title: Quality expectations and tolerance limits of trial master files (TMF) - Developing a risk-based approach for quality assessments of TMFs.
abstract: This article addresses the question of when a trial master file (TMF) can be considered sufficiently accurate and complete: What attributes does the TMF need to have so that a clinical trial can be adequately reconstructed from documented data and procedures? Clinical trial sponsors face significant challenges in assembling the TMF, especially when dealing with large, international, multicenter studies; despite all newly introduced archiving techniques it is becoming more and more difficult to ensure that the TMF is complete. This is directly reflected in the number of inspection findings reported and published by the EMA in 2014. Based on quality risk management principles in clinical trials the authors defined the quality expectations for the different document types in a TMF and furthermore defined tolerance limits for missing documents. This publication provides guidance on what type of documents and processes are most important, and in consequence, indicates on which documents and processes trial team staff should focus in order to achieve a high-quality TMF. The members of this working group belong to the CQAG Group (Clinical Quality Assurance Germany) and are QA (quality assurance) experts (auditors or compliance functions) with long-term experience in the practical handling of TMFs.
authors.affiliation: Global Quality Medicine, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: Arthur
authors.initials: A
authors.lastname: Hecht
authors.affiliation: Quality Medicine Germany, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Busch-Heidger
authors.affiliation: R&D Clinical & Medical Quality Operations, Sanofi, Chilly-Mazarin, France.
authors.forename: Heiner
authors.initials: H
authors.lastname: Gertzen
authors.affiliation: Quality Medicine Germany, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany.
authors.forename: Heike
authors.initials: H
authors.lastname: Pfister
authors.affiliation: Clinical Project Management Specialty Medicine, Bayer Pharma AG, Berlin, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Ruhfus
authors.affiliation: Global Inspection Management, Merck Serono, Darmstadt, Germany.
authors.forename: Per-Holger
authors.initials: PH
authors.lastname: Sanden
authors.affiliation: Global Clinical Trial Operations, MSD SHARP & DOHME GMBH, München, Germany.
authors.forename: Gabriele B
authors.initials: GB
authors.lastname: Schmidt
mesh_terms: D002986:Clinical Trials as Topic / Q000379:methods*; D000068598:Data Accuracy; D066289:Data Curation; D005371:Filing / Q000379:methods / Q000592:standards; D017408:Guidelines as Topic; D006801:Humans; D058996:Quality Improvement / Q000458:organization & administration; D011996:Records / Q000592:standards*; D012308:Risk Management / Q000458:organization & administration*
keywords: clinical trial; quality risk management; trial master file