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FDA Presentations at MHRA/HC/FDA GCP Workshop 2022

These 7 presentations from the joint regulatory authorities earlier this year are useful because they reflect the FDA’s latest thinking on aspects of clinical trial conduct and reporting, and set out what’s important when it comes to Good Clinical Practice (GCP) and Risk-Based Quality Management (RBQM). The presentation titles are:

  1. COVID-19 Impact

  2. Quality by Design (QbD) in Clinical Trials

  3. Bioresearch Monitoring (BIMO) Inspections to evaluate date reliability in studies using Real World Data (RWD) and Real World Evidence (RWE)

  4. Have regulatory expectations changes as a result of the pandemic?

  5. Potential uses of Artificial Intelligence (AI ) and Machine Learning (ML) in Clinical Trials

  6. 2021 FDA Guidance Development: Clinical Trial Conduct and Reporting

  7. An update on FDA’s inspections and use of Remote Regulatory Assessments for Bioavailability and Bioequivalence studies


Below is a brief review of the key points from each presentation.


1. COVID-19 Impact


Obviously there were well-documented challenges with quarantines, site closures, travel restrictions and supply chain interruptions, but there were also wider challenges the FDA faced with such as unproven drugs with fraudulent claims. Clinical trial conduct changed during the pandemic with changes in practice such as remote consenting, electronic data capture, virtual visits, and remote outcome assessments. It also forced an increase in RBQM activities such as risk-based monitoring, and remote and central monitoring. GCP compliance remained important and ensuring the safety of trial participants “is paramount”. The FDA also emphasized that documentation is key, and that Sponsors should optimize the use of central and remote monitoring programs to maintain oversight of clinical sites.


2. Quality by Design in Clinical Trials


Starting with the importance of quality in clinical trials, and the need for quality management to “provide assurance of protection of trial participants, data are reliable, and results are credible”, the presentation goes on to cover key points from ICH E8(R1), E6(R2), and E6(R3). In E8(R1) it emphasizes that a “one size approach” to Quality by Design (QbD) does NOT fit all clinical trials and sets out the five key approaches to identifying Critical to Quality. On E6(R2) they stress that Sponsors are responsible for trial oversight and should use systematic, prioritized, risk-based approaches to monitoring trials. On E6(R3) they cover the overarching principles, including risk-based approaches and proportionality. To demonstrate the concept of QbD they use a case example titled “Ensuring eCRFs are Fit for Purpose and Designed According to the Protocol”.


3. Bioresearch Monitoring (BIMO) Inspections to Evaluate Data Reliability in Studies Using Real World Data (RWD) / Real World Evidence (RWE)


This presentation gives a background on the use of RWD/RWE for regulatory decision-making by the FDA, and important considerations and challenges when conducting BIMO inspections and data audits to evaluate RWD reliability. It highlights key points from the FDA guidance on RWD and RWE related to BIMO such as inspections, study conduct, and data reliability assessments. They provide a hypothetical inspection case example for an RWE submission.


4. Have Regulatory Expectations Changed as a Result of the Pandemic?


The first part of this presentation covers the clinical trial challenges raised by the pandemic, and the changes in approach such as the increased use of technology and remote assessments and monitoring. It covers the changes in GCP inspections that occurred, and the expectations for research conducted during the pandemic. Perhaps more interestingly it covers changes to research and regulatory oversight moving forward, including: the increased use of technology in the following areas: in Decentralized Trials (DCTs); at clinical sites (e.g. obtaining consent); by sponsors for site qualification, training, and remote monitoring; and by the FDA for Remote Regulatory Assessments (RRA) and electronic data review.


5. Potential Uses of Artificial Intelligence (AI) and Machine Learning (ML) in Clinical Trials


This interesting presentation starts with an introduction to AI and ML and draws a clear distinction between the two, even though the two terms are often used interchangeably. ML is a subset of AI that allows computer algorithms to learn and improve automatically through data without being explicitly programmed to perform a task. The presentation looks at the potential uses of AI in healthcare domains, drug discovery and development, and it’s uses in clinical trials. It also covers some of the concerns about using AI, such as ethical issues, and the considerations for GCP compliance such as data integrity, hiring skilled personnel and the development of regulations and guidance.


6. 2021 FDA Guidance Development: Clinical Trial Conduct and Reporting


The FDA Center for Drug Evaluation and Research (CDER) issued over 80 draft and final guidance documents in 2021, many including recommendations on aspects of clinical trial conduct and reporting. This presentation highlights some of the key documents, including on Sponsor and Investigator responsibilities, digital health technologies for remote data acquisition, RWE/RWD evidence, and submitting standardized study data, all of which are important from an RBQM perspective.


7. An update on FDA’s inspections and use of Remote Regulatory Assessments for Bioavailability and Bioequivalence studies


This presentation introduces the Office of Study Integrity and Surveillance (OSIS) and its mission and vision (to improve the public health by protecting study subjects and promoting properly conducted studies). It looks at RRA approaches and includes stats on the number of RRA and inspections conducted. While there is a return to travel post-pandemic, it’s clear that RRAs will remain a critical tool going forward.