Summary: This document is helpful for building and maintaining an inspection-ready Trial Master File (TMF)—paper, electronic (eTMF), or hybrid so a trial can be reconstructed and verified without extra explanation. It clarifies what belongs in the TMF (essential documents, superseded versions, and decision-driving correspondence), how to structure and index it across sponsors, investigators/sites, CROs, and vendors, and how to keep it contemporaneous “at all times.” It’s especially useful for setting controls that prevent document loss or tampering: role-based access, audit trails, backups, metadata standards, and validated systems. The guideline also gives practical direction on managing emails and central repositories, handling certified copies and scanning/digitization (including static vs dynamic files), and performing risk-based QC checks to ensure completeness and proper filing.