The European Commission, the EU authority responsible for medical devices regulation, issued guidelines dedicated to the diagnostic tests used in the context of the Coronavirus Disease 2019 (COVID-19) caused by the virus “SARS-CoV-2” or the “novel coronavirus”. The document covers the most important aspects related to the in vitro testing devices.
Scope of the EU Guidance
The outbreak of COVID-19 resulted in a significant increase in demand for in vitro diagnostic testing devices that could be used by a healthcare professional to identify the infected patients and therefore perform pandemic control.
In particular, the present guidance is focused on the two most important aspects:
- The intended purpose of the test indicated by the manufacturer on the basis of the information the test provides, and
- The actual accuracy of the test in question, its performance and effectiveness.
The document provides an overview of the currently applicable EU medical device legislation and describes in detail existing types of tests that could be used in the context of the COVID-19 outbreak. It also contains certain recommendations on regulatory measures the Member States should take into consideration when developing the national approach to the in vitro diagnostic medical devices of this kind.
According to the general rule, all COVID-19 tests are in vitro diagnostic medical devices that should be regulated under the Directive 98/79/EC. Thus, the manufacturer intended to make its testing devices available on the EU market should demonstrate compliance with the requirements set forth by the aforementioned Directive. First of all, it is necessary to provide a technical file confirming the compliance with the safety and performance requirements. Depending on the intended purpose indicated by the manufacturer, test could be designed to be used:
- Only by healthcare professionals – in this case, it would be sufficient to provide a declaration of conformity and to affix a CE mark indicating compliance with the applicable requirements.
- By patients (users) for self-testing – in this case, an additional verification should be performed by a notified body (an entity properly designated by the national regulating authority to perform compliance assessments of medical devices within the scope of designation).
At the same time, it is stated that in case if it is reasonably necessary to ensure public health protection, a national regulating authority of a Member State is entitled to allow for marketing and use (within its territory) the in vitro diagnostic medical device before performing all conformity assessment procedures. The decision on the implementation of such derogation should be based on the rigorous risk-benefit analysis. This approach should be used in cases when it is important to make the device available for immediate use.
Another exemption relates to the devices manufactured by the healthcare institution for its own purposes (in-house devices). In case if the device is intended for internal use only, certain regulatory procedures could be waived.
It is important to mention that the new In Vitro Diagnostic Medical Devices Regulation 2017/746 (IVDR) will replace the appropriate Directive after May 26, 2020. At the same time, during the transition period, IVD devices could be subject to compliance assessment in accordance with either Directive or Regulation.
COVID-19 Testing In Vitro Diagnostic Medical Devices
The document provides an overview of IVD devices used for COVID-19 diagnosing. To classify the tests, the following criteria are being used:
- The scientific rationale,
- The particular technology utilized,
- The intended user,
- The location of testing.
In accordance with the first criteria, the scientific rationale, testing devices could be divided into several categories and subtypes respectively:
- Tests intended to detect the virus SARS-CoV-2, including:
- Tests intended to detect the virus genetic material (based on the reverse transcription of the polymerase chain reaction – RT-PCR), and
- Tests intended to detect the components of the virus (antigen tests).
- Tests intended to detect the past exposure to the aforementioned virus (the immune response of the human body).
Nowadays most of the COVID-19 tests are based on RT-PCR technology, and the same type of tests is recommended by the World Health Organisation (WHO) and the European Centre for Disease Prevention and Control (ECDC). At the same time, antigen tests could be also used for the same purpose.
The tests of the second category allow to detect antibodies produced by the human body as a response to the infection. The use of such tests is limited due to the long period of time needed for the antibodies to become detectable (it usually takes several days). Thus, the accuracy of testing performed with such tests would actually depend on the sensitivity of the equipment and also on the immune system of the particular patient. It is also important to mention that antibodies could remain identifiable for some time even after the infection has been already cleared out, which also impacts the accuracy of testing making it difficult to identify whether the particular patient is infected or not and whether the patient could be contagious.
Depending on the technology the tests are based on, the following categories could be determined:
- Test for use on analyzer machines (automated test, most of the RT-PCR tests actually fall within the scope of this category), and
- Qualitative or semi-quantitative devices (rapid test, mostly antigen tests).
It is important to mention that antibody tests could fall within the scope of any of these categories.
As it was already mentioned before, depending on the intended user, tests could be intended to be used by healthcare professionals only or by general users (patients) for self-testing.
Depending on the intended location of testing, the test could be designed as laboratory-based or ones intended to be performed near a patient. At the same time, according to the applicable EU medical devices regulation, near-patient tests should be used only by healthcare professionals.
Additional Requirements Under the Directive 98/79/EC
According to the Directive 98/79/EC, medical devices comply with the safety and performance requirements. The latter should be evaluated taking into consideration such criteria, as:
- The analytical and diagnostic sensitivity,
- The analytical and diagnostic specificity,
- Accuracy, repeatability and reproducibility.
The manufacturer shall specify the intended purpose of a medical device on the labeling, and also in the instructions for use supplied with the device. The information contained therein should be clear and exhaustive, highlighting all important aspects.
The manufacturer shall also provide the following information:
- Performance levels for all parameters of the device,
- Reference methods and materials,
- Clinical studies data or the appropriate references,
- A confirmation that the device is based on the “state of the art”,
- The details on the sensitivity of the tests since this information is vitally important for healthcare professionals using it,
- The explanation of the performance levels,
- The indication of the target population.
It is important to mention that the actual scope of information to be provided by the manufacturer may vary depending on the particular category and type of tests. Thus, the requirements for RT-PCR tests and antibody tests could be different.
Summarizing the information provided hereabove, the EC guidance describes the regulatory approach for in vitro diagnostic tests intended to identify the virus SARS-CoV-2 during the pandemic.
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