16 - 19 September, 2019 | Pullman Brussels Centre Midi Hotel, Brussels, Belgium

Avoid Critical Findings in your TMF

By: Andrew Robertson

We have put together some of the most common critical findings related to TMF management in GCP inspections, these findings demonstrate the importance of robust information management, careful document presentation and highly organised data filing in maintaining an inspection ready TMF.

CRITICAL FINDING - TMF did not contain all the essential documents

“The TMF was presented as a paper TMF for inspection. However, the TMF did not contain all the essential documents required to enable the reconstruction of trial events and demonstrate compliance with the regulations and the organisation’s own quality system. Several essential documents were retained within different electronic systems which were not defined to be part of the TMF and to which inspectors were not provided direct access (even with a guide user). The TMF had not been fully defined to include all the ancillary systems and the documents located within them.”

Don't be caught out during your TMF - eTMF transition! This critical finding highlights how unpredictable inspections can be, just because you have all the documents in paper or electronic form doesn't necessarily mean you are compliant.

CRITICAL FINDING - Documents were not filed consistently or correctly

“The inspector requested documents that could not be located in the eTMF. Despite the assistance of the study team and the eTMF experts, not all these documents could be found over the 4-day inspection, and those that were provided took two days to locate. Documents were not filed consistently or correctly with documents at the inappropriate level of the TMF (e.g. Product Level vs Study Level.) There were many documents missing from the eTMF, for example, signature sheets, correspondence, emails and previous versions of documents.”

This critical finding highlights the importance of establishing a reliable filing system for all your TMF/eTMF documents. Even if you do possess all the correct documentation, inconsistencies in filing could mean the inspector is unable to locate certain documents.

CRITICAL FINDING - The eTMF was incomplete and unreliable

“The eTMF was incomplete and unreliable with emails incomplete, duplicate documents, blank/incomplete documents, the same name for many different documents, same document under different names and in different locations and missing documents. The eTMF management SOP required that there be monthly QC of all eTMFs at a study level, but this was not occurring. The audit trails for all 5 eTMFs reviewed during the inspection showed there was a large number of documents uploaded following the inspection notice prior to the inspection showing the eTMFs were not being updated regularly and therefore were not being kept in an inspection ready state.”

TMF and Inspection Readiness needs to be continually worked on throughout your entire process - a well thought out strategy and small amount of time spent on filing properly would have avoided this critical finding.

CRITICAL FINDING - The CROs TMF did not meet the requirements

"The Trial Master File (TMF) presented for inspection did not meet the requirements of the legislation for it being the basis of the inspection, readily available, directly accessible and complete, to the extent that the TMF impeded inspectors from assessing GCP and legislative compliance. The inspection was extended as it required the Inspectors to return after four months to enable review of clinical trial compliance. In the interim period, the CRO were required to undertake significant work to ensure the three selected TMFs were complete for inspection."


The CRO must clearly define and communicate with the Sponsor the scope of the TMF that is required to be held by the CRO. The TMF must be maintained to a sufficient standard by all parties and be consistently accurate

People also read: Implementing a Robust eTMF System – What to Consider - read here

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