EUnetHTA (European Network for Health Technology Assessment) Joint Action 3 (JA3) is a collaborative network project consisting of 83 organisations from 30 European countries. One of the main objectives is to lay the foundation for a sustainable model of European collaboration on Health technology Assessment (HTA). A central part of this is the establishment of a quality management system (QMS) for the production of high-quality HTA-reports. Since the start of JA3 in May 2016, 27 partner organisations from different European countries and regions have been jointly developing, elaborating and maintaining around 40 standard operating procedures (SOPs) and other parts of the QMS. Previously developed methodological guidelines, templates and tools have undergone required updates; two new guidelines are currently in production. Thereby, this collaboration of a broad variety of partners has offered opportunities and entailed challenges. The wide heterogeneity of given regional and national health care systems throughout the continent with different conditions for reimbursement, HTA-procedures and resource endowments remarkably influence how processes and methods, which are designed for the European context, are understood and formulated. Examples include the data requirements and the mode of stakeholder involvement. To overcome these barriers, remedies have been created such as an information specialist network, a consensus procedure in case of unresolvable disagreements and trainings on practical aspects. The work results benefited from the exchange of different views and from a broad spectrum of experiences and expertise. The concentrated scientific and practical knowledge is one of the major virtues of European consortium projects. The piloting and continuous evaluation of the established QMS helps to improve the mode of collaboration by identifying gaps and shortcomings of the newly developed processes, methods and products. However, to find a balance between adequate processes and given restrictions of national settings will be an ongoing task.