Tracking TMF Timeliness

The success of a clinical trial relies heavily on maintaining an organized and complete Trial Master File (TMF). Adherence to timely filing requirements helps to ensure the accuracy, completeness, and audit readiness of the TMF. Regulatory agencies, including the International Conference on Harmonisation (ICH), the US Food and Drug Administration (FDA), and the European Medicines Agency (EMA), require that TMF documents be filed in a timely and accurate manner, and as soon as possible after they are created, reviewed, and approved. The Medicines and Healthcare products Regulatory Agency (MHRA) in the UK has stated that documentation in the TMF that is relied upon for subsequent activities should be filed in the TMF before those activities take place. For example, monitoring visits rely on the information in the previous report, so the previous report should be completed and filed in the TMF before the next visit. This guidance suggests that the filing of TMF documents should be timely to ensure that subsequent activities are not delayed. However, regulatory authorities generally do not provide specific guidance on TMF filing timelines.

So what time frame is considered “Timely”? and how do we measure it? Industrywide, there is a general consensus that documents should be filed within 30 days. However, there are differences in opinion on the appropriate measurement date to “file within 30 days” of. Some organizations commonly use the Document Receipt Date to the Document Upload Date as a measure of TMF filing. However, this method can be manipulated by a user to create the impression of timely filing. Alternatively, some organizations use the Document Date to Finalization Date to measure TMF filing, which does not work well with documents that were not prepared specifically for the trial, such as a CV that was finalized a year ago but just uploaded.

In any measurement, applicability is key. One good option to ensure that your metric is providing accurate and helpful information is to define a “TMf Ready” date that allows for adjustment according to your organization’s practices. For example, “TMF Ready” can be defined as “ For documents created internally, the TMF Ready date is the Finalization/Last Signature Date, for documents gathered externally the TMF Ready Date is the Receipt Date”. The definition your organization chooses can vary depending on a multitude of factors, CROs and other Vendors often have their own SOPs to adhere to so conversations during vendor selection and clear written instruction is vital to ensuring compliance. The effort is worth it, and a TMF that is filed contemporaneously is enormously beneficial when it comes time for audits or inspections.