3 Takeaways from BeiGene and J&J on TMF Regulations and Inspections
TMF leaders are navigating changing regulations and inspection approaches, including hybrid and multi-agency inspections. More than 2,000 people attended the Veeva R&D and Quality Summit in Boston this fall, including TMF leaders who shared insights into how their function can keep pace with the changes. Here are three takeaways from two TMF leaders: Jamie Toth, BeiGene’s senior director of TMF management and records, and Heather Frankhouser, J&J Innovative Medicine’s associate director of clinical trial management solutions.
Takeaway 1: TMF standardization is increasing
The TMF Reference Model is now affiliated with the Clinical Data Interchange Standards Consortium (CDISC). This signals the industry’s move toward standardization and uniformity in how sponsors set up their eTMF systems, including details like metadata expectations.
“We’re very excited about this change,” says Toth, who is also a steering committee member on the CDISC TMF Reference Model working group. “One of the biggest efforts will be bringing the TMF Reference Model out of the spreadsheet and into the CDISC library.” Frankhouser also believes this long-term strategy will improve TMF management.
Standardization could result in efficiency gains for CROs, who can expect a more consistent approach in operations across various sponsor environments.
Takeaway 2: Remote, hybrid, and multi-agency inspections are the new reality
Remote and hybrid inspections are becoming the norm, and the FDA is now teaming up with the EMA and MHRA to attend their inspections and to learn their approaches. This multi-agency approach adds layers of complexity.
“Inspectors are more focused on the TMF, including data integrity, traceability, and audit trails that they might not have been thinking about five years ago,” Toth says.
To Frankhouser, the heightened scrutiny emphasizes the importance of updating inspection readiness processes — especially concerning audit trails.
“Thankfully, we were prepared for the increase in remote inspections, as the agencies are moving more in that direction,” Frankhouser says. “Audit trails were really big for us. If you haven’t already, that’s something you should look at.”
Takeaway 3: ICH E6 (R3) will usher notable changes
ICH E6 (R3) is still undergoing changes but is likely to be finalized in 2024. From a TMF perspective, there are a few things to note comparing the new regulation with ICH E6 (R2). The following is a summary of the key changes spanning data integrity, systems, and retention rules:
- It expands on how to take a thoughtful risk-based approach to clinical trials, including TMF management, and outlines new expectations for essential and “potentially essential” records. The types of records now considered potentially essential are influenced by a broader range of factors related to the specific trial, which means sponsors and CROs must work together to decide how they define them.
- ICH E6 (R3) explicitly introduces the role of computerized systems in clinical trials, marking a first for this regulation. Investigator sites will have to ensure that their systems are “fit for purpose.”
- ICH E6 (R3) now refers to local laws for rules on document retention, which likely means that inspection sites will offload much of this responsibility onto sponsors. Consequently, sponsors will need to adapt to a variety of local regulations, potentially necessitating new processes to manage retention.
There are outstanding TMF-related gaps in the proposed regulation, such as guidance on how to document third-party oversight, on which Toth and other industry leaders provided feedback.
“The regulation was designed to encourage sponsors, clinical practitioners, and investigators to approach clinical trials with a thoughtful, risk-based approach that is guided by their specific patient population, record types, and other factors,” Toth says.
For more actionable tips to improve your TMF operations, view this checklist with nine steps to create and maintain an inspection-ready culture.