IVDCheckR - simplifying documentation for laboratory developed tests according to IVDR requirements by introducing a new digital tool.

OBJECTIVES: A recent challenge for clinical laboratories is the lack of clear guidelines for handling significant modifications of CE-marked assays. The modifications may involve, for example, extending measurement intervals, changing dilution procedures or using non-validated sample materials. The challenge arises due to the amended Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR), which is now poised for implementation, despite the extended transition periods. The IVDR application imposes challenges not only for diagnostic companies but also for clinical laboratories when using laboratory developed tests (LDTs), often referred to as in-house assays. In this context, a coherent and meticulously structured LDT documentation is highly beneficial. While laboratories are obliged to meet the IVDR requirements, the absence of a streamlined framework or guideline hampers the ability to gain a comprehensive overview on the requirements and possible options for their fulfilment. METHODS: To address this issue, we introduce a web based digital tool powered by an R Shiny web application. This tool facilitates a seamless implementation of IVDR requirements for LDTs across diverse laboratory environments in terms of their transparency and validity. Our approach focuses on adequate handling of significant modifications of CE-marked in vitro diagnostic medical devices (IVD). RESULTS: IVDRCheckR is an open-source tool that is easily accessible and free from system dependencies. The tool promotes a seamless process and a guide to enhance transparency, reliability, and validity of laboratory examination results based on LDTs. Additionally, the tool further provides modules for evaluating quality control data and quantitative method comparison data. CONCLUSIONS: Our Shiny web application-based platform is a digitised, user-friendly tool that simplifies the documentation for LDTs according to IVDR requirements with special emphasis on solutions for handling modifications to CE-marked assays.

Laboratory-Developed Tests: Design of a Regulatory Strategy in Compliance with the International State-of-the-Art and the Regulation (EU) 2017/746 (EU IVDR [In Vitro Diagnostic Medical Device Regulation]).

PURPOSE: This study aimed at the development of a regulatory strategy for compliance of laboratory-developed tests (LDTs) with requirements of the Regulation (EU) 2017/746 ("EU-IVDR") under consideration of international requirements for LDTs as established in major regulatory regions. Furthermore, it was analysed in how far elements of current LDT regulation could qualify for an internationally harmonised concept ensuring quality, safety and performance of LDTs. METHODS: A review of regulatory literature including legislation as well as guidance documents was performed. The regulatory strategy was adapted from international guidance concepts used for commercially marketed IVD. It was then applied to the example of a large medical laboratory in the EU. A high-level comparison was conducted to identify gaps and matches between the different international regulatory requirements for LDTs. RESULTS: A four-step strategy for compliance of LDTs with the EU IVDR was implemented in an exemplary medical laboratory. On the basis of an internationally used LDT definition, LDTs constitute nearly 50% of the total IVD devices used in the laboratory. While an ISO 15189-compliant QMS is a major component, it should be accompanied by the application of appropriate processes for risk management, performance evaluation and continuous monitoring of LDTs. At least six criteria represent common characteristics of a potential, internationally convergent concept for the regulation/standardization of LDTs. CONCLUSIONS: This study confirms the impact of LDTs for individualized and innovative medical laboratory testing. Prerequisites for LDT use as especially given by the IVDR and missing interpretation in the EU with regard to the scope of LDT definition, the application of standards and the extent of documentation for LDTs currently lead to uncertainties for both laboratories and regulatory bodies responsible for LDT oversight. The characteristics identified as common criteria for ensuring quality, safety and performance of LDTs may be considered as central elements of future international consensus guidance.

Advisory opinion of the AWMF Ad hoc Commission In-vitro Diagnostic Medical Devices regarding in-vitro diagnostic medical devices manufactured and used only within health institutions established in the Union according to Regulation (EU) 2017/746 (IVDR).

In view of the approaching application date of Regulation (EU) 2017/746 ("IVDR") and the resulting EU-wide, harmonized requirements for in-vitro diagnostic medical devices (IVD) manufactured and used within European health institutions, the Ad hoc Commission IVD of the German Association of the Scientific Medical Societies (AWMF) takes a national position on the details of the requirements and conditions related to the use of these IVD products. The Ad hoc Commission IVD emphasizes the relevance of examination procedures developed in medical laboratories, especially in the field of orphan diseases and new diagnostic markers. The IVDR sets an adequate regulatory framework for IVD manufactured and used within health institutions as long as these requirements are fulfilled with reliability and in accordance with the current state of the art in medical laboratory sciences. At the same time, the IVDR requirements have to be regarded under a pragmatic view and in accordance with the quality management systems approved within the different EU Member States. On the one hand, the mandatory requirements of the RiLiBÄK play an essential role in Germany. On the other hand, elements of voluntarily applicable international standards may support the fulfilment of product requirements for safety and performance according to Annex I of the IVDR. Both the complexity and possible solutions for the implementation of the IVDR requirements are discussed on the basis of examples such as the required documentation, performance evaluation and software validation. The Ad hoc Commission IVD recommends that, while aiming at a preferably EU-wide harmonized interpretation of the IVDR requirements, the flexibility in medical laboratory diagnostics necessary for patient care, including the use of IVD from in-house production, should be emphasized.