RISK ASSESSMENTREFERENCE OUTLINE

Nitrosamine Impurity Risk Assessment

A structured nitrosamine risk assessment covering the three-step process — risk evaluation, confirmatory testing, and risk control — for API and drug-product sources of N-nitrosamine and nitrosamine drug-substance-related impurities (NDSRIs), with acceptable-intake comparison and a control strategy. Aligned to the EMA and FDA nitrosamine guidance and ICH M7(R2).

What a template is not

A template is a document baseline to adapt inside your own quality system. SPEQ does not approve, validate, or take responsibility for what you issue from it, and using one is not evidence of compliance.

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REGULATIONS MAPPED
EMA nitrosamine guidanceFDA nitrosamine guidanceICH M7(R2)
DOCUMENT TYPE
Risk Assessment
LAST UPDATED
August 2026
PURPOSE

The assessment that works through risk evaluation, confirmatory testing and risk control for a specific product, and records the conclusion in a form that can be reopened when new information arrives. The common failure is treating it as a one-off exercise: a supplier changes a route, a new NDSRI is described, and the file still reflects the original assumption. The acceptable intake applied is your determination and must carry its basis.

What's Inside

✓Source inventory across API route, excipients, packaging, water, recovered solvents, cross-contamination and degradation pathways
✓Risk evaluation per source, with the reasoning recorded so a low-risk conclusion can be challenged later
✓Acceptable-intake determination and its basis, stated per nitrosamine rather than assumed across the class
✓Confirmatory testing plan naming the method and its sensitivity relative to the acceptable intake
✓Results and comparison against the acceptable intake, including how a non-detect result was interpreted
✓Risk-control strategy — the specific change to route, supplier, specification or packaging that lowers the risk
✓Residual-risk conclusion with named review triggers, so a supplier or route change reopens the file

How to Use It

1Inventory every potential source across the product and its supply chain before scoring anything; an unlisted source cannot be evaluated
2Evaluate each source on record, and write the reasoning for low-risk conclusions — those are the ones challenged in review
3Establish the acceptable intake for each identified impurity with its basis; a limit carried over from another product is not a basis
4Test with a method whose limit of quantitation is meaningfully below the acceptable intake, or the result cannot support the conclusion
5Define controls that change the process or the supply chain, not controls that only increase testing of an unchanged risk
6Name the triggers that reopen this assessment — route change, new supplier, new formulation — and diarise the periodic review
DOCUMENT CONTENTS

The full section structure of this template — every section and sub-section, so you can use it as a baseline for your own site document.

—Document Control
› Document Information› Approval Signatures› Revision History› Distribution List
1Product and Scope
2Step 1 — Risk Evaluation and Source Inventory
3Step 2 — Acceptable Intake and Confirmatory Testing
4Step 3 — Risk Control and Conclusion
REGULATORY CONTEXT

The EMA and FDA nitrosamine guidances set the three-step expectation — risk evaluation of all potential sources, confirmatory testing where risk is identified, and risk control — and ICH M7(R2) supplies the mutagenic-impurity framework the acceptable-intake logic sits within. What they do not do is decide your product’s sources, your method sensitivity, or whether a residual risk is acceptable to market. Those are marketing-authorisation-holder determinations, and this assessment records them with their reasoning intact rather than as a bare conclusion.

MAPPED STANDARDS
EMA nitrosamine guidanceFDA nitrosamine guidanceICH M7(R2)
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