Designation : Managing Director PharmaLex

Susan K. Maue

Trial master files were long treated as an archive repository for all documents related to a clinical trial. That approach doesn’t properly reflect the evolving story of a study, which will go through a variety of changes and milestones throughout the product lifecycle and across different study regions.

While regulatory authorities have guidelines around the management of the TMF, this alone does not ensure inspection readiness.

To achieve completeness, timeliness and quality with the TMF there is a need for technology that can support the evolving story at any point along the way, and which, at the same time, is easy to use and integrates with other systems.

Although there is general recognition in the post-pandemic world that electronic is a necessity for the TMF, many solutions either lack the sophistication needed to support both the study evolution and, most critically, achieve inspection-readiness or require huge manual effort. PharmaLex recognized the challenges faced by our customers and saw the need for a fit-for-purpose TMF solution that would deliver a complete, high-quality set of documentation. With this realization, PharmaLex acquired TMF leader Phlexglobal to help companies get into and stay in the TMF health zone, which means completeness, timeliness, and quality.

Making your eTMF inspection-ready

Regulatory authorities, including the FDA, have been increasing their scrutiny of the TMF and tightening reinforcement. Inspection reports have uncovered numerous critical findings related to record-keeping, usually due to incomplete TMFs or poor-quality documentation, inadequate oversight and control of the study and TMF, and lack of compliance or documentation missing from the TMF.

A fit-for-purpose eTMF solution that is not restricted by limitations of the document management platform that a sponsor or contract research organization (CRO) has in place is critical. Such a solution overcomes the challenges of feeding data into the eTMF from clinical trial management systems and study start-up systems by connecting into those platforms and taking data from those systems to ensure a complete, high-quality set of documentation.

In so doing, companies can be assured of an accurate and complete audit trail of their documentation and proper management of documents across various sections of the TMF, ensuring the eTMF is inspection-ready.

Addressing data transferability

One of the big challenges in study close-out is transferring the TMF from the CRO to the sponsor. Additionally, these documents remain crucial well after a study ends and after this transfer, and must be readily available for inspection.

With robust fit-for-purpose software, CROs can package the sponsor’s eTMF and very simply transfer it into another system. This mid-term, pre-archival configuration allows the eTMF to be stored in an inspection-ready state, allowing inspectors to access the eTMF directly online.

Such transferability should be aligned with the global standards development organization, CDISC, which announced official affiliation with the Trial Master File (TMF) Reference Model Group in April 2022. 

To support the exchange of TMF content and create commonality across platforms, a sub-group from the TMF Reference Model developed an eTMF Exchange Mechanism Standard (EMS).Importantly, PhlexTMF supports the EMS, removing the need for convoluted mapping and manipulation when transferring the TMF between stakeholders.

“Having a standardized TMF structure for all documents from all studies across companies radically streamlines any document and data transfer required,” says Karen Roy, senior VP of clinical marketing at PharmaLex company Phlexglobal and Chair of the TMF Reference Model Steering Committee. “Now that we are a part of CDISC, the TMF Reference Model becoming a standard will enforce this standardization”

People. Process. Technology

One of the biggest differentiators between the PharmaLex approach to eTMF and other solutions is the flexible and adaptable design that lets clients simply license the technology and run it themselves, buy a service where PharmaLex sets up the technology, deploys it and delivers the service, or a hybrid of the two where PharmaLex helps with some parts of the process.

This approach offers the triple benefit of people, process and technology. The technology, or solutions aspect, refers to having a fit-for-purpose eTMF solution that ensures the TMF is complete, of good quality, enables proper oversight and provides a complete and clear audit trail for inspectors.

For the eTMF technology to attain the goal of achieving the TMF health zone, it also needs to be underpinned by people and processes, which can be delivered through deploying PharmaLex’s services. This delivers guidance from experts in TMF best practices, regulatory standards as well as the technology itself to improve productivity, efficiency and quality. It also ensures expert processing services to achieve completeness, timeliness and quality of the TMF at every stage of the study. (see graphic below)

Keys to successful management of the TMF include:

• Have staff dedicated to the TMF

• Ensure in-house TMF experience and expertise for internal TMF management as well as CRO oversight

• Provide comprehensive and regular training on SOPs, TMF technology and document management processes

• Stay current on the latest regulatory guidance related to the TMF

• Identify barriers affecting collaboration with internal and external teams working on the TMF

• Ensure SOPs are aligned with requirements and ensure all stakeholders interpret SOPs the same way

• Conduct regular internal TMF audits and site audits

• Obtain executive buy-in on the importance of the TMF

The last point, executive buy-in, is one of the biggest barriers for companies trying to adopt a comprehensive eTMF solution. There has to be a top-down organizational commitment so all functional groups involved with the study make it their objective to contribute to a complete, high-quality eTMF. As a company committed to helping sponsors and CROs achieve this objective through our technology and services, PharmaLex can help to address the compliance challenges that have proven to be an ongoing issue for companies.