The analytical performance is described in European Union In Vitro Diagnostic Regulations (EU IVDR) 2017/746 as “the ability of the device to correctly detect or measure a particular analyte.” The analytical performance of any IVD/s is demonstrated based on the analytical performance studies, which are then documented as Analytical Performance Report (APR). The APR plays quite a crucial role in the Regulatory approvals of In Vitro Diagnostic medical devices, as this report is a part of the Performance Valuation Report (PER), which is further used as a conformity assessment. The analytical performance report is a comprehensive document that describes the testing and evaluation of the In Vitro Diagnostic medical device’s performance.
Section 9.1 of Annex I in EU IVDR describes the analytical performance requirements, which largely depend on the device type and intended purpose. It’s the manufacturer’s responsibility to provide a rationale for any characteristics that are not applicable to their device. Part A of Annex XIII in the EU IVDR provides a detailed requirement for writing APR. As a general rule, the manufacturer is first required to identify any available relevant data on the device via a thorough scientific literature review, pin down any unaddressed gaps and/or issues in the given data, evaluate it per the safety and performance of your devices and then generate any additional findings necessary to address the outstanding issues.
Further, the analytical performance of the in vitro diagnostic device is required to be demonstrated basis of the following parameters. Each of the parameters should involve a detailed description in a clear and legible format in the APR.
Accuracy of Measurement
The accuracy is mainly measured based on the trueness and the precision of the measurement. The trueness of measurement should describe the accuracy of the determined measurement process. The data should be summarized in detail to determine if the chosen methods are sufficient to establish accuracy. The trueness here applies to both quantitative and qualitative assays.
In the case of novel markers where the reference material or measurement is impossible to use for demonstrating trueness, different approaches are recommended use. For instance, the manufacturer can use other composite reference standards or relevant well-documented methods. In case of the absence of such approaches, the manufacturers can show a comparison between the novel device and the current standard practice on the same.
The precision of measurement should describe the repeatability and reproducibility of the data, meaning the measure is done on how reproducible the tests were when carried out multiple times without any alterations to the conditions. It helps in determining the ability to provide the exact required results consistently.
Analytical Sensitivity
This part should include information pertaining to the study designs and results. It includes information on the specimen type and preparation description, including matrix, analyte levels, and how levels were established. It should also contain information on the number of reproducibility tests conducted for each concentration and explain the calculation used for deducing the assay sensitivity.
Analytical Specificity
This section includes a description of interference and/or cross-references studies performed to determine the presence of any analyte in a sample. Information is provided on evaluating potential interfering and/or cross-reacting substances/materials on the assay, on the tested substance or agent type and its concentration, specimen type, analyte test concentration, and results.
Metrological Traceability of Calibrator and Control Material Values
This should include information on the values used for the measurement methods and materials.
Measuring the Range of The Assay
It includes information on the measuring range of the assays irrespective of the linearity/non-linearity of the measuring system, including the limit of detection. This section must also explain how the above data was deduced.
Definition of Assay-cut Off
It is the lowest analytical performance of a device that will allow the device to be approved and placed under EU IVDR. This part should also include detailed information on how this cut-off was deduced. It should cover the study design and methods, including the demographics, specimen characteristics, statistical methods, etc.
The APR might be a small section in the PER, but it holds immense value as it helps in establishing the safety and performance characteristics of the device, as well as the claims made by the manufacturer. This report is essential in assisting manufacturers and Regulatory Authorities in understanding the device’s risks and benefits and determining if the device meets the applicable requirements. Thus, writing an apt APR is quite crucial, and its failure can lead to hindrances in device approval and market entry.
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