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Regulation (EU) 2017/746 on in vitro diagnostic medical devices (IVDR) has significantly tightened the requirements for the performance evaluation of in vitro diagnostic medical devices (IVD). Manufacturers are obliged to provide comprehensive evidence of the scientific validity, analytical performance and clinical performance of their products. This article provides a structured overview of the requirements and detection methods according to IVDR.
Definitions and basics
According to IVDR Article 2 (2), an in vitro diagnostic medical device (IVD) means “a medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, piece of equipment, software or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally for the purpose of providing information relating on one or more of the following
- concerning a physiological or pathological process or state,
- concerning congenital physical or mental impairments,
- concerning the predisposition to a medical condition or a disease,
- to determine the safety and compatability with potential recipients,
- to predict treatment response or reactions;
- to define or monitoring therapeutic measures.
Specimen receptacles shall also be deemed to be in vitro diagnostic medical devices;”
Since 26 May 2022, in vitro diagnostic medical devices (IVDs) have been subject to a new classification that divides them into four categories from A to D. This classification is based on the intended use of the product and the associated risks. The categorisation is based on seven specific classification rules (IVDR Art. 47 and Annex VIII). The risk to both the individual and the general public is taken into account. The greater the potential hazard, the higher the classification on the risk scale
| Risk class | Risk level | Examples |
| A | Low individual risk, low public risk | General microbiological culture media, buffer solutions, general staining reagents (e.g. haematoxylin, eosin) |
| B | Moderate individual risk, low public risk | Self-test during pregnancy, Urine test strips for the determination of urinary tract infections, assay for the detection of autoantibodies |
| C | High individual risk, moderate public risk | Blood glucose self-test, HLA typing, rapid test for the detection of methicillin-resistant Staphylococcus aureus |
| D | High individual risk, high public risk | Hepatitis B (HBs-Ag), hepatitis C (anti-HCV), human immunodeficiency virus 1/2 (anti-HIV 1/2) |
*HLA: human leucocyte antigens; PSA: prostate-specific antigens
The performance evaluation is mandatory for all manufacturers regardless of the risk class. It is defined in IVDR Article 2 (44) as the “assessment and analysis of data to establish or verify the scientific validity, the analytical and, where applicable, the clinical performance of a device”.
Performance evaluation process
In accordance with IVDR Annex XIII Part A, the performance evaluation process begins with the preparation of the Performance Evaluation Plan (PEP), which defines the objectives, methods and data sources for the evaluation
Three central aspects are then examined:
- the scientific validity that demonstrates the relationship between analytes and clinical condition
- the analytical performance, which ensures e.g. precision, specificity and reproducibility of the measurement, and
- clinical performance that confirms the practical utility of the test for medical decision-making.
All results are summarised in the Performance Evaluation Report (PER), which must be regularly reviewed and updated to ensure the safety and performance of the product
Scientific validity
The scientific validity of an analyte describes its suitability for the detection of a clinical or physiological state. In accordance with IVDR Annex XIII Part A 1.2.1, the manufacturer must demonstrate scientific validity using one or more of the following methods:
- Scientific literature
- Expert reports/opinions from relevant professional organisations
- Results of proof-of-concept studies
- Results from clinical performance studies
This requires systematic scientific literature research to identify relevant data and clarify open questions. The scientific validity is documented in the Scientific Validity Report (SVR).
Analytical performance
The analytical performance describes the ability of an IVD to correctly detect a specific analyte. According to IVDR Annex XIII Part A 1.2.2, the manufacturer must provide evidence of the analytical performance. The key parameters here are
- Analytical sensitivity (determination of detection limits)
- Analytical specificity (avoidance of interferences)
- Trueness, Precision, Accuracy
- Measuring range and linearity
- Cut-off values and criteria for specimen collection and handling
The Analytical Performance Report (APR) documents the analyses of analytical performance.
Clinical performance
Clinical performance describes the ability of an IVD to provide results that correlate with a clinical condition. According to IVDR Annex XIII Part A 1.2.3, the demonstration of clinical performance is based on:
- Clinical performance studies
- Scientific literature (peer review)
- Published experiences from the diagnostic routine
Clinical performance studies must be conducted unless an equivalent database can be demonstrated from other sources. The Clinical Performance Report (CPR) summarises the results of the clinical performance.
All evidence of scientific validity, analytical performance and clinical performance is included in the Performance Evaluation Report (PER), which covers additional aspects such as usability, durability, risk-benefit assessment and manufacturer’s claims.
All relevant data must be assessed by the manufacturer and checked for compliance with the general safety and performance requirements according to IVDR Annex I.
The IVDR places high demands on manufacturers to ensure the safety and performance of IVDs. A systematic, evidence-based approach is required to fulfil regulatory requirements and secure market access.
What about the scientific validity and analytical performance of Class A IVDs when no specific analyte is present – for example in centrifuges, sample containers or incubators? You will find answers to these and other questions in the upcoming posts in our IVD blog series.
A detailed interpretation of the legal requirements and information on the design of the performance evaluation can be found in MDCG 2022-2 (Guidance on general principles of clinical evidence for In Vitro Diagnostic medical devices (IVDs)). seleon can support you in planning and creating an IVDR-compliant performance evaluation!
Please note that all details and listings are not intended to be exhaustive, are without guarantee and are for information purposes only.
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