EU IVDR 2017/746: Impact to Clinical Laboratories and Drug Developers
How central labs can mitigate IVDR impact
The In Vitro Diagnostic Medical Devices Regulation (EU) 2017/746 (IVDR) took effect on May 26, 2022, repealing the In Vitro Diagnostic Medical Devices Directive 98/79/EC (IVDD). The IVDR defines the requirements for development, clinical studies, Conformité Européene assessments (CE marking), and commercialization of in vitro diagnostics (IVDs). While IVDR is legislated for European Union member states, other EU countries may recognize IVDR due to various EU agreements.
IVDR impact on drug developers and clinical laboratories
When fully implemented, the IVDR will provide significant improvements for diagnostic testing for healthcare providers and patients in the EU. However, in terms of drug development in the EU, the IVDR has presented challenges for sponsors of EU medicinal clinical studies and clinical laboratories that provide central lab services.
Key IVDR challenges include:
- IVDR does not recognize the role of central labs that support global medicinal clinical studies by offering specialized tests for medical decision-making when there is no commercial test meeting the needs of the study. Under IVDR, only health institutions located in EU member states can support development of specialized tests (such as in-house devices and modified commercial tests) for medical decision-making without obtaining prior approval from EU National Competent Authorities (NCA) and EU member state ethics committees (ECs).
- Central labs must apply IVDR’s interventional clinical performance study regulatory pathway when developing specialized tests for medical decision-making. This pathway requires prior approval by EU NCAs and EU member state ECs prior to use within the medicinal study. As a result, this pathway greatly increases the regulatory burden of conducting clinical studies in the EU and may result in study delays.
- To allow IVD manufacturers additional time to CE-mark their tests under IVDR, the EU parliament authorized extensions for tests that were CE-marked under IVDD. While these extensions are critical for ensuring continued supply of IVDs in the EU, the extensions have necessitated careful management of CE-marked test selection and monitoring of continued availability of CE-IVDD tests by the central lab.
Mitigate IVDR impact via central labs
To mitigate the challenges introduced by IVDR for drug developers, central labs must be willing to expand their services and test offerings to support EU medicinal study sponsors by:
- Developing an in-depth understanding of the requirements and limitations of different types of IVDR-compliant tests to better support clients (i.e., CE-IVDD, CE-IVDR, in-house device, modified CE-marked test, test for interventional clinical performance study).
- Implementing an ISO 13485 quality management system to offer tests compliant with IVDR’s interventional clinical performance study pathway and supporting required clinical trial applications and ethic committee submissions.
- Expanding test menus to provide IVDR-compliant tests in support of key therapeutic areas and technologies and further minimizing gaps in test menus by partnering with and qualifying EU third-party labs (including some certified as health institutions).
- Training operations and study support personnel to ensure effective implementation and monitoring of IVDR compliance for all impacted tests/studies post-award.
- Developing IVD partner alliances to proactively support development of CE-IVDR tests.
As an example of expanding test menus under IVDR, central labs previously running a commercially available “Research Use Only” comprehensive genomic profiling sequencing panel validated as a laboratory-developed test, or LDT, would need to onboard and verify the 517 gene, CE-IVD version of that assay in order to support detection of DNA and/or RNA mutations for medical decision-making in EU clinical oncology studies.
Building on understanding of IVDR requirements
Although IVDR has been challenging to drug developers and clinical lab teams alike, by applying an in-depth understanding of requirements for IVDR compliance along with a willingness to expand test offerings and provide regulatory services, labs can effectively mitigate the impact of IVDR for EU medicinal study sponsors.