On January 6, 2025, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) issued its final version of the “Guideline for Good Clinical Practice E6(R3)”. This revision – the first major update in nearly a decade – marks a pivotal shift in how clinical trials are designed, conducted, and overseen.

In a recent webinar hosted by PCM Trials, regulatory, legal, and operational leaders came together to unpack the implications of this update and share strategies for proactive adaptation. Moderated by Deb Guattery, a seasoned quality expert at PCM Trials, the panel explored how ICH GCP R3 is reshaping the regulatory landscape and how sponsors and service providers alike can proactively adapt.

Why R3, and why now?

Josh Ryon, Associate Director of Project Management Execution at PCM Trials, opened the discussion with an overview of the guidance’s evolution, noting that after 20 years of relative stability, the landscape shifted dramatically: “The industry is innovating at a quicker pace than the available regulations. In the last decade in clinical research, we’ve seen exceptional development in available technologies, in innovative trial design, and approaches that probably were not considered even 10 years ago.”

R3’s emphasis on quality by design, risk proportionality, and fitness for purpose marks a shift toward more adaptive, patient-centric trial models that reduce participant burden while maintaining precision. As Ryon explained, “Taking the time upfront to integrate quality into the protocol will build efficiencies and mitigate risks later.”

Global framework, local execution

With trials now spanning more countries than ever, Maryleen Lovell-Petronilia, Quality Assurance Manager at Clinical Trial Service (CTS), highlighted the importance of balancing global standards with country-specific nuance. “[At CTS], we oversee the conduct of clinical trials in over 80 countries…that’s why it’s so important to focus on both the global aspect and the local regulatory landscape.”

She noted that R3 reflects a shift from a one-size-fits-all mindset to a more flexible framework that reflects the complexity of today’s decentralized and hybrid trials: “What we’re seeing now with the shift from R2 to R3 is the flexibility to have a more adaptive trial design, which goes hand in hand also with proportionality and risk management.”

Pharmacovigilance and data oversight in the digital era

Julie Keersmaekers, Associate General Counsel, Data Privacy at PCM Trials, underscored how R3 modernizes GCP to reflect today’s digital realities, placing greater emphasis on safety monitoring and data governance: “We have a robust data protection and data privacy program at PCM Trials… but historically, decentralized elements have not often been explicitly referenced in guidance. So, we have had to ensure that we are adhering to the regulations, but work within a bit of a gray area. [R3] is helpful because it brings GCP in line with the reality of the digital world.”

Proactive collaboration is key

Throughout the conversation, one theme came through loud and clear: adapting to R3 isn’t about reacting, it’s about preparing. Keersmaekers pointed to the importance of early collaboration in the research process: “Sponsors should engage us early. The more we can collaborate from the start, the more likely we are to build quality into every layer of the trial.”

At PCM Trials and CTS, that proactive approach is already underway. Lovell-Petronilia shared how CTS’ quality team is updating SOPs and internal trainings to align with the new guidelines, while also helping educate site partners. Ryon emphasized operational readiness as well: “We’ve worked closely with our quality team and with our legal team to understand what these guidelines are framing… We want to work proactively to get alignment with the sponsor and the service providers.”

Looking ahead

At the heart of the ICH GCP E6(R3) revision is a recognition that clinical research must be as adaptable, transparent, and patient-centered as the world it operates in.

“We’ve always prioritized innovation,” said Keersmaekers. “But R3 offers a framework that allows that innovation to happen more safely, more consistently, and with better alignment across stakeholders.”

As regulatory landscapes shift, PCM Trials remains committed to helping partners navigate regulatory complexity with clarity, while keeping clinical excellence and safety at the heart of every decision.

Want to learn more? Watch the full webinar here.