At SCOPE Europe in Barcelona earlier this month, I took the opportunity to talk with people about the proposed changes to section 5.0 of ICH E6 on Quality Management. People mostly seemed as confused as I was with some of the proposed changes. It’s great we get an opportunity to review and comment on the proposal prior to it being made final. But it is guesswork trying to determine why some of the changes have been proposed.
ICH E6 R2 was adopted in 2016 and section 5.0 was one of the major changes to GCP in twenty years. Since then, organizations have been working on their adoption with much success. Predefined Quality Tolerance Limits (QTLs) is one area that has received much discussion in industry and has been much written about. And I have listened to and personally led many discussions on the challenges of implementation (including through the long-running Cyntegrity mindsON RBQM series of workshops which is nearing episode twenty this year!) So much time and effort has gone into implementing section 5.0 and much of it remains intact in the proposed revision to E6 R3. And there are some sensible changes being proposed.
But there are also some proposed changes that appear minor but might have quite an impact. I wonder if the risk of making the change is actually worth the potential benefit that is hoped for. An example of such a proposed change is the removal of the words “against existing risk controls” from section 5.0.3 – “The sponsor should evaluate the identified risks, against existing risk controls […]” We don’t know why these four words are proposed to be dropped in the revised guidance. But I believe dropping them could cause confusion. After all, if you don’t consider existing risk controls when evaluating a risk then that risk will likely be evaluated as being very high. For example, there may be an identified risk such as “If there are too many inevaluable lab samples then it may not be possible to draw a statistically valid conclusion on the primary endpoint.” Collecting and analysis of lab samples is a normal activity in clinical trials and there are lots of existing risk controls such as provision of dedicated lab kits, clear instructions, training, qualified personnel, specialised couriers, central labs etc. If that risk is evaluated assuming none of the existing risk controls are in place, then I am sure it will come out as a high risk that should be controlled further. But maybe the existing risk controls are enough to bring the risk to an acceptable level without further risk controls. And there may be other risks that are more important to spend time and resource controlling.
We don’t know why the removal of these four words has been proposed and there may be very sound reasons for their removal. As someone experienced in helping organizations implement RBQM and an educator and trainer, however, it is not clear to me. And I worry that a seemingly simple change like this may actually cause more industry confusion. It may take time and resource away from the work of proper risk management to process, system, and SOP updates. It may delay still further some of the laggards in implementing Risk-Based Quality Management (RBQM). Delaying implementation is bad for everyone, but particularly patients. They can end up on trials where risks are higher than they need to be and patients may also not get access to new drugs as quickly because trials fail operationally (as their risks have not been properly controlled).
So my question is, is the risk of modifying RBQM in GCP worth it?
The deadline for comments on the draft of ICH E6 R3 has now passed. The guidance is currently planned for adoption in October 2024. I’ll be presenting my thoughts on the proposed changes at SCOPE in Florida in February.
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Picture: Neil Watkins