New GCP guideline based on a ‘fit for purpose’ perspective

‘In my opinion, this revision has mainly advantages, because it is written from a pragmatic, less rigid perspective on conducting clinical trials,’ says Compliance Director Margreet Rienstra. The publication of R3 in January 2025 was quite a job for her and her colleagues, because according to European and Dutch rules, the new guideline had to be implemented within six months. ‘Our regular work of course continued, so this was an additional challenge,’ says Rienstra. ‘But thanks to the flexibility of our QA/compliance team and several other colleagues, it all went smoothly.’

‘The basic principles of GCP have, of course, remained unchanged: the safety of participants and the reliability of data, in that order of importance,’ says Rienstra. ‘The main intention of this rewrite is to modernise GCP and to replace the ‘one size fits all’ approach of earlier versions with the premise that the approach to clinical trials should be risk-based and ‘fit for purpose’, i.e. appropriate for this specific clinical trial. I think that’s an improvement, because what is critical for one trial may not be critical for another.’

An important first step for each study is therefore to define its ‘critical to quality factors’. Some of these factors stem from the nature of the compound and what is known about it. In addition, it is up to CHDR to determine which operational factors are critical to quality. Rienstra: ‘An example of this could be if we have to do something differently from our standard procedure, for example if we have to use a new device or deliver something in triplicate when we normally do so in duplicate. Then you know that there is a risk of errors occurring. Risk management means recognising these kinds of factors and mitigating risks before they occur.’

As part of the implementation of R3, the implementation team has developed a standard operating procedure (SOP) for Quality by design, including risk management and a template for writing a risk management plan. Rienstra: ‘These considerations are now brought together in one plan, where they used to be in different places.’ 

The new GCP version includes a new chapter on Data Governance, addressing data integrity, data flows and the control of all data. It states that computerised systems must be validated and that an audit trail must be available for all data and metadata necessary to reconstruct a particular event. Rienstra: ‘None of this was particularly new to us, because this is already included in the EMA guideline for computerised systems and electronic data in clinical trials, which has come into effect in 2023. That’s another advantage of R3: the various guidelines are now much more aligned with each other.'

CHDR had already implemented several of the innovations in R3, but in GCP, details matter. To implement R3, a working group conducted a gap analysis. This group included several people involved in CHDR's operations, in addition to the compliance team. For each section of GCP, the impact on operations and procedures was examined and the adjustments that had the highest priority were identified. Everything with a high and medium priority has now been implemented and a plan was made to implement all the low-priority changes. Rienstra: ‘An example of those low-priority changes is the replacement of the word ‘subject’ with ‘study participant’ in all our standard operating procedures. We will definitely do that when the procedure is due for an update, but it is not the highest priority, as the old terminology is clear enough. So, in the implementation, we have applied the same pragmatism that underlies GCP: seeing whether it fits the purpose. And the core purpose of our efforts is and will always be to ensure that each study is safe for participants and generates reliable data.'