US. The EU Commission's Directive 2005/28/EC 63 Chapter 4 states 'the trial master file shall consist of essential documents, which enable both the conduct of a clinical trial and the quality of the data produced to be evaluated. Those documents shall show whether the investigator and the sponsor have complied with the principles and guidelines of good clinical practice and with the applicable requirements.' The US FDA recognizes the use of TMFs as a significant piece of information but unlike the EU with its TMF regulation, there is no formal requirement for maintenance of essential documents in a TMF in US-based clinical trials in the U.S. Code of Federal Regulations. However, since the U.S. FDA require trials to be conducted in compliance with ICH GCP, there is an expectation that a trial master file will be created and maintained in accordance with those guidelines. TMF content The United States, the EU and Japan support the International Conference on Harmonisation or ICH. The ICH has published a minimum set of essential documents for the TMF. The minimum essential documents that are required for the registration of pharmaceutical products designed for human use are specified in the document 'ICH Good Clinical Practices,' published in 1997 by the ICH Example ICH essential documents that would be required in any US, EU or Japan based clinical trial would include: signed protocol, audit certificate, subject enrollment log. Although the ICH guidelines are applicable to the three named ICH regions, many other countries have agreed to follow the guidelines and have incorporated the principles into their national medicines legislation. Creation of a TMF and inclusion of ICH essential documents is based on the discretion of the regulatory agency for the country in which the clinical trial is conducted. In addition, the submission of a marketing application will normally require compliance with the regulatory requirements of that country, including requirements specific to TMF content. TMF content classification efforts Since the requirement to maintain a TMF containing essential records was documented in the ICH GCP E6 Consolidated Guideline in 1996, trial sponsors have struggled to identify exactly what content the TMF should contain. ICH E6 includes details of only a minimum list of contents and no other regulation or guideline provides a comprehensive list of TMF content. As a result of the inconsistencies that were developing across the sector, an industry group comprising about 20 members from the