All manufacturing sites have a CAPA system, usually a mechanism to deal with things that have gone wrong. Despite the fact that a lot of focus has been given to CAPA in recent years, there is a great deal of misunderstanding and a clear lack of clarity on what CAPA actually is. This may explain why many organisations feel that they are still in “fire-fighting” mode – always dealing with yesterday’s problems rather than preventing future issues from occurring.
Lack of regulatory guidance
“Corrective Action and Preventive Action” is mentioned a few times in EU GMP, most notably in Chapter 1 where it says “Corrective Actions and/or Preventative Actions (CAPAs) should be identified and taken in response to investigations” (EU GMP 1.4 xiv). It is also mentioned in a similar way in Chapter 8. But, there is no section in any part of the 9 chapters of EU GMP covering CAPAs and CAPA systems. Both the FDA’s “Guidance for Industry: Quality Systems Approach to Pharmaceutical CGMP Regulations” and ICH Q10 “Pharmaceutical Quality System” talk about CAPA and CAPA systems, and here the main problem starts to be highlighted. This problem comes from combining the two (having CAPA) rather than CA and PA, which are in-fact two distinct processes.
The FDA’s “Guidance for Industry: Quality Systems Approach to Pharmaceutical CGMP Regulations” talks about CAPA as follows (reference III D):
CAPA is a well-known CGMP regulatory concept that focuses on investigating, understanding, and correcting discrepancies while attempting to prevent their recurrence. Quality system models discuss CAPA as three separate concepts, all of which are used in this guidance.
- Remedial corrections of an identified problem
- Root cause analysis with corrective action to help understand the cause of the deviation and potentially prevent recurrence of a similar problem
- Preventive action to avert recurrence of a similar potential problem
And this is very much peoples’ understanding of CAPA. But dig deeper and in the same document you’ll find contradiction in the glossary with regard to CA and PA.
- Corrective Action – Action taken to eliminate the causes of an existing discrepancy or other undesirable situation to prevent recurrence.
- Preventive Action – Action taken to eliminate the cause of a potential discrepancy or other undesirable situation to prevent such an occurrence.
These two definitions are closer to the ISO 9000 series of definitions for CA and PA, which does not join the two up. In other words Corrective Action is re-active and Preventive Action is pro-active. It is not possible to do Preventive Action once a problem has occurred, PA takes place before a problem has occurred in the first place.
We can learn a lot from ISO 9000 in how it defines the terms Correction, Corrective Action and Preventive Action. In ISO 9000 theses are defined as below, with an analogy provided by the author.
Correction (3.12.3) – action to eliminate a detected nonconformity.
- Analogy – we retrain the operator, rework the batch, recalibrate the gauge.
Corrective Action (3.12.2) – action to eliminate the cause of a nonconformity and to prevent recurrence.
- Analogy – we perform a root-cause analysis to find out why the problem occurred and put in mechanisms to prevent it from ever happening again.
Preventive Action (3.12.1) – action to eliminate the cause of a potential nonconformity or other potential undesirable situation.
- Analogy – before we started to run the process we did a detailed risk-assessment of where anything could possibly go wrong and put in systems to prevent these from occurring in the first place.
In many cases where I have seen CAPA systems in pharmaceutical operations the actions that they term Corrective Actions are actually “Corrections”. The actions that they term Preventive Actions are actually “Corrective Actions” and Preventive Action (doing something before a problem occurs) does not actually feature in the generally re-active CAPA system.
The lack of getting to the root-cause of a problem (doing “Correction” rather than “Corrective Action”) along with no real formal system for Preventive Action may well explain why many organisations are fighting fires and dealing with problems that keep coming back.
This may well not be the case in your own organisation, but I strongly suggest you just take a brief look at what your own internal definitions and general understanding of CA and PA actually are. This may well be a couple of minutes well spent.
Please feel free to make a comment on what you think of this article. It has already raised great interest and debate.
THIS ARTICLE WAS FIRST PUBLISHED IN 2012 AND WAS REVISED AND UPDATED IN OCTOBER 2022.
Annex 1 has finally arrived, 25th Aug 2022 saw the publication of Annex 1. Normally, updates to GMP chapters and Annexes have a 6-month lead time for implementation. In the case of the new Annex 1, the lead time is 12 months, except for clause 8.123 relating to lyophilization which has 24 months lead time.
Annex 1 was first issued in 1971 as the only annex in the first ever UK guide to Good Manufacturing Practice. Since then, there have been several updates but not full revisions. In 2012 there was a proposal to revise Annex 1 with a re-proposal in 2014 by the UK’s MHRA. At the time, a full rewrite was considered unlikely and instead the intention was to provide a document that would confirm regulatory expectation and as such, not place any new requirements or costs on the pharmaceutical industry.
While this principle, is still upheld, it was clear from the first draft for public comment of December 2017, that a rewrite was being undertaken. The first draft created around 6200 comments coming from regulatory organizations, such as the pharmaceutical cooperation scheme, regulatory bodies outside of the EU, support organizations such as the Parenteral Drug Association, the Parenteral and Healthcare Sciences Society, the Pharmaceutical Microbiology Interest group as well as representatives from the manufacturers within the pharmaceutical industry to name just a few. Rarely do updates require a second public consultation but in the case of the annex 1 update a second draft was issued in March 2020 although this was a more targeted review in terms of the sections and clauses that comment was being sought for.
About the author
Andy started working in the Pharmaceutical industry in 1985 as a lab technician for Smith & Nephew. Following this he had a number of roles culminating when he took over as QA Microbiology Manager. In 2003 he moved into Pharmaceutical Training and then in 2007 he moved back into Microbiology when he took up the position of Microbiology Manager for Catalent Pharma Solutions. Since 2012 he has operated as a consultant specialising in Microbiology and Quality Systems.
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