Uncovering efficiencies in clinical drug trials related to the trial master file

by William Hamilton and Gireesh Gaonkar

How best to manage the trial master file is a subject of much debate for pharmaceutical companies. Is an electronic trial master file (eTMF) necessarily the right approach? Who are the stakeholders involved in managing the trial master file? And how do you ensure clear lines of accountability with the TMF and associated processes? These were some of the questions raised during the 7th European Trial Master File Summit held in London in October.

Keynote speaker Andy Fisher, lead senior Good Clinical Practice (GCP) inspector at the Medicines and Healthcare products Regulatory Agency (MHRA), spent time with attendees on the last day of the conference to answer these and other questions. The approach companies take to manage their TMF and the processes and solutions they use can vary significantly, but Mr. Fisher emphasized that it isn’t significant how different or similar each company’s processes are; what matters is that the process is well-defined and well-documented, that inspectors can find the information they need and verify the quality and validity of the trial.

One of the most prominent messages during the various discussions centered around the TMF Reference Model. While there is no requirement to adopt the Reference Model, it does improve productivity and efficiency because it establishes standards based on the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) vocabulary, ICH regulatory requirements, and broadly accepted principles for TMF management. There is no set way to adopt the Reference Model, and it can be adapted for paper or electronic use. Some companies use it out of the box, some include their own modifications, and others have their own homegrown reference models.

Whatever the approach, the emphasis needs to be on communication of the TMF process. During an inspection, what authorities will be looking for is documentation of your processes. So, regardless of when and how documents are sent from clinical sites, how quickly problems are resolved, or whether you have variations from the TMF reference model, what the inspectors care about is that steps are documented, that the process is consistent, and that everyone follows the same procedure. And how successfully those steps and that documentation are managed comes down to communication.

Developing relevant metrics

Besides clear, verifiable processes and the role the TMF Reference Model plays in improving efficiency, another important discussion focused on metrics for the TMF process. During her presentation, Gergana Koutsarova, global TMF process owner at AstraZeneca, discussed the fact that metrics can mean many things to many people, and that the information gathered from the metrics depends on who is involved, including sponsors, contract research organizations (CROs), someone from the process side, someone from clinical or someone from IT.

The information each stakeholder is looking for will vary depending on its role. For example, if the system isn’t performing and it takes 24 hours to upload a document, the metrics need to make those issues clear to IT. What matters is that the metrics are relevant to the particular stakeholder or the importance of the message will be lost.

Let’s get back to that question about paper vs. electronic. Discussions during the summit made it clear that organizations shouldn’t feel pressured to implement electronic processes if they have efficient paper processes; nor should it be assumed that using electronic processes will automatically lead to improvements. Indeed, as) pointed out in an earlier blog, even companies that have partially or completely adopted electronic TMF processes often still struggle with inefficiencies and inconsistencies. However, an eTMF approach does confer certain benefits and can promote better communication among different members of the trial team.

One last takeaway from the European Trial Master File Summit is that there is no sense of proprietary information when it comes to TMF processes. Experts in the TMF space from all organizations — companies large and small, technology vendors and CROs — are eager to collaborate and share best practices on managing the TMF process.

TMF processes can be simplified and made more efficient, and the first step toward better processes is clear communication. We look forward to sharing our knowledge and experience of best practices with clients.

William Hamilton is a senior product integrator with over twenty years of experience in the life sciences industry. He has been involved with custom and enterprise content management systems for multiple verticals exclusively for the pharmaceutical industry.  Working primarily in a technical capacity, he has participated in all phases of software development such as application design and development, testing, delivery, requirement gathering, and end user training.



Gireesh Gaonkar is the account general manager for DXC Life Sciences in the United Kingdom and Ireland. He is an advocate and keen proponent of the convergence of pharma with payers and providers in the health outcomes marketplace. He has over 20 years of experience in the life sciences industry.

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