Current risk-based framework for nitrosamine assessment, including NDSRIs, formation risk, confirmatory testing, acceptable intake and control strategy.
Nitrosamine control is a lifecycle process that connects formation-risk assessment, analytical confirmation, toxicological limit setting and mitigation. Current frameworks distinguish small-molecule nitrosamines from nitrosamine drug substance-related impurities (NDSRIs).
Formation risk
Risk can arise from nitrosating conditions, susceptible amines, nitrite sources, API degradation, excipients and manufacturing or storage conditions.
Confirmatory testing
When risk is identified, appropriately sensitive analytical testing can determine whether a nitrosamine is actually present and at what level.
Acceptable intake
Limits may be based on agency-established values, CPCA, compound-specific data or read-across, depending on the available evidence.
Control strategy
Process, formulation, supplier and analytical controls should address the identified root cause and maintain the impurity below the applicable limit.
Frequently asked questions
What is an NDSRI?
A nitrosamine impurity structurally related to the drug substance or API fragment.
Does every theoretical nitrosamine require confirmatory testing?
The need depends on the documented risk assessment and applicable regulatory expectations.
Are acceptable-intake tables static?
No. Agencies update them as new evidence becomes available.
Should current agency tables be checked before setting a limit?
Yes.