Handling of Deviations and CAPA criticised by Inspectorates

Deviations and CAPA remain hot topics in inspections. The inspectorates' summaries of their observations show that things do not always work as desired. Recently, the British authority MHRA (Medicines and Healthcare Products Regulatory Agency) published its Top Ten Deficiency Categories. The report "Deficiency Data Review April 2011 to March 2012" covers the period from April 2011 to March 2012 and summarises the observations of 303 inspections.

The most common deficiencies during the time frame considered are listed below regardless of the sector involved:
1. Investigation of Anomalies
2. Quality Management / Change Control
3. CAPA
4. Complaints and Product Recall
5. Quality Management
6. Supplier and Contractor Audit
7. Potential for Contamination
8. Documentation / Technical Agreements
9. Documentation - Manufacturing
10. Process Validation

As in the previous year, the investigation of anomalies is again at the top of the list. Observations concerning CAPA issues already follow on the third position.

What are the reasons for this? The MHRA published a set of 16 frequently asked questions concerning this topic (FAQs) concerning Quality Risk Management (QRM) already in 2010. The questions and the relevant answers give a good overview and useful tips on how EU inspectorates inspect QRM elements in relation to the ICH Guidelines Q9 and Q10 and how they intend to enforce them. The British authority has emphasised particularly that all inspectorates will include QRM processes in the future, since they are required in chapter 1 of the EU-GMP Guide (Part 1). This includes the handling of complaints, the management of deviations and CAPA.

"Production Record Review" - is the point most often cited in FDA Warning Letters for five years now. 

In the past fical year (FY 2011, from October 2010 until September 2011) the FDA has issued a total of 39 Warning Letters to domestic and foreign pharmaceutical companies. This is nearly the same number as in the FY 2010 when 41 companies received a Warning Letter. It is interesting to note that the GMP deficiency which has been complained about most often for the fifth consecutive year is a violation of the requirements of 21 CFR 211.192 "Production Record Review".

Taking a closer view it is obvious that most observations are reducible to "Failures in deviation management" and to a lack of CAPA. In most cases the companies have observed and recorded deviations (in the production record) but this resulted neither in (verifiable) investigations nor in other consequences.

The following are some examples taken from the FY 2010: 

• "Your firm failed to perform an investigation or determine the root cause…" 
• "No corrective or preventive action was documented" 
• "We are unable to evaluate these corrective actions because you failed to provide supporting documentation" 
• "You failed to conduct adequate investigations that result in your implementation of corrective actions to prevent recurrence of the problems and evaluate other potentially affected lots" 
• "Although a deviation investigation was conducted, the investigation was not thorough (e.g., identification of other affected lots, root cause determination, and corrective and preventive actions)"

Actual developments such as the Quality System Guide published by the FDA, ICH Q10 and these inspection results clearly underline the increasing importance of CAPA.

Wolfgang Schmitt
CONCEPT HEIDELBERG (a service provider entrusted by the ECA Foundation)