Tag: ICH E6 (R2)

Let’s Stop Confusing Everyone With CAPA!

I am really not a fan of the term “CAPA”. I think people’s eyes glaze over at the mention of it. It is seen as an administrative burden that the Quality Department and Regulators foist onto the people actually trying to do the real work. And I think it’s a mis-named term. CAPA stands for Corrective Action, Preventive Action. When there is a serious issue arising in a clinical trial, a CAPA is raised. This is meant to get beyond the immediate fire-fighting of the situation and to get to root cause so that corrective and/or preventive actions can be put in place. Sounds sensible. But what about when I ask you what the difference is between a corrective and a preventive action?

ISO9001:2008 defines them as:

Corrective Actions – “The organization shall take action to eliminate the causes of nonconformities in order to prevent recurrence.”

Preventive Actions – “The organization shall determine action to eliminate the causes of potential nonconformities in order to prevent their occurrence.”

Not very easy to get your head around in part because of the use of the word ‘prevent’ in both definitions. And if a Preventive Action is designed to prevent occurrence then that means the nonconformity (error) cannot have already occurred. And yet a CAPA is raised when a nonconformity (error) has occurred. So the PA part of CAPA seems wrong to me. The different definitions of Corrective and Preventive have caused no end of confusion as organisations implemented ISO9001. The good news is that in ISO9001:2015, there is a significant update in this area. When a significant issue (non-conformity) occurs you are expected to implement those immediate actions to contain the issue (termed Corrections) and also Corrective Actions to try to prevent recurrence. But the Preventive Actions are not associated with the issue. They now fit into an overall risk approach. By assessing risks in processes up-front and then continuously through their life-cycle, you are expected to develop ways to reduce the risk. These are the Preventive Actions or in risk language, the Mitigations.

Sound familiar? In clinical trials of course, we have the ICH addendum (ICH E6 R2) bringing in significant language on risk which brings it more in line with the revised ISO9001:2015 standard and is a welcome change. What is odd is that the addendum includes the following in 5.20.1:

If noncompliance that significantly affects or has the potential to significantly affect human subject protection or reliability of trial results is discovered, the sponsor should perform a root cause analysis and implement appropriate corrective and preventive actions.

This, unfortunately, mentions preventive actions next to corrective ones without any explanation of the difference and no link to the approach to risk in section 5.0. So it seems the confusion will remain in our area of work. And that confusion is compounded by our use of the CAPA terminology.

I would vote to get rid of the CAPA term all together and talk about CAR (Corrective Action Requests) and Risk. Maybe along with that, we could rehabilitate the whole approach. Done well with good root cause analysis and corrective actions, CARs are an important part of a learning organization. They should not be seen as some tedious administration that the Quality Department is requesting.

What do you think? Perhaps it’s all clear to you and you think CAPA is a great term?

In my next post I want to go back into the root cause analysis (RCA) process itself – whether DIGR® or another method. I’ll talk more about the corrosive effect of blame on RCA and how to overcome it.

 

Text: © 2017 Dorricott MPI Ltd. All rights reserved.

DIGR® is a registered trademark of Dorricott MPI Ltd.

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Root cause analysis can help you sleep at night

Who cares about root cause analysis (RCA)? Of course, we all do now it’s in the revised GCP, the ICH E6 (R2) Addendum*. But does it really matter? It’s easiest to think through from the perspective of an example. Consider a hypothetical situation where you are the Clinical Trial Lead on a vaccine study. Information is emerging that a number of the injections of trial vaccine have actually been administered after the expiry date of the vials. This has happened at several sites. Some example actions you might take immediately are – review medical condition of the subjects affected, review stability data to try to estimate the risk, ask CRAs to check expiry dates on all vaccine at sites on their next visit, remind all sites of the need to check the expiry date prior to administering the vaccine. These and many other actions are ones your team could quickly generate and implement and they will likely contain the issue for now. It took no root cause analysis to generate these actions. Could you sleep being confident in the knowledge that the problem won’t recur?

Without RCA, you don’t really know why the problem occurred and so you can’t fix it at the source. All you can do is put in additional checks and as these are implemented reactively, they may not be properly thought through and people may be poorly trained (or not trained at all) on the additional checks. We also know that while checks are valuable in a process they are not 100% effective when carried out by people. In this example we can be sure that the pharmacist dispensing and the nurse administering the vaccine have been trained to check the expiry date and yet we still have cases where expired vaccine has been administered. Do we really think that reminding the pharmacist and nurse is going to be enough to fix the problem forever? In a future blog, I will describe a powerful technique for RCA but for now, imagine you had managed to carry out a root cause analysis on this situation.

What you might discover in carrying out a RCA is that there is no defined process for informing sites of expired vaccine and requiring them to quarantine it. Or perhaps that the expiry date is written in American date format but being read in European format (3/8/16 being 8-Mar-2016 or 3-Aug-2016). Whatever the actual root cause, by finding what it is (or they are) you can start to consider options to try to stop recurrence. And with additional checks you could look for early signals in case these actions are not effective. By taking these actions, would you be more likely to sleep at night?

Think you know about RCA? In my next blog I will reveal why the Five Whys method we’re always told to use is not good enough for a complex situation such as this. And later, I will provide a description of a powerful technique for RCA that seems to be seldom used. If you want to hear more, please subscribe to my blog on the left of the screen. All comments welcomed!

And did you notice that I haven’t mentioned CAPA once (until now!)

* Section 5.20.1 Addendum: “If noncompliance that significantly affects or has the potential to significantly affect human subject protection or reliability of trial results is discovered, the sponsor should perform a root cause analysis and implement appropriate corrective and preventive actions.” [my emphasis]