Clinical Trial Systems: Trial Master File (TMF) and eTMF, & FDA’s Recent Draft Guidance for Electronic Records/Signatures Used in Clinical Trials

Overview:

Organizations involved in the conduct of human clinical trials must meet rigorous regulatory expectations across global jurisdictions. These expectations are not only legal requirements but also form the backbone of ethical, high-quality research and product approval processes. Central to this compliance ecosystem is the Trial Master File (TMF) — a structured collection of essential documents that demonstrate the sponsor’s adherence to regulatory, procedural, and ethical standards throughout the lifecycle of a clinical trial.

Depending on the region, the TMF (or electronic TMF/eTMF) must be designed and maintained to allow inspectors and auditors to reconstruct the trial’s progression and data integrity at any point in time. In the United States, the Code of Federal Regulations (21 CFR 312.50) makes it clear that sponsors are responsible for ensuring that investigations are conducted in accordance with approved investigational plans. While the FDA doesn’t mandate a TMF per se, companies operating under ICH Good Clinical Practice (GCP) guidelines are required to establish a TMF to comply with expectations for trial oversight, data quality, and documentation.

The European Union, under Directive 2005/28/EC, explicitly mandates the maintenance of a TMF composed of “essential documents” — those that enable both the conduct of a clinical trial and the evaluation of the quality of the resulting data. Section 8.1 of the ICH GCP guidance further clarifies that these essential documents must, both individually and collectively, support the credibility of the trial and regulatory decision-making.

The ICH’s 1996 publication of consolidated GCP guidance brought harmonization across the US, EU, and Japan — promoting mutual recognition of clinical data and strengthening global regulatory alignment. As a result, the TMF has become a de facto standard for demonstrating compliance and accountability across pharmaceutical, biologic, and medical device development pipelines.

In today's digital environment, electronic systems and electronic signatures have become integral to clinical operations. However, this digital shift introduces new challenges related to data reliability, audit trails, and system validation. Recognizing this, the FDA issued a March 2023 draft guidance updating its previous positions on the use of electronic records and electronic signatures (ER/ES) in clinical investigations, aligning these systems with the requirements of 21 CFR Part 11. This updated guidance provides clarity to sponsors, CROs, and IRBs on the conditions under which electronic systems are considered trustworthy and compliant with FDA expectations — especially regarding clinical trials involving medical products, tobacco products, food, and animal drugs.

While this latest draft does not impose new regulatory obligations, it represents the FDA’s most current thinking on how to design, validate, and operate digital systems used in clinical trials — with implications for TMF systems, clinical databases, and connected GxP systems. The expectation is clear: electronic systems must be validated, documented, and managed under a risk-based approach to ensure data integrity and audit-readiness.

This session will provide attendees with a comprehensive roadmap to managing both paper-based and electronic TMFs in compliance with US and global regulations.

Whether you are a clinical operations lead, QA/RA professional, CSV/IT specialist, or sponsor/CRO project manager, this webinar will equip you with the knowledge to strengthen your compliance posture and ensure your TMF and related clinical systems can withstand regulatory scrutiny.

Areas covered in the session:

• GxP Data and Computer Systems Regulated by FDA
• Computer System Validation (CSV)
• Computer Software Assurance (CSA)
• The System Development Life Cycle (SDLC) Methodology
• Risk Assessment
• GAMP®5 Software Categorization
• GAMP5, 2nd Edition
• Validation Strategy and Planning
• Functional Requirements Specification (FRS)
• Design/Configuration Specifications
• Installation Qualification (IQ)
• User Acceptance Testing (UAT)
• Maintenance and Operational Support of FDA-Regulated Computer Systems
• Policies and Procedures to Support CSV
• Training and Organizational Change Management (OCM) Supporting CSV Activities
• Trial Master File (TMF) background and rationale
• Electronic TMF (eTMF)
• The essential documents to include in a TMF
• Organizing and maintaining a TMF/eTMF
• Recent FDA Draft Guidance for 21 CFR Part 11 (ER/ES) Compliance for Clinical Trial Systems
• Standard Operating Procedure required to support TMF/eTMF
• Inspection of TMF/eTMF records
• Q&A

Handouts included:

Attendees will receive three exclusive downloadable handouts, including:

• Essential TMF/eTMF Documents Checklist
• CSV Starter Toolkit (validation plan, risk table, SDLC map, SOP outline)
• Guide to FDA’s latest draft on electronic records and signatures

Why should you attend?

If your organization is involved in conducting or supporting human clinical trials, maintaining a compliant and inspection-ready Trial Master File (TMF) is critical. Regulatory bodies such as the FDA, EMA, and ICH regions expect sponsors to document and preserve all essential trial records — and the lack of a properly structured TMF or eTMF can lead to delays, rejections, or noncompliance findings during inspections.

This session will help you understand not just what documents need to be included in a TMF, but how they must be organized, validated, and made audit-ready — especially when managed through electronic systems. With recent updates to FDA guidance on electronic records and 21 CFR Part 11 compliance, it's more important than ever to ensure your systems and documentation practices meet evolving expectations.

You’ll gain practical insights on aligning your TMF and GxP systems with global regulatory frameworks, while also learning how to apply validation strategies like Computer System Validation (CSV), Computer Software Assurance (CSA), and GAMP®5 principles. Whether you're using a paper-based or digital TMF, this webinar will help you prepare for regulatory scrutiny with confidence and clarity.

What industries will benefit from your training:

Manufacturing, Testing, Packaging and Distribution companies in the following industries that are regulated by FDA are required to follow GxPs:

• Pharmaceutical (for drug products introduced using a medical device)
• Medical Device
• Biologicals (for biological products introduced using a medical device)
• Tobacco (based on the Tobacco Control Act of 2009)
• E-Liquid/Vapor (based on the “Deeming” Act of 2016)
• E-Cigarette (based on the “Deeming” Act of 2016)
• Cigar (based on the “Deeming” Act of 2016)
• Third-Party companies that support those in the above industries, including Contract Research Organizations (CROs)
• Colleges and Universities offering programs of study in Clinical Trial Management and Regulatory Affairs/Matters related to FDA

Who will benefit?

Personnel in the following roles will benefit:

• Information Technology (IT) developers, testers, support resources
• QC/QA Managers
• QC/QA Analysts
• Clinical Data Managers
• Clinical Data Scientists
• Analytical Chemists
• Compliance Managers
• Laboratory Managers
• Automation Analysts
• Manufacturing Managers
• Manufacturing Supervisors
• Supply Chain Specialists
• Computer System Validation Specialists
• GMP Training Specialists
• Business Stakeholders responsible for computer system validation planning, execution, reporting, compliance, maintenance and audit
• Consultants working in the life sciences industry who are involved in computer system implementation, validation and compliance
• Auditors engaged in the internal inspection of labeling records and practices