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FDA Places Quality Management at the Heart of Updated Inspection Guide

By April 11, 2022 No Comments
FDA Places Quality Management at the Heart of Updated Inspection Guide
Author: Patrick Hughes, Co-Founder & Chief Commercial Officer, CluePoints

It’s official: Risk-Based Quality Management (RBQM) is essential for the smooth running of clinical trials.

The latest version of the FDA’s Bioresearch Monitoring Program (BIMO) guide calls for quality management systems to play a more significant role – with Good Clinical Practice (GCP) inspections now placing increased emphasis on safety oversight, outsourced services, and the selection and monitoring of clinical investigators, among other factors.

The update to the BIMO handbook, which covers all aspects of the conduct and reporting of FDA-regulated research, makes a clear case for a new way of working which boosts participant safety and the likelihood of trial success.

By enabling researchers to detect data quality issues in real-time, our Risk-Based Quality Management (RBQM) technologies have proved their worth during the race for a COVID-19 vaccine when Pfizer’s trials required the processing of vast quantities of data from several global sites.

RBQM is now driving a significant shift throughout clinical research, particularly in decentralized clinical trials, by helping to speed up the drug development route without compromising data quality.
The new revisions to the BIMO guidelines, a cornerstone of the FDA pre-approval process for all new medicines and medical devices, were released in September. The ripples are being felt across the industry as a result.

A closer look at the changes

Historically, the FDA has focused on reviewing standard operating procedures (SOPs) and confirming those processes were followed. The agency now expects to see organizations taking a risk-based approach to monitoring procedures and activities, including sight of a trial’s written monitoring plan, where it was followed, and any modifications. One of the manual’s new sections on safety oversight addresses how FDA investigators will assess whether the sponsor has established and followed a risk management plan – placing RBQM at the heart of clinical trials.

A trial’s data management plan and SOPs for collecting, handling, and managing data will be closely scrutinized, as will written agreements between sponsors and CROs, CRO qualifications, and protocol-specific training given to the CRO.

To account for the increased use of remote monitoring during the pandemic, inspectors will also scrutinize the ways remote monitors access site files, including screen-sharing and direct access to electronic medical records, and assess whether the security and confidentiality of records were maintained.

Part of a broader movement

The BIMO update preceded the MHRA’s updated Good Clinical Practice (GCP) guidance on Oversight and Monitoring Activities by a matter of months – but both give prominence to the value of data quality and integrity.

The MHRA’s document, published in January 2022, included a CluePoints case study to demonstrate the value of Centralized Statistical Monitoring (CSM) as being “powerful in detecting outlying sites.” The shared case study focused on a phase II vaccine trial of 16,000 patients across 200 investigator sites in the North American, European, and Asian Pacific regions. CluePoints’ SMARTÔ engine found several sites in one country had recorded significantly lower mean body temperature measurements than those in other nations. The error magnitude, too small to be detected using traditional on-site monitoring, was revealed instantly using statistical analysis methods – enabling investigators to take swift, corrective action, replacing all defective thermometers before it could impact data quality or integrity.

Furthermore, the R3 iteration of the ICH E6 Guidelines for Good Clinical Practice, released in April 2021, emphasized quality by design, underscoring the value of a risk-based approach to encourage the more effective use of remote monitoring practices, reduce site visits, and eradicate 100% source data verification.

The benefits of RBQM

RBQM is no longer a nice-to-have; instead, it’s a must. The approach ensures studies can reliably assess the efficacy of experimental treatments to promote safety and boost success rates.

Robust RBQM solutions allow teams to centrally access information, collaborate on investigations, and document any mitigations or remedial actions, as the FDA’s new approach is called for.

The greater adoption of central monitoring allows sponsors to interrogate clinical and operational data in real-time, increasing efficiency, improving patient safety, and reducing costs. Notably, the real-time analysis checks another critical box for the FDA, which wants to see non-compliance being actively managed; this entails determining the root cause in a timely manner and testing whether corrective actions have fixed any identified issues.

RBQM solutions mean a clean dataset and a much-needed reliable audit trail for regulatory scrutiny – another critical factor outlined in the revamped BIMO rules.

Implications for the industry

The new regulatory expectations around quality management mean a renewed vigor to ensure policies, procedures, and risk management plans meet the highest standards.

A risk-based approach to quality management can ensure clinical trials are inspection-ready and empower researchers to spot issues earlier and act faster. In addition, the centralized supervision of data and risks has led to better patient engagement, diversity and retention, improved trial resilience, and enhanced data quality.

RBQM also avoids the expensive and unnecessary obstacles to approval and market, offering lower development costs and shorter timescales to unlock research benefits while maintaining regulatory compliance.

Patrick Hughes

Patrick Hughes

Patrick holds a Marketing degree from the University of Newcastle-upon-Tyne, UK, and a post-graduate Marketing diploma in Business-to-Business Marketing Strategy from Northwestern University - Kellogg School of Management, Chicago, Illinois. Responsible for leading global sales, product, marketing, operational and technical teams throughout his career, Patrick is a Senior Executive with over eighteen years international commercial experience within life sciences, healthcare and telecommunications. In the past, Patrick consulted on corporate and commercial strategy for various life sciences companies and was responsible for successfully positioning ClinPhone as the leading Clinical Technology Organization during his 10-year tenure with the company.