If you’re seeing the same deviations pop up (gowning fibers in the dryer room, unexplained assay drift after solvent changeover, or audit trails with gaps, for example), then it’s not necessarily a “people performance problem“ alone. Rather, it may suggest that depth in the root-cause analysis (RCA) within the investigation process may also be an issue. Currently, in Europe, regulators expectations are that your RCA will be: (1) risk-based; (2) data-credible; and (3) have Corrective and Preventative Actions (CAPAs) tied to tangible actions that change personnel behavior on the floor. It is a stepwise approach…
Follow ICH Q9(R1)
Following ICH Q9(R1), which became effective in Europe in July 2025, it is more appropriate to be framing risk as more extensive than just “operator error.” Use a structured blend—a straightforward fault tree to map failure paths, Failure Mode and Effects Analysis (FMEA) to prioritize harms, and a human-performance lens to tease out error-likely conditions (including confusing SOP steps, poor line of sight to critical parameters, inadequate training on-the-job, and fatigue). Anchor these results in Q9(R1)’s emphasis on uncertainty, subjectivity, and data quality, followed by illustrating how you reduced those uncertainties as you learned.
Make Your RCA Evidence Inspection-Ready
European inspectorates are leaning on hybrid and remote models, and they’re asking to see how conclusions were reached, not just the conclusion itself. Keep a clean chronology of events from signal to dataset to analysis to decision, with audit-trail reviews and raw dataset snapshots attached. This step aligns with the recent Medicines and Healthcare products Regulatory Agency (MHRA) commentary on international inspection transformation and the broader Pharmaceutical Inspection Co-operation Scheme (PIC/S) focus on data integrity.
Mind the Nitrosamines
In 2024, the European Medicines Agency (EMA) updated its Q&A again, tightening expectations for confirmatory testing, analytical methods, dossier triggers, and responsibilities when the API relies on a Certificate of Suitability (CEP). For API manufacturers, this means that RCAs around impurity-formation routes must integrate reaction-mechanism thinking (amines + nitrites + conditions), supplier changes, and cleaning interactions—and then lock in preventive barriers at the process and a lifecycle level. If your API supplier gets a GMP non-compliance statement in EudraGMDP, the European Directorate for the Quality of Medicines & HealthCare (EDQM) may suspend or withdraw CEPs, which, for a product manufacturer, should be factored in when considering supplier contingencies.
Close the Loop Where it Counts: Operational Behavior
Translate each true root cause into a control that’s observable on the line—parameter setups with engineered “pause points,” quality-related linked micro-work aids at the reactor, peer-verification checks on calculation steps, and targeted coaching for the few steps with the highest defect opportunity. Track leading performance indicators (first-time-right-weighed additions, intervention adherence, and audit-trail review timeliness) and show the trend flattening before you relax controls. European API groups like the Active Pharmaceutical Ingredients Committee (APIC) are doubling down on data-integrity practices—use their latest FAQs to sharpen your behaviors and checks. Finally, treat the RCA like a CAPA you’d be proud to defend—specific cause, interim actions (as needed), proportional fix, and verified effectiveness. Do that, and the same deviation won’t darken your doorstep twice.
If you or your firm need assistance with either recurring deviations or looking at your RCA plan, Lachman can help! Reach out to us at LCS@LachmanConsultants.com for a consultation.
