Nitrosamine Impurities: Latest USP Tool Further Aids Understanding and Control

USP has launched the newest tool in their suite of solutions to address the evolving nitrosamines crisis: the Nitrosamines Analytical Hub, a public, web-based repository of downloadable analytical procedures to test for nitrosamine impurities and related substances in pharmaceuticals.

In recent years, multiple recalls due to nitrosamine impurities (including nitrosamine drug-related impurities – NDSRI) found in medicines have made headlines due to the potential cancer risks of exposure to nitrosamines at certain levels. The complexity of the threat stems in part from the fact that pharmaceutical impurities can potentially form in a variety of ways during the life cycle of a drug’s development and manufacture. Product recalls due to the discovery of nitrosamine impurities could lead to medicine shortages and undermine patient trust in medicines.

Since the threat of nitrosamines first emerged, USP has developed standards and solutions to help regulators, manufacturers and other stakeholders better understand nitrosamine impurities, how to control them and how to mitigate the risks. USP has published a general chapter in USP-NF, General Chapter <1469> Nitrosamine Impurities, and offers eight USP Nitrosamine Reference Standards. In February 2023, in collaboration with Indian Pharmaceutical Alliance (IPA), USP hosted a workshop in India on a range of topics from sources of nitrosamines to analytical considerations, toxicity assessment and regulatory compliance.

Their latest offering, the new Analytical Hub, is housed within USP’s Nitrosamines Exchange. The procedures published in it are curated by USP’s science staff through internal development and validation or through scientific review of donated materials. The procedures published in the Hub are complementary tools to USP’s official standards that can be of great benefit to those trying to understand and control for nitrosamines impurities that may arise throughout a product’s life cycle.

The Analytical Hub features user-friendly navigation, is searchable and highlights key analytical procedure parameters and chromatograms. The application notes can be downloaded in PDF format and contain all the information needed to run, process and report the analysis described in the note. USP recently published the first application note in the Analytical Hub on a chromatography procedure for nitrosamines quantification in solvents by GC-MS/MS. These solvents (Dichloromethane, Ethylacetate, Toluene and o-Xylene) commonly used in active synthesis, have been found in instances to be contaminated with nitrosamines during shipment or transfer between storage vessels. New application notes will periodically be uploaded as they are available. Under development is a note covering another procedure for N-nitrosodimethylamine (NDMA) analysis in ranitidine products.

The Analytical Hub offers the opportunity for real-time information sharing that can help fill gaps in users’ knowledge about how nitrosamine impurities form and which analytical methods are most suitable for specific products. Access to this type of information can be critical for addressing problems efficiently and agilely.

The Analytical Hub launch is an exciting milestone in the ongoing story of the Nitrosamines Exchange, a unique online community hosted by USP since spring 2021 with a rapidly growing audience of users interested in sharing knowledge and solutions related to controlling nitrosamines in medicines. Ongoing research is adding to our collective understanding of nitrosamines and how they form. Keeping up with the developing science can be a significant challenge. The Nitrosamines Exchange and its new Analytical Hub offer unique opportunities to share information in real-time and surface new findings or questions as they emerge.

The Exchange and Analytical Hub are just the latest examples of a kind of collaborative approach to manufacturing challenges that has increasingly been embraced by stakeholders, particularly amid the COVID-19 pandemic, which transcended borders and required global solutions. The threats to the global medicines supply chain posed by impurities are too great for any single organization to take on alone, and USP is proud to provide resources to help meet the challenge.

The Exchange was launched less than two years ago but has already yielded collaborative research, problem-solving and relationship-building. Members represent more than 80 different countries, and the Exchange has seen active conversations in English, Japanese, Mandarin, Portuguese and Spanish. This is a truly exciting forum for all of us working to solve this problem facing the pharmaceutical industry to continue to ensure quality and enable trust in our medicines.

We invite you to get involved! Membership in the Exchange is free and open to the public. If you are interested in donating an analytical method to the Hub, collaborating with USP for the development of a novel method or inquiring about specific analytical methods needs or a particular nitrosamine impurity chemical substance, please visit the Nitrosamines Exchange today.

FOOTNOTE: The procedures contained in the application notes should be validated by the user. USP is not responsible for use or implementation of the procedures.

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Source: USP, Nitrosamine Impurities: Latest USP Tool Further Aids Understanding and Control

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