The Food and Drug Administration (FDA) has released a draft guidance titled, “Good Clinical Practice (GCP) E6(R3),” explaining how the Agency plans to apply its regulations to modern clinical trial designs.

The guidance was drafted in collaboration with the International Council for Harmonisation (ICH) to “provide a unified standard to facilitate the mutual acceptance of clinical data for ICH member countries and regions.” It revises a 2018 guidance to provide clarity on FDA’s expectations around clinical trials in order to help encourage more innovative and efficient trial designs.

GCP harmonization

FDA is a founding member of ICH, dating back to 1990, and implements all ICH guidelines as FDA guidance.[1] ICH was founded as a nonprofit to bring regulatory authorities across the globe together and establish harmonized regulatory approaches to pharmaceutical regulation. Harmonization in regulation helps improve efficiency and predictability in the review process, which in turn reduces the time, cost, and patient burden of drug development.

The R3 update and earlier versions of GCP E6 focus on the design, conduct, documentation, and reporting in human clinical trials. These guidelines were developed with consideration of best practices used by the EU, Japan, the US, Australia, Canada, Nordic countries, and the World Health Organization. FDA and ICH’s release of these guidelines aims to help industry better understand what FDA and other regulators prioritize when reviewing the clinical trials in support of new drugs.

R3 update

The R3 update to the GCP E6 guidance seeks to bring past GCP principles into the modern world where trial designs are becoming increasingly innovative.

M. Khair ElZarrad, director of the FDA’s Center for Drug Evaluation and Research’s Office of Medical Policy, noted, “These draft recommendations were developed with the aim to streamline trials, making them more efficient and flexible as the trial enterprise continues to evolve.”

The R3 update explains that a risk-based approach should be used for various aspects of clinical trial design and conduct, such as data collection, monitoring, and quality management. FDA’s support of risk-based approaches means that those conducting studies have the flexibility to allocate resources and efforts toward areas of greatest impact to subject safety and study integrity.

Another notable area that the R3 update addresses is the use of digital health technologies (DHTs) in clinical trials. FDA and ICH point out that DHTs have the potential to support more efficient approaches to trial design and conduct. DHTs, such as wearable sensors, allow for the collection of a wide variety of data that was not previously possible. For example, a wristband that monitors sleep could allow investigators to constantly monitor sleep patterns of trial participants at home, whereas previously, such monitoring would have been limited overnight stays at a clinic.

The R3 update also puts emphasis on baking quality into clinical trials, or quality by design. The document states, “Quality by design should be implemented to identify the factors (i.e., data and processes) that are critical to ensuring trial quality and the risks that threaten the integrity of those factors and ultimately the reliability of the trial results.”

FDA and ICH encourage trial sponsors to be proactive during the early design phases of trials to ensure those trials are designed in ways that will allow for efficient conduct and “avoid unnecessary complexities.”

Success in other harmonization efforts

FDA recognizes that alignment across international regulatory authorities is beneficial to supporting drug development and ultimately protecting public health.

On the drug side, CDER and CBER are actively engaged in a number of pharmaceutical-focused efforts in addition to ICH, such as International Pharmaceutical Regulators Programme (IPRP), the Pharmaceutical Inspection Co-operation Scheme (PIC/S), Asia-Pacific Economic Cooperation (APEC), and International Coalition of Medicines Regulatory Authorities (ICMRA).[2]

On the medical device side, CDRH supports international harmonization efforts through its work with the International Medical Device Regulators Forum (IMDRF); Medical Device Single Audit Program (MDSAP); and Japan’s Ministry of Health, Labour, and Welfare (MHLW), among others.[3]

Impact and path forward

Through this R3 update to the GCP E6 guidance, FDA is very much supporting a “work smarter, not harder“ approach to clinical trials. Cost and time burdens of clinical research are significant barriers to drug development, and any opportunity to mitigate these burdens helps deliver important medical treatments to the patients who need them.

If you are conducting or planning to conduct a clinical trial, we encourage you to review this guidance and consider how the flexibilities FDA is proposing might benefit your study.

Comments on the draft guidance may be submitted to Docket FDA-2023-D-1955. For more information on adapting to this evolving regulatory landscape, please contact your DLA Piper relationship partner, the authors of this alert, or any member of our FDA practice group.

References:

[1]

https://www.fda.gov/drugs/cder-international-program/international-regulatory-harmonization

[2]

https://www.fda.gov/drugs/cder-international-program/international-regulatory-harmonization and https://www.fda.gov/vaccines-blood-biologics/international-activities/regulatory-harmonization-and-convergence

[3]

https://www.fda.gov/medical-devices/international-programs