The handling and examination of nonconformances and deviations is becoming more and more important to the pharmaceutical industry, primarily for two reasons. Firstly, the ongoing modernisation of pharmaceutical quality management systems has made the industry recognise the value and benefit of "failure" detection and CAPA (Corrective and Preventive Action). Continuous process improvement tools have a long and successful history, especially in the automotive industry, and these are now being adopted and implemented in the pharmaceutical industry. Applied properly, nonconformances can be prevented and processes can be continuously improved.
Secondly, the regulatory requirements and expectations of government agencies worldwide have continued to increase in recent years. In November 2009, for example, the UK Medicines and Healthcare Products Regulatory Agency (MHRA) published a "Deficiency Data Review"1 for the period April 2008 to March 2009, in which it cited "anomalies" as their most frequent observation of regulatory deviations, with nonconformances and deviations in conjunction with CAPA being the third most common observation. This is similar to the findings of the recently published FDA Warning Letters Report from the European Compliance Academy (ECA).2 Here, the deficiencies in the "Production Record Review" (21 CFR 211.192) are among the most frequently reported GMP deviations. According to the report, more production record review deviations were observed in 2009 than in any other years and, on closer examination, most of the objections applied to the poor handling of deviations and incorrect CAPAs. In most cases, the companies did actually detect the deviations themselves, but did not properly examine them and did not define appropriate corrective and preventive actions. So what went wrong?
Industry's common failingsIt seems that one of the biggest challenges for companies is to complete investigations and actions in a timely manner. In many cases, incorrect assumptions are made that everything is an isolated incident. In other instances, problems are not corrected and everything is blamed on a single employee or a simple laboratory error, or the system fails to ensure that a problem does not extend to other lots, and the incident recurs. The ultimate criterion for adequate correction is to ensure that it doesn't happen again!
CAPA was adopted as a new quality management tool following the introduction of the ICH Q10 guideline. According to the ICH Q10 document, which was adopted by the FDA in April 2009 as an industry guideline, a pharmaceutical Quality Management System (QMS) consists of four central elements:
The guideline states that a pharmaceutical company should have a system in place to detect and evaluate nonconformances to take respective corrective and preventive actions. Among other things, the information regarding nonconformances can result from complaints, deviations, recalls, observations at audits and inspections, or from monitoring findings. The examinations within the system must have the objective of determining the actual root cause. As a result, the process and product should be better understood so that improvements can be derived from it.
The EU Commission has now published a suggestion for the revision of chapter 1 of the EU GMP Guide to incorporate the recommendations of ICH Q10. Now, specific requirements for a CAPA system shall be included. A comprehensive description can be found in section 1.8 items 7, 8 and 9, in conjunction with the requirements for quality risk management systems according to ICH Q9 (identical to annex 20 of the EU GMP Guide). Accordingly, the extent of the actions, technical complexity and documentation of the necessary CAPA actions have to be managed according to a risk assessment. In doing so, it will become more and more important to fulfil these requirements and expectations quickly and smoothly, whilst keeping an eye on the economical and operational situation.