Clinical Performance Evaluation of IVD

In Vitro Diagnostic Kits Clinical Performance Evaluation

Clinical performance evaluation is the systematic study of a medical device that can be used to diagnose and treat diseases in vitro (IVD). It uses a specimen from human patients to measure its performance.

In vitro diagnostic medical instruments (IVDs) are designed to extract information from human samples such as blood and tissues that can allow for the drawing of conclusions, such as physiological or pathological changes in the body.

Clinical Performance Evaluation of IVD: Key Requirements

Classification Of In Vitro Diagnostic Medical Device

IVD classifications are determined based on the intended purpose of the devices.

Class A IVD Classification
Class A shall be assigned to an in vitro diagnosing medical device.

• If the article is a reagent and/or has any other specific characteristic that would make it suitable to perform an in vitro procedure for a specific examination,

• Instrument intended for use in vitro as a diagnostic tool;

• A specimen receptacle.

Class B IVDClassification
IVDs will be assigned to class B if it is intended that it is used to obtain.

• Test results not used to determine if a patient is medically-critical

• Preliminary test results need to be confirmed using appropriate laboratory tests

• This can be used to evaluate the performance of an analytic procedure or a part thereof. It does not have a quantitative assigned value.

Class C IVD Classification
If it is intended for following use, IVDs are classified as class C.

• How to detect the presence or exposure to a sexually transmitted drug

• Detecting the presence of infectious agents in cerebrospinal or blood fluids; or an incorrect result that can cause death or severe disability for the individual or the foetus

• Pre-natal screening for rubella/toxoplasmosis in women

• Screening patients for early signs of disease, and for the selection of patients to receive selective treatment or management.

• Human genetic testing for Cystic Fibrosis and Huntington’s Disease, including the testing for huntington’s disease and cystic fibrosis.

• Monitoring the levels of medicinal drugs, substances, and biological components. When there is a chance that an erroneous result could lead to a treatment decision that will cause immediate death for the patient being tested (e.g., cardiac markers, prothrombin or cyclosporin time testing).

• Management of patients with life-threatening infectious diseases like viral load of HIV and HCV

• Screening for congenital diseases in the foetus (spina bifida, down’s syndrome); intended for self-testing. It can also be used for near-patient testing, including a blood gas analysis, or a determination of blood glucose.

Class D IVD Classification
In vitro diagnostic medical device for the detection of the presence or exposure to transmissible agent

• It can be found in any blood or blood component, any blood derivative, cell tissue, organ, or cell. To assess whether the blood, component, or blood derivative is suitable for transplantation, cell tissue, organ or cell transfusion,

• This can lead to a life-threatening condition with high chances of spreading.

• If it is used for blood grouping, tissue typing according to ABO, then the Duffy system and the Kell systems, the Kidd system and the rhesus (for example, HLA Anti-Duffy, Anti–Kidd).

Application To Get The Grant Or Permission To Conduct Clinical Performance Evaluation Of New In Vitro Diagnostic Kit- Form MD-24

Permission from the Central Licensing Authority to perform any clinical performance assessment in relation to a new in vitro diagnosing medical device on any specimen, including blood or tissue derived directly from the human body, is required.

Risky In vitro Diagnostic Kits (Class B/C/D) are subject to a clinical performance evaluation without predicates. Although data on clinical performance evaluation for Class A IVD may not be necessary, in some cases, the Central Licencing Authority (CLA) may consider such data to be essential.

The IVD may be exempted from clinical performance evaluation if the regulatory authorities approve it of the United Kingdom, United States of America, Australia, Canada, and Japan. It is being marketed for at most two years in one of the above-mentioned countries. In these cases, however, the following must be met:

• CLA must be satisfied with data on safety, performance, and pharmacovigilance for the device that has been approved in each country.

• Based on existing knowledge, there should not be any evidence or the theoretical possibility of any differences in the behavior and performance of this device in Indians.

• The applicant must sign a written undertaking to conduct post-marketing studies with the goal of safety and performance of such IVD according to the protocol approved by CLA.

An application to grant approval for the clinical evaluation of new technology for in-vitro diagnosis of medical devices is made by the Central Licensing Authority in Form MD-24 by a company sponsor. The application must be accompanied by the details as specified in the Seventh Schedule of MDR 2022. The information needed is as below:

• An approval from the Ethics Committee, which is recorded with the Central Licensing Authority

• Quantity and source of samples that will be used in the evaluation

• Description of the device, including specifications of raw material and final product, information that allows the identification of the device and the proposed instructions for its use, and labels as well as regulations in different countries, if there are any.

• Performance evaluations in-house are used to determine the stability particularity, sensitivity, reproducibility, and repeatability.

• Clinical performance evaluation plans state specifically the objective for evaluation, the scientific, technical, or medical motives, and the range of evaluation.

• Case Report Form, as indicated in Table 6 in the Seventh Schedule.

• Investigators’ undertaking as defined in Table 9 in the Seventh Schedule

• List of laboratories and other institutions that are taking part in the study of evaluation

• The duration of the assessment and, in the cases of devices that self-test, the place and amount of lay people involved.

• An undertaking that the instrument that is being tested conforms to the specifications of these rules aside from the areas that are covered by the evaluation, and separate from the specific requirements set out in the declaration and that every step is taken to safeguard the safety and health of the user, patient, and others

• Evaluation of performance report from the laboratory that is designated under rule (1) in rule 19.

Permission to conduct IVD clinical performance evaluation - Form MD-25

The Central Licensing Authority, if satisfied that the conditions have been met, grants permission to evaluate the clinical performance of a new diagnostic in vitro medical device using the form MD-25. Once the permission has been granted, the clinical performance evaluation can begin based on the plans for evaluation of clinical performance approved by an authorized Ethics Committee.

Before beginning the enrollment process, the clinical performance evaluation must be recorded in the Clinical Trial Registry of India. The evaluation of performance in clinical trials must be mandatorily initiated by enrolling the first participant within one year following the granted permission in the absence of prior approval from the CLA before initiating the clinical evaluation of performance.

The annual status report for every clinical performance evaluation concerning whether the evaluation is ongoing, complete, or ended should be sent to CDSCO by the sponsor.

Reference

Medical Device Rule. 2017. MINISTRY OF HEALTH AND FAMILY WELFARE. (Department of Health and Family Welfare)