Adapted from a Phlexglobal Ask An Expert interactive discussion, “How to Ensure TMF Inspection Readiness & Compliance for a Recently Acquired Product,” held March 2, 2022 and available on-demand here. Second in a series; you can read the first blog - “Why Is the Trial Master File Critical in M&A activities?” – here, and the third blog, "How Quality Review and Heatmaps Can Reduce Remediation Time, Cost, and Effort for an Acquired Trial Master File" here.
In an industry filled with mergers and acquisitions (M&As), obtaining responsibility for an existing Trial Master File (TMF) is not uncommon. It can be extremely challenging to transition responsibility smoothly, however, particularly with an active TMF or one from an older study.
Following are common issues Phlexglobal’s TMF experts encounter with an acquired Trial Master File:
- No workable index
- Missing, inconsistent, and corrupted content
- Mix of paper and electronic documents
- Multiple file formats for the electronic files, such as PDFs, ZIP files, and annotation attachments
- Incomplete audit logs
- Key essential documents in local languages that have not been translated
Thoughtful planning while considering what regulatory authorities will want to see in your TMF will help to reduce issues and ensure inspection-readiness of the Trial Master File for an acquired product or study.
Accessing the TMF
It is very important to get access to the TMF as early as possible in an M&A scenario. This will allow you to assess the content, identify gaps or other issues, and develop your strategy for maintaining and documenting compliance. Often, access to knowledgeable resources is contractually limited to a specific timeframe so it’s important to act quickly.
By accessing your newly acquired TMF, you can begin the process of assessing past practices, addressing current state issues, and formulating your plans for the future. This holistic approach allows a greater understanding of the lifecycle of the TMF and the clinical trial it supports.
For an electronic trial master file (eTMF), in addition to content, you will also want to access the audit trails of the legacy system. These will provide important context for how the TMF was managed and controlled over time and should be available if an inspector requests access. You can also determine if the TMF Reference Model was used within the system to manage and track content, since that will make data mapping and migration easier. If the Model wasn’t used, you can adapt your assessment and any migration plans accordingly.
TMF Quality and Completeness
Assessing the content and the overall state of the eTMF’s quality and completeness may require deeper analysis. We recommend a detailed TMF quality review (sometimes called a “file review”), which provides a line-by-line evaluation of your TMF, giving you detailed insight into its quality, completeness, and timeliness. Combined with advanced tools such as heatmaps and analysis by expert TMF practitioners, these visual and textual roadmaps highlight and prioritize missing documents and other issues that warrant further action – letting you make even the most challenging TMF “black box” inspection-ready.
Is There a TMF Plan?
The TMF plan is a critical component of the Trial Master File, and your inspection-ready TMF for an acquired product or study will require one. Check to see if it already exists – if it does, review it to ensure that it meets core requirements (you can access a TMF plan template here that was created by the TMF Plan Template Subgroup of the TMF Reference Model Project). If there isn’t a TMF plan, you will need to create one retrospectively, which can involve a tremendous amount of time and effort depending on the state of the TMF.
Why is the TMF plan so important? It’s where you document the state of the TMF content and rationalize your approach to addressing issues. It includes the TMF format, structure, and specifications and describes how you will manage the TMF moving forward, including any risk mitigation efforts.
The TMF plan also describes how trial records will be managed during and after the trial and includes eventual archiving and destruction policies. It also describes key roles that may be held by internal resources or external partners such as a Contract Research Organization (CRO). Information from a quality review and/or heatmap exercise will further inform and improve the TMF plan.
Need help or have questions about an acquired a Trial Master File? Request a complimentary assessment from one of our TMF experts today.