LMK’s Oversight TMF QC Process Ensures TMF Completeness


A small biotech company outsourced the data management, monitoring, and regulatory functions of their oncology program to a clinical research organization (CRO). Unfortunately, the biotech company did not have a process in place to perform oversight of the Trial Master File (TMF) throughout the duration of the study. The sponsor contracted LMK to provide Oversight Quality Control (QC) of the TMF and resources to perform QC of the documentation collected and stored by the CRO.

LMK Solutions:

LMK’s team took the following steps to ensure TMF completeness:

  1. Reviewed the CRO’s and client’s TMF SOPs and the TMF Plan for the program, which the CRO developed and the biotech company approved, to better understand the overall TMF process being used and the TMF Master Table of Contents.
  2. Created a list of Essential Documents based on ICH Essential Documents List, the SOPs, and the TMF Plan after understanding the Plan. The sponsor did not implement the TMF Reference Model for their program.
  3. Mapped the documents to the study timeline and estimated at which time points the documents should be present based on the document list.
  4. Created an Oversight Checklist based on the documents and timelines provided by the Functional Line of the biotech team. The biotech team performed their oversight review quarterly and provided continuous feedback to the CRO ensuring an inspection-ready TMF throughout the life of the program.


The biotech company added another way to perform oversight of their CRO by reviewing the foundation of the clinical trials—the TMF. The Oversight QC revealed gaps in documentation collection times and document quality. As a result of the QC and per LMK’s recommendation, the sponsor and the CRO added the “TMF” to their weekly team meetings and created an Oversight QC schedule. The schedule included a remediation timeframe for the CRO to address discrepancies. The checklist was the documented proof that the oversight occurred, and the list provided clear documentation of which documents were present and which were missing.