In-Vitro Device Regulation

On April 5th,2017, the European Parliament replaced Directive 98/79/EC on In Vitro Diagnostic Medical Devices (IVDD) with the new Regulation (EU) 2017/746 on In Vitro Diagnostic Medical Devices (IVDR). The IVDR entered into force on 26 May 2017 and after a transition period, the IVDR went into force on 26th May 2022, and medical devices must now meet the requirements of the MDR to be placed on the European Union market.

The IVDR aims to enhance patient safety and ensure the reliability and performance of In-Vitro Diagnostic Medical Devices (IVDs) introducing more stringent requirements for manufacturers, focusing on risk classification, clinical evidence, and post-market surveillance. The regulation has a broad impact, encompassing all manufacturers of IVDs, ranging from lower-risk Class A devices to higher-risk Class D devices embracing a lifecycle approach that underscores activities spanning from design and production to post-market surveillance.

On 25th January 2022, amendments (Regulation (EU) 2022/112) were made to the IVDR, incorporating an updated transitional period outlined in Article 110. This revision introduces staggered deadlines based on the risk class of the device extending the compliance timeframe until 2028. In detail, this extension applies to devices undergoing the transition from the MDD to the MDR within the following timelines:

• 26th May 2025: all IVDD CE-certified devices and all Class D self-declared (with no notified body involvement but needing an IVDR certificate) IVDD devices must comply with the IVDR.

• 26th May 2026: Class C self-declared IVDD devices must comply with the IVDR.

• 26th May 2027: Class B and Class A sterile self-declared IVDD devices must comply with the IVDR.

To be eligible for the transition extension and to place the IVDs on the market or put into service until the above-mentioned dates, the self-declared IVDs that require the involvement of a NB must meet the following conditions:

• A declaration of conformity issued under IVDD before May 26th, 2022, and continue to comply with Directive 98/79/EC

• IVDs should not undergo any significant changes to the design, manufacture, or intended purpose.

• Need to implement a Post-Market Surveillance Plan in accordance with Annex III

• Develop a PMS Report or a Periodic Safety Update Report (PSUR) (Articles 78-81)

Performance Evaluation

According to IVDR Annex XIII, the performance evaluation is a continuous process conducted throughout the life cycle of an IVD. In that, data are assessed and analyzed to demonstrate the scientific validity, analytical performance, and clinical performance of the IVD for its intended purpose as stated by the manufacturer. The IVDR requires that the performance evaluation must be thorough and objective, considering both favorable and unfavorable data. Importantly, its depth and extent must be proportionate and appropriate to the characteristics of the device including the risks, risk class, performance, and its intended purpose.

• Performance Evaluation Plan

To systematically plan, conduct, and document performance evaluations, the manufacturer must create and regularly update a comprehensive performance evaluation plan (PEP). This plan should outline the device's characteristics, performance metrics, and the methods and criteria employed to generate essential clinical evidence.

The manufacturer needs to identify and evaluate the available data in terms of their suitability and relevance for demonstrating conformity with the relevant GSPRs and intended purpose. Importantly, the need whether additional scientific validity, analytical performance, or clinical performance data is required to demonstrate conformity, and identification of any unaddressed issues or gaps that exist in the available data are to be identified. If needed, data needs to be generated before the submission of the TD.

• Performance Evaluation Report

The Performance Evaluation Report (PER) includes the scientific validity report, the analytical performance report, the clinical performance report, and a qualified assessment of those reports allowing demonstration of the clinical evidence of whether the device will achieve the intended clinical benefit and safety when used according to the instruction of use.

Post-Market Performance Follow-Up

When conducting Post-Market Performance Follow-Up (PMPF), the manufacturer proactively collects and evaluates performance and relevant scientific data from the use of the IVD which bears the CE marking and is placed on the market or put into service within its intended purpose. PMPF aims to confirm the safety, performance, and scientific validity throughout the expected lifetime of the device, ensuring the continued acceptability of the benefit-risk ratio and of detecting emerging risks based on factual evidence.

• PMPF Plan

The PMPF plan specifies the methods and procedures for proactively collecting and evaluating the IVD's safety, performance, and scientific data. Overall, the PMPF plan aims to confirm the safety and performance of the IVD throughout its expected lifetime by identifying previously unknown risks or limits to its performance and contra-indications. Further, the PMPF addresses the identification and analysis of emerging risks, and possible systematic misuse, and ensures the continued acceptability of the clinical evidence and the benefit-risk ratio. Among other requirements, the PMPF plan must define general and specific activities. While the general activities have a broader perspective focusing on, for example, feedback from users or screening of scientific literature databases, the specific activities aim to answer distinct aspects or questions to collect sufficient clinical evidence data for conformity with the GSPRs. Here, the manufacturer defines, for example, epidemiological studies, evaluation of suitable patient or disease registers, and genetic databanks.

• PMPF Report

The findings of the PMPF activities laid out in the corresponding PMPF plan need to be documented in a PMCF evaluation report. Importantly, the conclusions of the PMPF evaluation report need to be considered to update the upcoming performance evaluation and the manufacturer's RM.