Back to the Basics Part 1: What is an eTMF?
What is a TMF?
TMF stands for trial master file. Your trial master file is the repository for all study documentation relevant regulatory agencies require to confirm you are operating within expected parameters that ensure participant safety and process integrity. Per the EU Commission Directive 2005/28/EC 63 Chapter 4 Article 16, the TMF is a collection of documents deemed essential for monitoring and verifying the quality, conduct, and compliance of the clinical trial. It is the sole responsibility of the sponsor to know which documents are required (we will have more on that in a follow-up post). The goal of a TMF, as described by the FDA, is to ensure that sponsors and investigators are acting within the principles and guidelines of good clinical practice (GCP). In the USA, that means being aligned with the International Council for Harmonisation Good Clinical Practice (ICH-GCP) guidelines.
Depending on the geographical location of the trial, there may be different regulations and requirements set forth by national and local governments. The bottom line, if and when your research is subject to an inspection, you must have the required documentation appropriately indexed in your TMF. Ultimately, the continuous and final state of the TMF should be a stand-alone file that can tell the full story of the clinical trial from author-to-archive without needing further clarification from the participating sponsor or site.
What is an eTMF
eTMF stands for electronic trial master file. It is the all-important trial master file in a digital format. Over the past decade, it has become standard in the pharmaceutical and biotechnology industries to use an electronic TMF. Global, real-time access, the ability to manage files and document workflows, collaborate, and maintain all essential metadata and audit trails are a few reasons why using a digital format is preferred by many life sciences companies, and also by regulatory agencies. The eTMF has some additional guidelines to ensure compliance. Both the EMA and the FDA have released regulations, policies, and guidelines to follow for validating the use of this electronic format, the most widely followed being CFR 21 Part 11. The overall goal of the eTMF and TMF are the same: to house and maintain all required documentation for a clinical trial.
Why is the eTMF Important?
The eTMF provides regulatory agencies a clear view of the story of a clinical trial to ensure compliance with GCP. The use of metadata offers both inspectors, and users, a powerful search capability for quick retrieval of documents. Search is one simple example demonstrating how the eTMF has process and collaboration advantages over its paper ancestor, the TMF. Furthermore, creating, uploading, classifying, and indexing documents can now all be done in a few clicks. Every operation is saved in a system audit trail to tell the full story of how a document got to where it is in real-time. This is integral for validation and security. Oversight is made easier with an eTMF because it allows teams to set up and use personalized dashboards to monitor the health of a trial. Specialized reporting features provide a better overall picture of the eTMF for completeness, timeliness, and quality.
These advantages, among many others, help to speed timelines, reduce minor and major findings, and produce a more compliant study from start to finish. Organizations are being challenged to move at speeds that were once thought impossible. The transformation of technology over the past two decades has facilitated the necessity to be more mobile, more productive, and more efficient. With the benefits of eTMF technology so widely understood, it behooves sponsors and CROs to adopt an eTMF for their present and future studies, not only to reduce their own risks, but to better align with regulatory expectations that have been updated for a digital world.
How is the eTMF Evolving?
Originally, eTMF was simply taking the paper format and translating it to a digital experience. As with all technology, things evolve quickly. Presently, eTMF technology is looked at by many organizations as the end-point to a broader clinical document management strategy, all of which lives in a single electronic document collaboration environment. The authoring, review and edit cycles, and approvals of various types of documentation all take place in one system, making it easy to capture and provide transparency into the complete history of every document. Further, it is widely recognized that mobile experiences afford additional accessibility and opportunities for more proactive oversight, and so we have seen eTMF processes such as document capture, coding, and oversight dashboards emerge. These advances have trickled into site files using similar capabilities and also extending to CRA reconciliation and remote monitoring. Perhaps the most exciting frontier in eTMF innovation right now is the role of artificial intelligence (AI) and machine learning (ML) in adding powerful process automation and predictive insights. Automatic document classification, redaction, document quality, and inspection readiness use cases are just a few of the advantages that are currently available or soon to be available. The future of eTMF will promise simpler implementation, greater ease of use, and smarter technology that will alleviate more and more administrative burden and help to bring the target of inspection readiness closer and closer and easier to hit and meet regulatory expectations.
For more information on TMF best practices and eTMF technology, contact us at firstname.lastname@example.org.