Nitrosamine Impurities: Risk Assessment and Control Training

About this course

Why nitrosamines matter to your job

Since NDMA was found in valsartan in 2018, nitrosamines have moved from a specialist chemistry question to a routine regulatory expectation. FDA requested the withdrawal of all ranitidine products in April 2020, and certain lots of extended-release metformin were recalled the same year. Warning letters to API makers have cited weak investigations, recovered solvents and contaminated equipment. For any company that makes or holds authorisations for medicines in the US or the EU, a nitrosamine file that cannot be defended is a risk to supply, to approvals and to patients. Routine purity tests are unlikely to find these impurities, so they have to be looked for on purpose. The expectations also keep moving: FDA published its approach to less-than-lifetime limits in September 2026, and EMA revised its questions and answers again in November 2026, so a file that was complete two years ago may already be out of date.

What this course does differently

The course is built on the documents that regulators use today: FDA's guidance in its September 2024 revision, FDA's current acceptable intake limits page, and the EMA questions and answers in revision 24. Each rule is explained in plain words, with its source and date on screen, and the course states clearly where the US and the EU differ, for example where a category limit is not the same in both regions. Every module follows one built company, JKL Pharma, through a real file: the route review, supplier checks, excipients and packaging, limit calculations, NDSRI screening, confirmatory testing, results, controls and changes. Common mistakes are set beside good practice, and four practice exercises let learners do the calculations and decisions themselves. Two classes of impurity are covered with equal care: small nitrosamines such as NDMA, and nitrosamine drug substance-related impurities, including how the carcinogenic potency categorisation approach assigns a limit when no compound-specific value exists. Real cases from FDA warning letters and recalls show what inspectors and assessors look for, and why a missing listing is a question rather than an answer.

Who should take it

The course suits QA, QC and analytical staff who plan and interpret testing, regulatory affairs and CMC teams who report results and file changes, development and manufacturing scientists for active substances and finished products, and supplier quality staff who audit sources. Managers who sign off risk assessments or fund mitigation will find the decision rules and inspection expectations set out in a way they can act on. No prior nitrosamine training is assumed, but a working knowledge of GMP helps. Sites that supply both regions, or that rely on outside suppliers for their active substance, will gain most, because those are the places where gaps in a file most often appear.

What you can do afterwards

Learners finish able to review a synthetic route and a finished product for nitrosamine risk, ask suppliers the right questions and verify the answers, and convert an acceptable intake into a concentration limit for each market using the maximum daily dose. They can choose batches and a method sensitivity that fit the decision the results must support, place results in FDA's decision bands, and plan controls on the root cause rather than on the number alone. They also leave with a checklist they can use to find the gaps in their own file and keep it current as FDA and EMA update their expectations.