EMA's nitrosamine Q&A for MAHs: what PV and quality teams should check now

What happened

On 5 November 2026 the EMA published a questions-and-answers document for marketing authorisation holders and applicants on the CHMP opinion in the nitrosamine impurities procedure, reference EMEA-H-A5(3)-1490. The file name suggests it is a revised version of an existing Q&A, but the record we have does not say what has changed, so we cannot tell you which answers are new or amended.

That limit matters. Until teams have read the document against their current position, any claim about new expectations on timelines, testing or reporting would be speculation. This article therefore covers what the publication is, where it sits in the regulatory framework, and how PV and quality functions should approach it.

Why an Article 5(3) opinion matters

Article 5(3) of Regulation (EC) No 726/2004 allows the CHMP to give a scientific opinion on any matter relating to the evaluation of medicines, usually at the request of the European Commission or the EMA's Executive Director. It is not a referral that ends in a decision on a specific product's marketing authorisation. Opinions of this kind do, however, set the scientific reference point that national authorities and industry are expected to follow.

A Q&A attached to such an opinion is the practical layer. It is where regulators say how the opinion should be applied, and it is often the document inspectors and assessors have in mind when they question a company's approach. For MAHs, a Q&A is not legally binding in the way legislation is, but treating it as optional reading would be a mistake.

The PV angle on an impurity issue

Nitrosamines are a quality problem first. Control strategies, analytical testing and supplier oversight sit mainly with quality and CMC teams. The pharmacovigilance interface is real, though. QPPVs are accountable for the overall safety profile and for ensuring that safety-relevant information reaches the right people. When an impurity issue leads to batch actions, communications to healthcare professionals or benefit-risk questions, the PV system has to take part.

This week's other records show how often that interface is used. In Italy, AIFA published a DHPC on Respreeza after CSL Behring reported stopper defects in certain batches that could prevent administration or allow microbial contamination. In Greece, the EOF reports that PRAC is examining batch-specific allergic reactions with normal human immunoglobulin medicines. The records do not link that review to a cause, so it would be wrong to infer one. Both items show that batch-level and quality-related information increasingly appears in safety communications, and PV teams need a route to receive and act on it.

Who is affected and what to check

The Q&A is addressed to both MAHs and applicants, so it reaches holders of existing authorisations as well as companies with dossiers under assessment. In practice the main readers will be regulatory CMC, quality assurance and QPPV offices. Where the QPPV is not the document owner, they should still know what the company's position is and who owns it.

Three checks are sensible. First, compare the Q&A with the company's current nitrosamine risk documentation and any commitments made to authorities. Second, confirm that internal procedures cover how a quality finding, such as a test result above a limit, is escalated to PV and assessed for any safety consequence. Third, check that the contract and quality agreements with partners, contract manufacturers and licensees assign responsibility for receiving and passing on such information.

The wider safety picture shows why these links matter. MHRA's interim advice on Duvyzat (givinostat) after international reports of deaths in DMD patients, with more frequent ECG and electrolyte checks proposed and no UK deaths reported, is a clinical signal case. The Respreeza and immunoglobulin items are quality and batch cases. Different triggers, but each tests how quickly a company can move information between functions and across jurisdictions.

What to watch

The first open question is scope: which parts of the Q&A are new or revised, and whether they change MAH obligations or only clarify them. The record does not tell us. The second is how national competent authorities apply the document in inspections and variation assessments. The third is whether any impurity findings feed into PRAC or CHMP discussions beyond this Q&A.

Routine PV outputs continue alongside this. The EMA also published PSUSA outcomes this week for diethylamine-salicylate/escin and ethinylestradiol/gestodene, both with a regulatory outcome of maintenance. They are a reminder that most periodic safety assessments end without a change to authorisations, while quality-driven issues like nitrosamines can still require action across large product portfolios.