DARQA GCP-event: Quality by Design and Risk-based Quality Management in Clinical Trials

The Quality by Design (QbD) and Risk-Based Quality Management (RBQM) in Clinical Trials GCP-event took place on 04 September 2026. Approximately 45 enthusiastic professionals participated in this interactive event. Eveline Krijger, chair of the DARQA, opened the event and introduced each presenter’s background information and a short introduction to the topic of each session.

Henrieke de Bie, Consultant Quality & Culture at Beyond Compliance, started the event with an exercise to activate our ‘creative thinking’ into ‘critical quality thinking’. This mindset is important to better understand and implement the RBQM which has been introduced by ICH E8 (R1) and the ‘proportionate risk-based approach’ by ICH E6 (R3) to develop the Quality Culture in the design and conduct of clinical trials.

Leire Zúñiga, Managing Director at Pharmity and CSO / CQO at Qlarix, explained the practical methodology to make RBQM work in the design and conduct of the clinical trials. She explained step-by-step from Quality by Design and Critical to Quality Factors (CtQFs) how proportionate Sponsor Oversight can be performed in compliance with ICH E6 (R3). It starts with the protocol design, followed by defining the CtQFs. If the CtQFs are well-defined, the risks can be defined, which supports the sponsor oversight and avoids micro-management.

Furthermore, she explained that even though CtQFs sound like it is a QA activity, the clinical trial team is the owner and should define the CtQFs. The intention of the RBQM approach is a pro-active approach in clinical trials and not a reactive approach. It is therefore important to start with the CtQFs prior to the final protocol (at the protocol synopsis stage).

The approach to understanding which CtQFs are most important was explained by a picture of a bridge. The main pillars of the bridge are the most critical factors, the other pillars are less important. The CtQFs are mainly the critical data and critical processes within the protocol.

Leire ended her presentation with five important messages to remember:

1.     RBQM starts with QbD, not a risk register.

2.     CTQFs define what matters most.

3.     Risks should describe what could threaten those CTQFs, and why.

4.     Evaluation and controls should drive proportionate action.

5.     RBQM must remain dynamic and visible through sponsor oversight.

After the clearly explained theory of the RBQM and CtQFs, Natalia Buchneva, Risk Management Lead at UCB, provided the pragmatic approach how to implement the RBQM and CtQF principles into practice. It was explained that, over recent years, the volume of data collected in clinical trials has increased significantly, with current trials collecting approximately seven times more data than several years ago. This increase highlights the importance of focusing on the data and processes that are critical to participant safety and the reliability of trial results.

By defining the CtQFs during the design phase of a clinical trial, the associated risks can be identified and assessed at an early stage. Appropriate risk mitigation measures can then be incorporated into the relevant clinical trial plans, enabling monitoring and oversight activities to focus on the aspects that are most critical to participant safety and data integrity. This risk-based approach supports the efficient conduct of a high-quality clinical trial. Various practical examples were provided during the presentation to illustrate this approach. Natalia concluded the presentation with the message that QbD is a systemic approach to building quality into the clinical trial from the start, which will reduce trial failures and improve efficiency.

After the lunch break it was time to practice the RBQM and CtQFs approach in small working groups. During this exercise a trial case was provided for which the CtQFs had to be defined. The working groups experienced that it requires exercise to get the right mindset for critical thinking to define the CtQFs and not confuse the CtQFs with the risks. The enthusiastic participation in the exercises resulted in good discussions.

It was concluded that the CtQFs are very helpful for clinical trial conduct and oversight.

The final presentation was provided by Coree Foreman, Owner & Principal Consultant at Q-STAR Consulting and focused on the “challenges to getting it right.”

Coree provided practical examples of CtQFs applied in clinical trials and emphasized the importance of effectively communicating the identified CtQFs and associated risks to all relevant trial team members and clinical site staff. A case study was presented, in which Coree explained the route from protocol requirement, to CtQF identified, risks, mitigations, issues, Quality Issue and Root Cause Analysis back to improvement of mitigations.  She also provided useful real-world examples of ways RBQM can go wrong, such as a siloed approach to RBQM or unclear responsibilities. The awareness of the CtQFs and the right implementation of risk management will support the overall trial quality and data integrity.

The day ended with a Question & Answer session. The event was very successful and interactive, bringing together an enthusiastic group of quality-minded professionals.