How to Create and Maintain
a TMF Inspection-Ready Culture

This is part one in a series of checklists to create and maintain an inspection-ready culture and prepare for a regulatory inspection.

Preparing for a regulatory inspection can be daunting — but it doesn’t have to be. The best approach to reduce the stress of an inspection is to create a culture of compliance by building inspection-readiness practices into daily operations.

Inspection readiness begins and ends with your TMF. Below are nine tips to help you achieve an inspection-ready TMF at all times, sustain a culture of compliance in your organization, and make TMF a strategic asset within your organization.

• Gain executive buy-in and support

  Leadership endorsement is essential to build and maintain an inspection-ready culture. Ongoing and consistent communication from executives is critical in making sure that everyone is aware of the benefits of incorporating inspection-readiness practices into daily operations. One top 20 pharma also named a senior executive in their SOP, which helped indicate the significance of TMF to the rest of the organization.

• Involve and get feedback from study teams

  Make it a practice to gather feedback from internal and external study teams, including sponsors, CROs, and/or sites. This can be done during study planning, training sessions, or pre-defined times throughout the study. One emerging biopharma conducts annual surveys with end users to establish a benchmark and identify ways to improve processes for those users.

  Involving all stakeholders regularly in the process will increase trust, improve collaboration, and maintain high-quality documentation practices throughout the study.

• Take appropriate care when creating your TMF plan and index

  A well-developed TMF plan includes the roles and responsibilities of internal and external partners across the study, document content requirements, instructions for inspections, and the type and frequency of quality checks. One emerging biopharma has their TMF plan serve like a contract for all TMF contributors — both internal and external — and set forth TMF expectations and metrics at the study level. Some sponsors partner with CROs to define study-level plans and ensure alignment.

  The TMF plan is a living document that should be reviewed and updated on a regular basis to ensure the TMF is fully leveraged to enable a constant state of inspection readiness for your organization. An excellent TMF plan template can be downloaded from the TMF Reference Model website.

  The TMF index supplements the TMF plan by confirming the location of each study document type during the course of the study. Where study-related documents may be stored in alternate locations to support operations, the TMF index shows that there is clear understanding of where the source of truth is.

• Actively manage your TMF to keep it up-to-date at all times

  An active TMF operating model ensures a constant state of inspection readiness by managing all TMF documents, related information, and processes in the same system, in real-time, as they are executed.

  Incorporate active TMF management practices into daily operations by submitting all TMF documents in a timely and contemporaneous manner. Apply risk-based quality control checks to ensure they are accurate and complete. Each action should be traceable and auditable for inspectors to review.

  One emerging biopharma passed an FDA inspection with only two days’ notice by creating a culture of quality and inspection readiness. They took steps to integrate the eTMF in their business process, including: engaging document owners with an accountability matrix that outlined roles and associated expectations, using reports and dashboards to assess TMF health throughout the study lifecycle, and training and re-training employees as needed.

• Train (and retrain) employees on how to stay compliant

  Training should include regulations, the company’s processes, and information about the construct of the TMF, such as how documents are to be filed and TMF user roles and responsibilities. All new team members should receive this training as part of their onboarding process. Review training materials regularly, revise as needed, and retrain all current team members when changes occur.

  In addition to formalized training, one top 20 pharma views ongoing education as an important component of engaging both senior leadership and end users by sharing the value of TMF.

• Leverage governance and oversight processes to ensure compliance

  Good Clinical Practice (GCP) requires that the sponsor demonstrate ongoing oversight throughout the trial for studies conducted in-house and those outsourced to vendors. Clearly define your oversight activities, detail how performance will be measured, and provide evidence-based documentation within your TMF.

  One top 20 biopharma’s CROs work in the sponsor eTMF, and those CROs follow their own TMF management SOPs. The biopharma also created a robust guidance document to bridge the gaps between the CRO and their own SOPs, improve consistency, and clearly communicate expectations. The biopharma then uses reports and dashboards for periodic TMF quality reviews.

• Use reports and KPIs to maintain compliance

  Organizations can use operational metrics and key performance indicators (KPIs) to increase visibility into TMF status. Establish and monitor KPIs to drive inspection readiness and inform proactive decision-making.

  Design reports to help identify issues before they become problems, and use KPIs to assess TMF timeliness, accuracy, and completeness. Checking these on a regularly scheduled basis will enable your organization to identify and resolve TMF issues proactively, before an inspection occurs.

  One emerging biopharma creates quarterly report cards that provide a study-level snapshot of key metrics for their CROs. If metrics on that report card fall below a defined threshold, they trigger a “get well” plan, such as retraining or conducting a site visit for document collection.

• Conduct regular QA audits and/or periodic mock inspections

  Just as a fire drill helps everyone in a building prepare for an emergency, conducting internal audits and mock inspections ensures your organization is ready for an inspection. Leverage these activities to identify areas where processes and/or performance can be enhanced or improved.

  Practice answering questions succinctly about who is responsible for each step in the document collection and filing process, and how security and roles are handled. This should ensure that no process has a step without a follow-up, and that there is a record or audit trail to support each step. The team should also be able to discuss how the eTMF is set up and how computer systems validation supports its use.

• Plan for change

  Be prepared to modify your TMF and TMF plan to accommodate any necessary regulatory changes in a timely manner. It is better to incorporate changes when needed rather than risk citation for failure to comply during an inspection.

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  RELATED READING

  • Part 1: Build Compliance Culture
  • Part 2: Prepare for Inspection
  • Part 3: Navigate Inspection Day
  • 2024 TMF Trend Report

  This is part one in a series of checklists to create and maintain an inspection-ready culture and prepare for a regulatory inspection.

  Read the next checklist to learn what key sections to include in your SOP and other tips to prepare for an inspection.