a specification and an example XML exchange file for an eTMF Exchange Mechanism Standard at the DIA Global Meeting in Boston, USA. Use of this standard will help facilitate the exchange of TMF content between systems. TMF recent developments In February 2013, the EMA (European Medicines Agency) created a draft guideline document that recognizes the importance and legal equivalence of the TMF and the eTMF, and provided guidance to organizations implementing TMFs and eTMF systems. In the guideline document, EMA inspectors state that paper TMF documents may be stored in electronic eTMF systems, and after this process, that the paper may be destroyed. The use of eTMF systems for electronic storage is fully supported by the EMA in clinical trials as a replacement for paper. In a cautionary statement, the agency cites quality problems with TMFs and eTMFs due to document quality and discrepancies such as missing pages, improper labelling or missing documents.[16] In April 2014, the European Parliament approved Regulation (EU) No 536/2014 on clinical trials on medicinal products for human use, repealing Directive 2001/20/EC.[17] Article 57 of the Regulation requires that the TMF "shall at all times contain the essential documents relating to that clinical trial which allow verification of the conduct of a clinical trial and the quality of the data generated", confirming that the trial master file should be maintained contemporaneously. Article 58 requires that "the sponsor and investigator shall archive the content of the clinical trial master file for at least 25 years after the end of the clinical trial." This requirement defines a minimum retention period across the EU for all clinical trial master files, irrespective of whether the data subsequently supports a marketing authorization approval. Companies Many contract research organizations (CROs) provide document management services to support trial master file management. In addition, there are a small number of niche companies that focus specifically on the trial master file. Their services include process and quality consultancy, management and filing of trial master file content and provision of trial master file document management technology solutions (eTMFs). References 1. TMF Reference Model 2. EU Parliament Directive 2005/28/EC 63 Chapter 4 3. US FDA Guidance for Industry 4. TMF Reference Model 2.0 5. European Medicines Agency, 9. Problems found with Trial Master Files from GCP inspections, Jan 2013 6. European EC Regulations Clinical trials