Regulatory Affairs Consulting for In Vitro Diagnostic Devices
Regulatory Affairs Consulting for In Vitro Diagnostic Devices
Key elements of the IVDR are the significant reinforcement of the risk classification, conformity assessment procedures, performance evaluation and performance studies, vigilance, and market surveillance while ensuring transparency and traceability. Due to the extended requirements for documenting the quality and conformity of the in vitro diagnostic devices imposed by IVDR, many manufacturers seek professional help in preparing the necessary documentation. The specific requirements of the documentation for IVDR are set in the main body and annexes of Regulation (EU) 2017/746. Our experts at New Criteria Consulting can help you prepare the necessary documentation and provide technical consulting during this process.
The initial step for demonstrating compliance is to go through the General Safety and Performance Requirements (GSPRs) that need support from clinical data. These requirements are explained in Annex I of the IVDR regulation (Regulation (EU) 2017/746). GSPRs are the basic requirements that are necessary to demonstrate the safety and performance of the devices. GSPRs need to be supported by performance evaluation and clinical data and need to be documented according to the IVDR.
To effectively assess the performance of any device, the first document that needs to be prepared is the Performance Evaluation Plan (PEP). For in vitro diagnostic devices, the manufacturers shall plan, conduct and document a performance evaluation in accordance with Article 56 of the IVDR and with Part A of Annex XIII. The clinical evidence that is documented should be able to support the intended purpose of the device as stated by the manufacturer and be based on a continuous process of performance evaluation, following a performance evaluation plan. According to the IVDR, the performance evaluation should follow a defined and methodologically sound procedure that is demonstrated by the scientific validity, analytical performance, and clinical performance of the device. The details of the requirements for the performance evaluation plan are described in Annex XIII.
The Performance Evaluation Plan will also form the basis of the Performance Evaluation Report (PER) which is described in IVDR Annex XIII. The clinical evidence should be documented in the Performance Evaluation Report, which should include the scientific validity report, the analytical performance report, the clinical performance report, and an assessment of those reports allowing demonstration of the clinical evidence.
The scientific validity of the device should be demonstrated by a Scientific Validity Report (SVR) that identifies the available data relevant to the device and its intended purpose through a systematic scientific literature review and identify any remaining unaddressed issues or gaps in the data and appraise all relevant data by evaluating their suitability for establishing the safety and performance of the device.
The Performance Evaluation Plan should also include a Literature Search Plan (LSP) which explains the literature search methodology that will be applied when performing the literature search and writing the Literature Search Report (LSR).
The analytical performance should be demonstrated and documented in the Analytical Performance Report (APR). It is the manufacturer’s responsibility to demonstrate the analytical performance of the device in relation to all the parameters described in point (a) of Section 9.1 of Annex I of IVDR unless any omission can be justified as not applicable. As a general rule, analytical performance should always be demonstrated on the basis of analytical performance studies.
The clinical evaluation of a device should be performed through a clinical performance study that will be performed in accordance with the ISO 20916:2019 In Vitro Diagnostic Medical Devices - Clinical Performance Studies Using Specimens From Human Subjects - Good Study Practice. These studies should be performed after obtaining an Internal Review Board approval. In order to apply for approval of such as study, the application forms should accompany Clinical Performance Study Plan (CPSP) and Investigator’s Brochure (IB). The investigator's brochure (IB) shall contain the information on the device for performance study that is relevant for the study and available at the time of application. Clinical performance studies should be performed on the basis of a clinical performance study plan (CPSP). The CPSP should clearly define the rationale, objectives, design and proposed analysis, methodology, monitoring, conduct, and record-keeping of the clinical performance study as explained in Annex XIII of the IVDR.
As per Annex XIII Section 2.3.3 of the IVDR, the Clinical Performance Study Report (CPSR) should be signed by a medical practitioner or any other authorized person responsible and contain documented information on the clinical performance study protocol plan (CPSP), and results and conclusions of the clinical performance study, including negative findings. It is imperative that the results and conclusions are presented transparently, free of bias, and clinically relevant. The CPSR shall contain sufficient information to enable it to be understood by an independent party without reference to other documents and include as appropriate any protocol amendments or deviations, and data exclusions with the appropriate rationale.
Post-Market Performance Follow-Up (PMPF) is a continuous process that updates the performance evaluation referred to in Article 56 and Part A of Annex XIII of the IVDR and should be addressed in the manufacturer's post-market surveillance plan. Before conducting PMPF, the methodology should be documented in a PMPF plan. PMPF should be conducted by the manufacturer by proactively collecting and evaluating performance and relevant scientific data from the use of the device with the aim of confirming the safety, performance, and scientific validity throughout the expected lifetime of the device. Its purpose is to ensure the continued acceptability of the benefit-risk ratio and detect emerging risks on the basis of factual evidence. The post-market surveillance report should be documented regularly depending on the Class of the device.
