The Relationship with Our “X’s”: Good Clinical Practice – One of the “X’s” in GXP
When you hear the word “GxP” in a regulated industry, the first thing that comes to mind is, which regulation are we talking about from the “Good Practices”? Today our focus is on Good Clinical Practice (GCP) as the Food and Drug Administration (FDA) recently released the revised guidance, “E6(R3) Good Clinical Practice, Guidance for Industry” on September 8, 2025. This revision incorporates flexible, risk-based approaches and embraces innovations in trial design, conduct, and technology with the focus on quality by design, participant protection, and the reliability of trial results [1] .
Scientific studies in our industries for human investigational drugs, biological products, and medical devices are regulated by the FDA to support safety and effectiveness prior to being marketed for public use [2] . The FDA’s top priority is safeguarding the rights, safety, and welfare of individuals in these trials to ensure that they are provided informed consent and transparency, as well as overseeing the studies and making sure they are designed, conducted, reviewed, and reported according to regulations and GCP. The FDA uses their Bioresearch Monitoring (BIMO) program [3] to perform these onsite inspections and data audits. So where does the International Council for Harmonisation (ICH) come into all of this?
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is an international non-profit organization established in 1990 that brings together regulatory authorities and the pharmaceutical industry to harmonize drug development standards globally. The ICH’s goal is to ensure that medicines are safe, effective, high-quality, and efficiently registered worldwide [4] . The ICH developed the E6 (Efficacy) guideline [5] which was adopted on January 6, 2025.
GCP is an international, ethical, scientific, and quality standard for designing, conducting, recording, and reporting clinical trials involving human subjects. The E6 guideline serves as a global reference for regulatory authorities, sponsors, investigators, and other stakeholders. Here is a summary of what the R3 revision includes:
Flexibility for innovative trial designs such as decentralized and adaptive trials and the use of digital technologies for data collection and monitoring.
The guidance emphasizes critical thinking risk-based approaches to ensure trial quality, shiftingfrom rigid procedural compliance to identifying and managing factors that could impact patient safety or data integrity.
There is a focus on ensuring the integrity, reliability, and traceability of data with clear expectations for electronic records, data sharing, and audit trails.
The guidance reinforces requirements for protecting trial participants, including procedures for informed consent, privacy, and ongoing safety monitoring.
Responsibilities are clearly defined for sponsors, investigators, and ethics committees to help ensure accountability across all aspects of trial conduct.
Key Principles of the E6(R3) Final Guidance:
Ethical Conduct – Clinical trials must adhere to ethical principles that originate in the Declaration of Helsinki and ensure respect for participants’ rights and safety (e.g., Informed Consent, independent review by the Institutional Review Board – IRB/Independent Ethics Committee – IEC, etc.).
Scientific Validity – Trials should be scientifically valid with robust protocols and appropriately justified methodologies.
Risk – Resources and oversight should be proportionate to the risks and potential benefits associated with the trial.
Documentation and Records – Accurate, timely, and secure documentation is required for regulatory review, data verification, and participant protection.
Continuous Improvement – The guideline encourages ongoing evaluation and improvement of processes considering past lessons learned and emerging best practices.
With this revision release, sponsors, investigators, and research organizations must review and update their policies and procedures to align with the new requirements. The FDA’s adoption of ICH’s GCP E6(R3) represents a shift forward to clinical trial conduct, emphasizing flexibility, risk management, and participant protection as well as supporting a culture of continuous improvement, ethical conduct, and scientific rigor. By understanding and implementing these points, clinical research professionals can contribute to more efficient, ethical, and high-quality trials that ultimately benefit trial participants in the discovery of new therapies impacting communities’ quality of life.
Reference
[2] https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/good-clinical-practice