What is CAPA (corrective and preventive action) in pharma?

1What CAPA means.

ICH Q10, the pharmaceutical quality system guideline of June 2008, makes CAPA one of four elements of the quality system, beside process performance and product quality monitoring, change management and management review.¹ It defines the two halves in the words of ISO 9000:2005: corrective action is “action to eliminate the cause of a detected non-conformity or other undesirable situation”, and preventive action is “action to eliminate the cause of a potential non-conformity”. In short, “corrective action is taken to prevent recurrence whereas preventive action is taken to prevent occurrence.”¹

FDA’s 2006 guidance on quality systems treats CAPA as three concepts, adding the immediate fix: “remedial corrections of an identified problem”, root cause analysis with corrective action, and preventive action “to avert recurrence of a similar potential problem”.²

The definitions are from the guidance’s glossary.² FDA’s device training gives a plain example: fixing a misspelled word on a slide is a correction, and adding a spell-check to the way slides are prepared is a corrective action.³

2Where CAPA sits in the rules.

In the US, Part 211 does not use the words “corrective action” or “preventive action”. FDA ties corrective action to the discrepancy investigation requirements of 21 CFR 211.22(a) and 211.192, and lists no CGMP regulation for preventive action.²⁴ Section 211.192 requires any unexplained discrepancy or specification failure to be “thoroughly investigated, whether or not the batch has already been distributed”, extended to other batches and products that may be associated, with a written record that includes “the conclusions and followup”.⁵

In the EU, Chapter 1 of the GMP guidelines, revised to align with ICH Q10 and in operation since 31 January 2013, is explicit. Significant deviations are “fully recorded, investigated with the objective of determining the root cause and appropriate corrective and preventive action implemented”, and appropriate CAPAs “should be identified and taken in response to investigations”, with their effectiveness “monitored and assessed”.⁶ The product quality review should include a review of significant deviations and “the effectiveness of resultant corrective and preventive actions taken”.⁶

3Where CAPAs come from.

ICH Q10 expects a CAPA system for actions resulting from the investigation of “complaints, product rejections, non-conformances, recalls, deviations, audits, regulatory inspections and findings, and trends from process performance and product quality monitoring”.¹ FDA’s list of sources for corrective action adds returns, data and risk assessments, and management review decisions.²

Preventive actions come from looking ahead. FDA gives succession planning, training, capturing institutional knowledge and planning for changes as examples, and says problems can be anticipated “by reviewing data and analyzing risks” and by keeping up with scientific and regulatory change.² EU GMP asks for monitoring results to be used “with a view to taking preventive action to avoid potential deviations occurring in the future”.⁶

4How a CAPA runs.

FDA describes the procedure a quality system needs for corrective action in five parts.²

FDA calls it “essential to document corrective actions taken”, which CGMP also requires under 211.192.² ICH Q10 asks for “a structured approach to the investigation process” aimed at the root cause, with effort, formality and documentation “commensurate with the level of risk, in line with ICH Q9”.¹ EU GMP adds two points investigators often meet. Where the true root cause cannot be found, address the most likely one. Where human error is blamed, justify it after making sure “process, procedural or system-based errors or problems have not been overlooked”.⁶

5Checking that it worked.

Implementing an action is not the end. ICH Q10 says that in commercial manufacturing “CAPA should be used and the effectiveness of the actions should be evaluated”, and that CAPA should continue after a product is discontinued, considering product still on the market.¹ Management’s periodic review of the quality system should include performance indicators for the complaint, deviation, CAPA and change management processes.¹ For preventive actions, FDA says the system “should be monitored for the effectiveness of the action”.² ICH Q10’s aim for the whole system is that “CAPA methodology should result in product and process improvements and enhanced product and process understanding.”¹

6How it runs in Seal.

In Seal, the CAPA blueprint keeps the source deviation, investigation, actions, controlled change and follow-up evidence in one record, and the corrective action can be a controlled change to the workflow itself rather than only a revised document and a training task. The effectiveness review keeps its baseline, population, exposure and follow-up window, and closure can be configured to require the approved review. Seal’s quality management system covers deviations, CAPA, change control, documents, training, audits, suppliers, complaints and risk.

Neil, Seal’s AI agent, can compare a CAPA’s event rates before and after the action against a defined population and exposure measure. The CAPA owner assesses effectiveness and QA approves the conclusion.