Is your eTMF Ready for an Audit?

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Applied Clinical Trials

Electronic Trial Master Files (eTMFs) are growing in popularity.  A recent industry coalition survey summarized by eClinica reported that in 2012, 32% of survey respondents maintain inspectable TMF’s in paper only, down from 50% in the corresponding 2010 survey. While there is only a modest increase in the number of respondents maintaining inspectable electronic TMFs (8%), the increase in the number of respondents maintaining a combination of paper and electronic was significant – 48% in 2012, compared to just 27% in 2010, indicating a continuing transition to eTMF in the industry.

As with most innovations, the benefits gained with eTMF also require new ways of working.  One of the most important considerations for companies maintaining eTMFs or hybrid paper/eTMFs is how to handle agency audits.  When paper TMFs are audited, the sponsor, CRO or investigator must ensure that all of the paper records are available, and assist the auditor in accessing them and locating information.  Usually, all of the parties involved have many years’ experience in assessing the quality and completeness of the paper TMF.

With an eTMF, an inspector has new concerns:

  • Was a validated QC process used when paper documents were scanned and uploaded into the TMF to ensure that the final records were accurate, complete and legible? 
  • Does the system maintain records to prove that this process was followed?

  • Have all documents in a completed study completed the defined QC process?

  • Has justification been provided for expected documents that were not received?

  • Are records in the eTMF secured against unauthorized access or alteration?

  • Are all significant actions recorded in an audit trail that can be understood by users and auditors?

  • Are associated paper records preserved and retrievable unless a certified process has been put in place for their destruction?  (see the recent position paper Framework for the Destruction of Paper)

  • Are records retention policies documented and followed?

  • Can the full TMF be provided including both electronic documents and those retained only in paper? 

  • Can the inspectors access all electronic documents relevant to the inspected site or sites directly, using a user-friendly interface with reasonable performance?  Are the records indexed in a manner that makes it clear that all essential documents have been collected?

  • Can the validation records for the system be provided?

    If these requirements were considered when the eTMF was designed and implemented, ensuring the audit-readiness of a specific TMF should be straightforward. Compliant processes for scanning upload, and QC should be standard, not optional. Queries and reports should provide a catalog of the documents comprising the TMF, revealing any missing documents or documents that have not completed the QC process.

    Although eTMFs are new, authorities are beginning to signal their willingness to – and even preference for – conducting TMF audits in an eTMF environment.  (For comments on eTMF from a MHRA inspector, see the DIA presentation GCP Inspection of Trial Master Files.)  They expect sponsors to take the steps needed to provide them with the tools and information needed to conduct quality audits in a timely manner.