EMA PQS effectiveness pilot: moving from documented procedures to demonstrated results

Many pharmaceutical quality systems can show a mature document architecture: approved procedures, trained users, change-control forms, risk-assessment templates and governance forums. The harder leadership question is whether those arrangements consistently produce sound, timely and sustainable decisions in practice.

EMA’s Pharmaceutical Quality System (PQS) effectiveness pilot brings that question into sharper inspection focus. The pilot, run by the GMP/GDP Inspectors Working Group, assesses how a manufacturing site can demonstrate the effectiveness of its PQS for risk-based change management. It also evaluates whether the EEA GMP certificate could serve as the principal evidence of that effectiveness.

This is not an inspection of whether a site owns a procedure. It is an examination of how the change-management system operates through real changes, quality risk management (QRM), product quality reviews (PQRs) and the wider PQS.

The practical test is simple: can the site show, using a coherent body of evidence, that its change-management process identifies risk, drives appropriate action, detects unintended consequences and supports a sustained state of control?

What EMA is piloting

EEA GMP inspectors will pilot the use of the PIC/S guidance, How to Evaluate and Demonstrate the Effectiveness of the Pharmaceutical Quality System with regard to Risk-based Change Management, during selected GMP inspections between 2026 and 2027. EMA states that the PIC/S paper is supportive guidance; inspections remain conducted against the requirements of the EU Guide to GMP, and any deficiencies observed will be recorded against EU GMP requirements in the usual way.

The pilot is connected to the revised EU variations framework, applicable from January 2026. EMA identifies robust PQS effectiveness as a key requirement for using the additional regulatory tools introduced through that framework, including the Product Lifecycle Management document.

For participating sites, the inspection focus is specifically change control and change management. EMA lists the following areas as in scope:

• the site’s overall approach to change management and its use of QRM;
• how change management and related QRM activities are documented within the PQS;
• change-control procedures and forms;
• specific regulatory-impacting and non-regulatory-impacting change controls;
• risk assessments and other QRM activity relating to changes;
• how changes are reviewed in PQRs; and
• the extent to which the site’s approach reflects the PIC/S paper.

The pilot will also assess whether, and how, effectiveness relating to risk-based change management could be recorded on a GMP certificate or in a GMP inspection report.

What this does—and does not—change

GuideGxP recommendation: avoid presenting the pilot internally as a new standalone GMP obligation. Instead, use it as a disciplined challenge to assess whether the site can demonstrate the effectiveness of the controls it already relies upon.

Why recurring deviations and CAPA matter

A site may close a change control correctly on paper while still failing to demonstrate effectiveness. The most persuasive evidence is rarely a single completed form. It is the traceable story across the lifecycle of a change: the reason for change, risk-based decision-making, implementation, verification, monitoring and learning.

Recurring deviations are especially informative. If the same failure mode returns after a process, equipment, analytical, supplier or procedural change, leadership should be able to explain whether the original change assessment identified the risk, whether the implementation was as intended, and whether the effectiveness checks were sufficiently sensitive and long enough.

CAPA data should be read in the same way. A closed CAPA is an administrative status; it is not, by itself, proof that the underlying system has improved. Where a CAPA changes a GMP process, the associated change control, risk assessment, implementation evidence and post-implementation review should tell one consistent story. Contradictions between those records are a warning that the PQS may be documenting activity without reliably controlling outcomes.

GuideGxP recommendation: select a small number of material completed changes and reconstruct their end-to-end evidence. Include examples with different risk profiles, including a regulatory-impacting change where available. Test whether an independent reviewer can understand the rationale, risk acceptance, approvals, implementation, outcome and any subsequent learning without relying on verbal explanation.

Make management review an effectiveness forum

Management review is where site leadership can determine whether local signals reveal a broader PQS issue. For change management, this means going beyond the number of changes opened, approved or overdue.

Useful effectiveness questions include:

• Are particular types of change repeatedly associated with deviations, complaints, OOS/OOT trends, validation concerns or supply disruption?
• Do post-implementation checks show that risk controls worked as predicted?
• Are changes being implemented before prerequisite actions, training or qualification are demonstrably complete?
• Are recurring events revealing inadequate risk assessment, weak technical transfer, ineffective CAPA or insufficient monitoring after implementation?
• Does PQR review identify product- or process-specific effects that should trigger reassessment of prior changes?
• Are quality decisions escalated quickly enough when effectiveness evidence is weak or contradictory?

These are operational recommendations, not additional pilot requirements. Their value is that they turn management review into a mechanism for assessing performance and directing action, rather than merely receiving a summary of process compliance.

Preparing a defensible evidence trail

EMA notes that a voluntary inspection without a planned routine inspection may be relatively short—half a day or one day—and may involve one GMP inspector. That creates a premium on clarity. A site should be able to retrieve material rapidly, explain its governance consistently and connect system-level data to individual changes.

1. Establish the system narrative

Define how change management operates at the site: governance, QRM integration, decision rights, categorisation, regulatory assessment, implementation controls, closure criteria and ongoing review. Ensure the narrative matches approved procedures and the way users actually work.

2. Curate representative change cases

Prepare traceable case files rather than a large undifferentiated document dump. Each file should link the change record with risk assessments, technical and quality approvals, implementation records, training or qualification evidence where relevant, deviations, CAPAs, PQR references and effectiveness review.

3. Test the links between PQS elements

Inspectors may look at specific change controls as well as the overall approach. Check that records cross-reference accurately and that the same risk rationale does not appear differently in a change record, deviation investigation and CAPA. Address unexplained inconsistency before it becomes an inspection discussion.

4. Use data to challenge effectiveness

Trend relevant outcomes before and after selected changes. The appropriate measures will vary by process and product, but the site should be able to explain why a measure was selected, what result was expected, how long performance was monitored and what action would follow if the expected result was not achieved.

5. Rehearse leadership oversight

Site leaders, QA, operational owners and the QP should be aligned on what the data mean. The objective is not rehearsed wording; it is a common, evidence-based understanding of when the system performed well, where it was challenged and how management responded.

Participation and immediate decisions

Manufacturers may nominate EEA sites until 31 December 2026. Marketing authorisation holders may nominate EEA sites where a planned variation submission concerning a Product Lifecycle Management document will rely on the manufacturer’s PQS. EEA supervisory authorities may also nominate sites based on planned inspections. EMA states that inspections may be carried out up to 1 March 2027.

The pilot is expected to cover a range of manufacturing sites, including sterile and non-sterile finished-product sites and biological API sites. EMA also identifies circumstances and site types that are not eligible, including ATMP sites, medicinal-gas sites, radiopharmaceutical manufacturers, sites under Compliance Management in the EEA, and sites with Statements of Non-compliance or restricted GMP certificates issued by an EEA authority.

GuideGxP recommendation: participation should be a conscious leadership decision, not simply an inspection opportunity. Consider whether the site has a stable change-management operating model, accessible electronic and paper records, mature cross-functional governance and the capacity to convert inspection findings into durable improvements.

Conclusion

The EMA pilot creates a useful distinction between having a PQS and demonstrating that it works. For QA and site leadership, the most important preparation is not the production of another procedure or presentation. It is the ability to show that risk-based change management produces reliable decisions, is reviewed through PQR and management governance, and is challenged when deviations or CAPA outcomes indicate that control has not been sustained.

A documented process is necessary. Demonstrated effectiveness is the stronger standard.

Official source

• European Medicines Agency: Pharmaceutical quality system (PQS) effectiveness pilot project