High frequency of CAPA related observations in Warning Letters.

Posted on July 18, 2013

Globiox proactively monitors FDA inspection trends by reviewing and analyzing the contents of the Warning Letters. A current trend we detected is the high frequency of observations related to Corrective and Preventive Actions (CAPA) in Warning Letters. Out of 43 Warning Letters issued to Medical Device companies (since March 22, 2013), 29 have contained observations relating to Corrective and Preventive Actions (CAPA) deficiencies 21 CFR 820.100. Of these 29 Warning Letters:

1) Six companies simply had no CAPA procedures in place.
2) Five companies had deficiencies in their documentation, such as missing records.
3) Nine observations detailed issues related to Root Cause Investigations.
4) Nine other observations indicated a lack of effectiveness verification for various solutions implemented to close CAPAs.

In looking at the data, the causal factors can be classified into four issues.

The first issue involves the lack of a documented CAPA process.  A majority of the companies cited did not have documented CAPA procedures.  Some companies had various procedures dealing with some aspects of the CAPA process, but did not have a formal, centralized process covering all regulatory requirements. 

The second issue involves CAPA documentation.  Several of the companies cited did not have an effective CAPA process.  An effective CAPA process requires clear and comprehensive written SOPs and records detailing the opening, tracking, closure, and effectiveness check of CAPAs.

The third issue involves the lack of a meaningful root cause investigation.  Many of the companies cited lacked a detailed formal investigation process ensuring a methodical determination of a true root cause.  The adoption of Six Sigma methodology can increase the effectiveness of the root cause investigation. Tools such as fishbone diagrams, the “5 whys” method, Failure Mode Effects Analysis, and rigorous checklists (yes/no questions) can be incorporated into investigation process.  

The final issue category we observed was a lack of effectiveness verification for CAPAs. 21 CFR 820.100(a)(4) states that CAPA procedures shall include requirements for “verifying or validating the corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device.”   Effectiveness verification is the final step to closing out a CAPA. This includes verifying that the corrective and preventative actions fixed any outstanding problems and will prevent the problem’s reoccurrence.  Six Sigma methodologies can be very useful to incorporate into the verification process to assure an effective verification.  CAPA program monitoring will indicate if problems re-occur due to the same root cause. Monitoring the volume of CAPAs over time can be useful because variations from normal trends can indicate organizational issue that might not otherwise be readily apparent. Monitoring the length of time it takes to close CAPAs is important as well, because it allows one to see if issues are being solved in a timely manner.  If you would like to discuss your CAPAs then contact us.


Bill Schroeder  |  August 01, 2013

"This trend, as well as the common comment "Quality Unit failed to....", can be traced back to FDA guidance on Quality System maturity put out in September of 2006. The FDA, and subsequently the ICH, have published that they are looking more intently at the health and maturity of the overall quality system to police itself. The CAPA program is a good indicator of the systems ability to monitor how the company is managing its overall quality of the products. That is the most likely reason that we see more warnings on these systems."

Globiox  |  August 02, 2013

"Thank you for your comment Bill. We agree that the FDA is looking more at maturity of Quality Systems now.
There are some interesting statistics recently released by the FDA. In a 2013 survey of medical device manufacturers, most of them were using traditional audit data (91% Internal Audit Data and 81 % 3rd party audit data) as sources of Quality Data to be examined in their CAPA system. But far fewer companies were using process data sources (72% process control data, 61% equipment data, 76% inspection/final test data).
This may indicate that CAPA systems are not as mature as we (and the FDA) would hope they are."

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