Author: AlmiraAdmin

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.

Machine translation: this English text was automatically translated from the original Dutch article. If anything is unclear or differs, please refer to the Dutch original.

Event language: This event was held in Dutch.

On 28 November, DARQA’s GLP Committee organised a theme day on a topical subject: the connection between Good Laboratory Practice (GLP) and IT security. The event was prompted by the publication of the latest OECD document, No. 25, entitled “Good Laboratory Practice and IT Security”. As is customary when new OECD publications appear, the Dutch Health and Youth Care Inspectorate (IGJ) was also present.

The meeting attracted around 50 participants, including new DARQA members and several visitors attending a DARQA event for the first time.

Secure storage of GLP data

The day began with a presentation by Frans Boeijen, who addressed the question: How do you safeguard electronic GLP data? He outlined the similarities between measures for paper and digital data and emphasised additional steps for optimal protection, such as incident recording, penetration testing, and backup and restore procedures, alongside familiar measures such as firewalls and antivirus software.

Improving QA audits with OECD GLP Document No. 25

John Cheshire of Headway Quality Evolution Ltd joined as an external speaker. He provided an overview of QA responsibilities in the various OECD GLP documents and explained the link with Document No. 25. He also offered practical questions that QA professionals can ask during audits based on this document.

Cyberattack: what now?

Frans Brouwer then guided the participants through a realistic scenario: a cyberattack on a GLP laboratory. Working in groups, they considered the steps needed to get “back in business” after such an incident. The session produced valuable insights into crisis management and recovery planning.

Practical examples from the IGJ

After lunch, IGJ inspector Mirjam Smeets presented a series of real-world examples of what can go wrong when electronic data are managed. It was an instructive overview that made clear just how crucial care and awareness are.

Panel discussion: from patching to the human firewall

All speakers, including Hans de Raad, took part in a lively panel discussion. Topics included:

• How should differences between global and local User Requirement Specifications be handled?
• What are the requirements for patching operating systems?
• How should the frequency and scope of backups be determined on the basis of risk?
• How can behavioural analytics support intrusion detection?

The human factor also received considerable attention: many incidents are caused by human actions. Training and awareness are therefore indispensable—the “human firewall” is at least as important as technical safeguards.

Q&A with the inspectors

The concluding Q&A covered questions including the validation of Excel spreadsheets. The advice was to avoid Excel for generating GLP data, but to use it for analysing existing data only when it has been validated. The role of the Archivist in cloud storage and the importance of clearly allocating responsibilities between IT and archiving were also discussed.

Main conclusion

All presentations showed that IT security measures in GLP environments are primarily intended to reduce the risks of data loss or damage. Every organisation must be aware of these risks and take appropriate measures to achieve and maintain compliance.

The day ended with informal drinks, providing ample opportunity to exchange knowledge and experiences—exactly as DARQA intended.

Frans Brouwer

Chair, GLP Committee

Machine translation: this English text was automatically translated from the original Dutch article. If anything is unclear or differs, please refer to the Dutch original.

Event language: This event was held in Dutch.

On 16 May 2025, the GCP Committee organised an informative and interactive theme day centred on Revision 3 of ICH E6 GCP. As announced beforehand, this was not a GCP training day, but a day intended for exchanging views on the changes brought about by implementing ICH GCP R3.

The day was opened by DARQA chair Eveline Krijger. This was followed by a clear presentation on the history of R3 and the pillars on which the new version is built.

After this introduction by Henrieke de Bie on behalf of the GCP Committee, the programme continued until lunch with two presentations entitled “Implementing R3: Where to Begin?” Michael Smith explained the implementation plan from a sponsor’s perspective, while Edith Schafsfoort discussed what R3 means for the investigator. Both presentations clearly showed that each party faces its own challenges and that the transition from R2 to R3 involves a great deal of thought and additional documentation. R3 frequently uses the terms “fit for purpose” and “risk based”; the study team must therefore document its considerations and rationale throughout.

After lunch, QA’s perspective was addressed. Kees van der Ploeg explained how his organisation made choices concerning the implementation of risk-based QA.

The plenary session was led by Joke van Wageningen, and the day concluded with a Q&A session featuring two IGJ inspectors. This Q&A was again chaired by the DARQA chair. DARQA members had been able to submit questions well before the event, and during the session the inspectors explained the IGJ’s view. It is important to note that R3 applies not only to studies started on or after 23 July 2025. The IGJ also expects organisations to demonstrate implementation activities for studies already under way.

All in all, it was a dynamic and engaging day, which ended with enjoyable informal drinks.

Machine translation: this English text was automatically translated from the original Dutch article. If anything is unclear or differs, please refer to the Dutch original.

Event language: This event was held in Dutch.

On 7 November 2025, impurities took centre stage during the annual GMP Theme Day, and several Dirty Secrets were revealed.

One presentation addressed the development of a holistic Contamination Control Strategy using a CCS tool.

Impurities also play an important role in the early development of a product. This was explained in greater detail from a CMC perspective. 

Impurities can originate not only from the product itself, but also from manufacturing materials or primary packaging, entering the product in the form of Extractables & Leachables.

After the break, the programme continued with a presentation on Elemental Impurities that included an enjoyable quiz. The winner went home with a delicious chocolate letter. 

The selection and management of CMOs in relation to technology transfer were then discussed.

Several presentations from the ECA conference on Annex 22 were summarised, prompting the question: is AI the future?

The day concluded with an update on ICH Q5, followed by a case study and panel discussion on “Impurities in the Spotlight—GMP’s Dirty Secrets”.

It was a successful day, offering insights from several perspectives into how to identify, reduce and prevent product impurities.