TMF Risk-Based Quality Control: What Does This Really Mean?

By Eldin Rammell

Trial Master File (TMF) quality control is a topic that always seems to be present on conference agendas and it invokes much discussion and debate. Many clinical trial sponsors and contract research organizations (CROs) are struggling to understand what is needed in terms of quality control and quality review activities and how these can be done more efficiently to improve TMF health and inspection-readiness.

According to ICH E6(R2), quality control is “the operational techniques and activities undertaken within the quality assurance system to verify that the requirements for quality of the trial-related activities have been fulfilled.” This means that to perform overall quality control (QC) we need to embed activities as a) part of a quality assurance system – in other words, under a pre-defined and documented regime – and b) according to specific requirements – that is, with an understanding of the quality level that is required. These QC activities must also include a verification step – Quality Review. This step checks that the quality is acceptable and is an aspect of quality control that is most misunderstood. If Quality Review is performed in an ad hoc manner, then it is not part of a pre-defined regime. Similarly, if individuals have the flexibility to define their own quality activities then it is also unlikely to be done according to specific requirements.

So, how can we best meet these two requirements for effective quality control in a Trial Master File?