How to Ensure a Successful TMF Remediation

October 27, 2015

  • eTMF Resources

Performing an accurate and timely quality review of the Trial Master File (TMF) is key to ensure inspection readiness at all times.  While performing the QC, the reviewers may come across discrepancies that require remediation.  Remediation may include (not an exhaustive list) obtaining a document from a site, obtaining a missing signature, or filing a new version of a document. Without the right process in place, remediation of the TMF can be an expensive and time consuming process.

According to Sholeh Ehdaivand, President and Chief Executive Officer of LMK Clinical Research, the most important factor in successful TMF remediation is ensuring due diligence is performed in a timely manner.

“Organizations that follow strict procedures to ensure they regularly conduct QC and address discrepancies immediately upon discovery are more likely to resolve this issues thereby ensuring an accurate, inspection-ready TMF,” Ehdaivand said.

In order to help organizations improve their remediation process, Ehdaivand outlined three steps to ensure a successful TMF remediation.

Three Steps to a Successful TMF Remediation

    1. Regularly perform QC, and address discrepancies in a timely manner. The longer you wait, the harder it is to successfully remediate the problem.Example: Three submissions have been made to a regulatory agency, but only two responses are present in the TMF. A QC professional is searching for the other response. He contacts the document owner of the third submission to alert her of the missing document. The document owner discovers that the response was faxed to her when she was on vacation. The regulatory response is still sitting on her fax machine. In minutes, the document owner files the document into the TMF, completing the remediation process for Submission 3.

      “Here we see the importance of timeliness,” said Ehdaivand. “If the QC professional had waited any longer to contact the document owner, the faxed response could have easily ended up lost or in the recycling bin.”

2. Know what requires remediation. Ensure that you have QC experts in place who know what documents are needed for an accurate and complete TMF.

Example: A novice QC professional conducts remediation on the fourth regulatory submission. It was sent to the regulatory agency months ago, but does not have a response in the TMF. The QC professional marks it as an incomplete document in  the TMF and contacts the document owner. The document owner explains that the regulatory agency does not provide a response for that type of submission. A response letter should not be expected, therefore it was never missing.

“In this scenario, we see the importance of having a fully-trained and experienced QC team,” Ehdaivand said. “A QC expert would know that Submission 4 never required a response and would not have contacted the document owner requesting a response and wasting valuable time.”

3. Maintain consistent processes and standards throughout your documentation and QC process.

Example:Your organization collects paper documents and scans them into your eTMF. Two people perform QC on these documents. Do they both understand the criteria for activating a document within TMF? Both people need to have the same standards for indicating that a document is legible. Otherwise, you could access a set of documents after the study is closed and discover that some are unreadable. At that point, you would be stuck with the illegible documents.

“As the final check point for your eTMF documents, it is crucial to maintain consistent standards for pass/fail within your QC team,” Ehdaivand said. “Identify these standards at the beginning of your trial, and set training and procedures in place to ensure they are maintained throughout the entire trial.”