Ensuring inspection readiness: how Aixial Group delivers an audit-ready trial master file

The regulatory foundation of the TMF

Global health authorities are aligned in their expectations of the TMF as the primary means of demonstrating compliance and enabling reconstruction of the trial.

• ICH GCP E6 (R2) states that:

“Essential documents permit evaluation of the conduct of a trial and the quality of the data produced.” Section 8 of ICH GCP emphasises that essential documents must be complete, accurate, and maintained throughout the trial lifecycle, not created retrospectively.

Both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) reinforce this expectation through inspection findings and published guidance, consistently highlighting TMF deficiencies as a leading cause of critical observations.

• EMA expectations:
  • The TMF must be available at all times for inspection
  • Sponsors and CROs must demonstrate ongoing oversight
  • TMF management should be risk-based and proportionate

• FDA expectations:
  • The TMF must enable independent reconstruction of the trial
  • It should demonstrate compliance with 21 CFR Parts 50, 56, and 312
  • Documentation should be timely and contemporaneous, with authentic version control

At Aixial Group, these expectations are non-negotiable and directly shape how we operationalise inspection readiness.

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Clear ownership and contemporaneous filing

Despite these challenges, regulatory expectations for patient safety, benefit–risk assessment, and compliance remain unchanged. Regulators consistently cite delayed or retrospective filing as a TMF risk. In response, document ownership is clearly defined within the TMF Index, ensuring accountability at the functional level.

Our expectation is that finalised documents are filed contemporaneously, typically within 30 calendar days, by the document owner. This supports:

• ICH GCP requirements for timely documentation
• EMA expectations for inspection-ready TMFs at any point
• FDA scrutiny of document authenticity and version control

Contemporaneous filing is not just operational efficiency – it is regulatory compliance.

Data-Driven oversight and risk-based monitoring

ICH GCP E6 (R3) introduced a strong emphasis on risk-based quality management. Leveraging eTMF system data, ongoing inspection readiness and TMF health reports are provided to project teams, enabling early identification of gaps and trends.

This approach aligns with Regulators’ expectations with issues identified and addressed early, well before they become inspection findings.

Continuous quality control to meet global expectations

Quality cannot be added in at the end. A two-step quality control process is applied to all TMF artifacts:

1. Initial QC by the document owner
2. Secondary QC by a specialised TMF team

This layered review ensures alignment with internal SOPs and industry standards, and supports inspection defensibility.

Secure, validated eTMF systems

Technology underpins inspection readiness. A validated eTMF system with full audit trails, role-based access, and permission controls ensures data integrity and compliance. Access is granted only after TMF-specific training, reinforcing both security and accountability.

Confident close-out and TMF transfer

Before study close-out, a final completeness and quality review is conducted, ensuring all findings are resolved prior to TMF transfer. Sponsors receive a TMF that is complete, compliant, and inspection-read, meeting both regulatory and archival expectations.