An electronic trial master file (eTMF) is a trial master file in electronic (digital content) format. It is a type of content management system for the pharmaceutical industry, providing a formalized means of organizing and storing documents, images, and other digital content for pharmaceutical clinical trials that may be required for compliance with government regulatory agencies. The term eTMF encompasses strategies, methods and tools used throughout the lifecycle of the clinical trial regulated content. An eTMF system consists of software and hardware that facilitates the management of regulated clinical trial content. Regulatory agencies have outlined the required components of eTMF systems that use electronic means to store the content of a clinical trial, requiring that they include: Digital content archiving, security and access control, change controls, audit trails, and system validation.
History and background
In order to comply with government regulatory requirements surrounding BioPharma clinical trials, every organization involved in regulated clinical trials must maintain and store certain 'essential documents' related to the clinical trial to ensure regulatory compliance. Depending on the regulatory jurisdiction, this information is typically stored in the trial master file or TMF. The TMF has historically been composed primarily of paper documents, images and media captured centrally in physical file cabinets.
In order to lower costs and to expedite the clinical trials approval processes, government agencies involved in regulating clinical trials such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have been developing technology initiatives. In the U.S., the FDA created regulation CFR 21 Part 11 which supports the use of electronic records, digital media and digital signatures in clinical trials. In Europe, the European Medicines Agency has issued policies that support the use of digital signatures in clinical trials.
In clinical trials and healthcare, enterprises with manual paper-based systems are seeking to transition to automated electronic enterprise content management (ECM) systems to ensure higher levels of regulatory compliance for reduced business risk. As a result of the FDA's Part 11 policy supporting the use of electronic records and digital signatures in lieu of paper, US organizations involved in U.S. clinical trials can move from a paper-based TMF to an electronic TMF (eTMF), and still be in compliance with FDA regulatory policies.
Definition
The definition of what comprises an eTMF is defined by the regulatory agency with jurisdiction over the clinical trial. In Europe, the EMA has recently defined an eTMF as follows: 'An eTMF can contain digital documents in their original format, potentially with digital signatures, or records that have been converted from another format, such as paper documents that have been converted to digital images, which may contain wet-ink signatures. The metadata applied to documents is recommended be formally defined to ensure consistency across all documents.' At the time of this article no formal US FDA requirement exists for the use of an eTMF system in a clinical trial. However, if a clinical trial elects to store trial master file 'essential documents' in electronic format, then the eTMF system used to store those files is subject to regulatory controls specified under FDA Title 21 CFR Part 11.
Required components of an eTMF system
With respect to the FDA, the required components, controls and policies for an eTMF used in US based clinical trials follow US FDA CFR 21 Part 11 requirements. In August 2003, the FDA issued additional guidance to the industry that outlines the required components, controls, policies and validation required for electronic systems and electronic signatures. According to the FDA, systems used to store electronic records or documents are generally subject to the following controls and requirements: