If It’s Not Documented, It Didn’t Happen – Importance of The Trial Master File

Posted in Process Improvement

The Trial Master File (TMF/eTMF) is essential in telling the story of how your organization conducted your clinical trial activities, including how you ensured data integrity, patient safety, and compliance throughout the conduct of your trial. The TMF is a critical component of the trial process and is typically a primary area of focus for a regulatory inspector during an inspection.

We all know that “If it’s not documented, it didn’t happen,” and we can take that a step further when considering your TMF. If a document is not filed appropriately, it can be considered not done during an inspection. An inspector will not likely go hunting for it and your organization may not be given the opportunity to locate it either.

All regulatory bodies focus on the TMF during an inspection but there is special emphasis given by MHRA, as the basis of their inspection is the TMF.

WCG Avoca has collected information regarding critical and major findings by MHRA for the years April 2018 – April 2019 (2018-2019) and April 2017 – April 2018 (2017-2018) and found that 15% or more of the major findings were in the following categories:

  • Pharmacovigilance
  • Record Keeping and Essential Documents/TMF

The importance of the TMF cannot be understated.

It is always best to build out a quality TMF/eTMF from the onset, but it is equally important to consistently conduct reviews of your TMF. Reviewing your TMF is an essential part of proactively ensuring an on-going state of inspection readiness. In addition, your organization should be implementing ALCOA-C principles for clinical trial documentation which require that the Trial Master File be attributable, legible, contemporaneous, original, accurate, and complete.

At the end of the day there is a person behind the documents, and you are telling the story of how your organization ensured that person’s safety and the integrity of the data they helped provide.

In our industry we must always be inspection ready but make no mistake, if your TMF isn’t inspection ready then neither is your organization. Failure to make your TMF a top priority can lead to delays in clinical trial completion, it can add unnecessary stress to personnel during an inspection, and ultimately it could impede your organization from bringing your drug to market.

The FDA recently stated that the COVID-19 pandemic resulted in the need to be flexible and evolve, but “the importance of protecting patients and adequate documentation remain mission critical to the agency.”

So, what do you do if you know or suspect that your TMF might need some attention? When is the last time you conducted a periodic review of your TMF?

Periodic reviews should be documented and include information on any identified deficiencies along with how and when those deficiencies were addressed. 

Areas of focus for your TMF review generally include the following:

  • ICH E6 Essential Documents
  • Organization and Personnel
  • Quality Management
  • External Service Provider
  • IT Systems
  • Clinical Study Management
  • Investigator Sites
  • Monitoring
  • Pharmacovigilance
  • Regulatory Affairs
  • IMP Management
  • Labs
  • Biostatistics
  • Data Management 

Once you know where the issues lie within your TMF/eTMF, you can get to work on addressing the gaps.

In alignment with Regulatory Agency recommendations for having a complete, correct, current, and accessible TMF for Inspection Readiness, WCG Avoca has developed an Inspection Readiness Dashboard. The dashboard allows users to capture inspection activities at various timepoints, specify relative risk levels, and indicate the status of ICH E6 essential documents (e.g., complete, filed, missing). WCG Avoca Quality Consortium (AQC) Members can access the Inspection Readiness Dashboard in the Knowledge Center.

This is just one of many risk-based tools available to AQC Members in our Knowledge Center, which consists of over 1,000 regulatory compliant leading practice tools and templates customizable to their organization to be inspection ready. View the current catalog of tools.

In addition to the tools available to assist with inspection readiness, WCG Avoca has consulting services which can conduct periodic TMF reviews for you while completing the Inspection Readiness grid in order to understand your current state of inspection preparedness.

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Learn more about AQC Member benefits or consulting services for your organization to ensure your TMF is inspection-ready.
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