Regulation (EU) 2017/746 (IVDR): practical implementation of annex I in pathology

Abstract

Background: Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR) imposes several conditions on pathology departments that develop and use in-house in vitro diagnostic medical devices (IH-IVDs). However, not all of these conditions need to be implemented immediately after the IVDR entered into force on 26 May 2022. Based on an amending regulation of the European Parliament and the Council of the European Union, the requirements for IH-IVDs will be phased in. Conformity with the essential safety and performance requirements of annex I must be ensured from May 2022.

Objectives: With this article, we would like to present the practical implementation of the currently valid conditions for IH-IVDs at the Institute of Pathology at the University Hospital of Heidelberg, in order to provide possible assistance to other institutions.

Conclusions: In addition to the intensive work on the requirements for IH-IVDs, several guidance documents and handouts provide orientation for the implementation and harmonisation of the requirements for healthcare institutions mentioned in Article 5 (5). Exchange in academic network structures is also of great importance for the interpretation and practical implementation of the IVDR. For university and nonuniversity institutions, ensuring conformity with the IVDR represents a further challenge in terms of personnel and time, in addition to the essential tasks of patient care, teaching and research and the further development of methods for optimal and targeted diagnostics, as well as the maintenance of the constantly evolving quality management system.

Keywords: In-house manufacturing; Laboratory-developed tests; Quality Assurance in health care; Quality Management; Regulatory requirements.

Fig. 1

Currently applicable conditions for in-house in vitro diagnostic medical devices (IH-IVD) according to Regulation 2017/746 (IVDR), Article 5 (5). For conditions (b)–(i), a later start date was decided [16]

Fig. 2

Annex I is subdivided into three chapters. Chapter I addresses the establishment of risk management. Chapter II contains the performance record as a central topic. Chapter III contains requirements for the labelling and instructions for use of IVDs. The basis of all chapters and requirements is the intended purpose and the associated risk classification. The intended purpose of the IH-IVD influences the effort required to implement the three central elements

Fig. 3

Formulation of the intended purpose for in-house in vitro diagnostic medical devices (IH-IVD). Several components (blue) are included and defined (green) as part of the determination of the intended purpose. The documentation is device specific, e.g., in the form of a checklist on a standard form

Fig. 4

Device-specific risk management. a Risk management file: documentation of the risk management process. The risk management file represents the totality of the device-specific risk documentation. b Risk categories: Annex I describes several safety requirements that an in-house in vitro diagnostic medical device (IH-IVD) must meet. These requirements are considered device specific in the risk assessment and the possible effects (yellow) are analysed

Fig. 5

Risk assessment based on an example in the category “use errors”. All identified risks are analysed accordingly. This is done in tabular form for all risk categories shown in Fig. 4b

Fig. 6

Definition of the performance characteristics to be determined using the example “MDM2/CEN 12—CISH”. Based on the intended purpose (Fig. 3), the scope of the validation is defined. It is checked which performance characteristics are applicable. Other performance characteristics listed as examples in Annex I, Chapter II, 9.1, are not applicable to this example

Fig. 7

Implementation of the Annex I requirements for in-house in vitro diagnostic medical devices (IH-IVD) in the established quality management system of the Institute of Pathology at Heidelberg University Hospital (IPH)