In September 26th 2012, the European Commission proposed a draft for an in vitro diagnostic Regulation in order to overcome flaws and divergences in interpretation of the current IVD Directive 98/79/EC and to further strengthen patient safety.
Since then this draft have been amended by the European Parliament in October 2013 and the European Council provided its approved revision on September 21st 2015.
Following the trilogue, on May 25th 2016, The Netherlands presidency of the Council and representatives of the European Parliament agreed on new rules for in vitro diagnostic medical devices.
Although a political agreement has been reached, the new regulation will have to be approved by the Council and the European Parliament.
Until this approval and publication in the Official Journal of the European Union, anything can change, but we can already distinguish numerous new requirements that will be introduce by this regulation which will impact the IVD industry.
One of these major evolutions is for clinical evidence/performance evaluation requirements.
This newsletter will present the new clinical/performance evaluation requirements, for IVD products and manufacturer, introduce by this new regulation.
According to the draft of the political agreement, clinical evidence will have to be collected for all IVD devices. Clinical evidences are defined as clinical data and performance evaluation results pertaining to the device of sufficient amount and quality to allow a qualified assessment of whether the device achieves the intended clinical benefit(s) and safety, when used as intended by the manufacturer.
The performance evaluation are based on the assessment and analysis of data to establish or verify the:
- Scientific Validity
- Analytical performance
- Clinical performance
However compared to the current IVD Directive, the new regulation makes the need for clinical data and performance evaluation more explicit and prescriptive.
Performance evaluation requirements
The new regulation will require the manufacturer to develop plan and procedures to continuously perform, and document performance evaluations, with prescriptive frequency requirement for IVD devices in high risk classes (classes C and D).
ANNEX XII of the regulation specifies the type of information that should be included in the performance evaluation; this includes means of demonstration of scientific validity, clinical and analytical performances.
To collect these data the manufacturer will have to build up a performance evaluation plan, the ANNEX XII, also describe all elements that should be included in this plan. Although the manufacturer remains responsible to determine and justify the most appropriate mean of determination among the various recommended routes, the regulation provides the methodological principle that should be followed to determine scientific validity, analytical performance, and clinical performance.
In short, this include review of literature to identify available data relevant to the device and its intended purpose, as well as gaps in the data or remaining unaddressed issues, then appraisal of these data to establish safety and performance of the device, and finally implementation of performance evaluation plan to generate any new or additional data needed via performance studies.
Lastly, the manufacturer is required to evaluate data collected in these studies and make the link between these data and the conformity of the device as part of the performance evaluation and provide a performance evaluation report with specific information prescribe by the regulation.
Clinical performance studies requirements
As defined in the regulation and based on requirements of these studies, performance studies are the equivalent of clinical trials. As for clinical trial regulation on medicinal products for human use, the IVD regulation will require a performance study plan to define the rationale, objectives, design, and proposed analysis ,methodology, monitoring, conduct and record-keeping of the performance study.
Moreover, the Clinical performance studies for all IVD devices, including self-testing devices, will have to identify investigator and investigation sites, criteria and procedure for suspension or early termination of the studies, as well as criteria and procedure for follow-up clinical studies. These new provisions will require all subjects to have given an informed consent.
The new regulation also introduces provisions to perform clinical trials in different member states. In that case the manufacturer or its sponsor will make a single application which will then be submitted to all concerned member states, but coordinated by one member state. Under these new provisions, the decision taken by the coordinating member state will be deemed to be the conclusion of all concerned states.
Like it is required for clinical trial on medicinal products, all performance studies will require a clinical performance study report, which will include the study plan, results (positive and negative), and conclusions. These reports will have to contain enough information to be understood by an independent party without reference to other documents. Conclusion of this report will also be use as input to perform the performance assessment of the device.
Post-market performance follow-up
The reference to post-market performance follow-up (PMPF) is made in the purpose of performance evaluation as intended by the regulation, as planning of post-market performance follow-up will have to be included in the performance evaluation plan developed by the manufacturer to demonstrate the conformity of the device.
Moreover, conclusions which will be raised from post-market performance follow-up will be inputs of the performance evaluation review and report performed throughout the life-cycle of the device and for classes C and D devices annually.
Although it is important to remember that these information are extracted from the draft pf the political agreement on the IVD regulation and that information could be different on the final and applicable version of the regulation, the new IVD regulation will strongly emphasize on performance evaluation and clinical evidence and will require manufacturer to further collect, analyze, and document data pertaining to the clinical and performance of the device over the life cycle of the device. If you are interested to know more about the requirements presented above, do not hesitate to watch our free webinar below.