Impurity profiling has become an important activity in ensuring high-quality of drugs. USP-NF Monographs include methods to test for multiple types of impurities including process-related and degradation impurities in drugs. Impurity tables, when listed in monographs, feature relative retention time, relative response factor and acceptance criteria (NMT%) for listed impurities which, combined with USP Reference Standards and USP Pharmaceutical Analytical Impurities (PAIs), helps accurate profiling. Through USP’s PAI portfolio, impurities referenced in USP-NF Monographs are more accessible than ever with a wide range of availability.

USP’s catalog of Pharmaceutical Analytical Impurities is growing rapidly. Please tell us about the APIs for which available impurities would have the most benefit to your work. Connect with your USP Account Manager or email us at PAI@usp.org