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Establishment of guidelines by the Commission on “COVID-19 in vitro diagnostic tests and their performance” (OJEU C 122 1 of April, 15 2020)

 

 

Richard Milchior – April 17, 2020

 

 

In a Communication published on April, 15 the Commission seeks to organise and harmonise the development, production and use of Covid-19 in vitro diagnostic tests in preparation for post-confinement.

 

The Communication begins by pointing out that tests on a larger scale will be needed and that there must be a clear understanding of the information that the tests can provide and their level of performance.

The Communication then describes the regulatory context for in vitro diagnostic testing devices related to COVID-19 in the European Union (EU) and gives an overview of the different types of tests and their purposes. This includes considerations on the performance of these devices and their validation. It provides elements that should be taken into account both by Member States in defining their national strategies and by economic operators when placing devices on the market to ensure that, in the context of COVID-19, safe and effective tests are available in the EU.

The reminder on the regulatory framework states that tests are medical devices currently governed by Directive 98/79/EC and that their placing on the market requires compliance with the obligations of conformity laid down in that Directive leading :

– either the introduction of a CE marking affixed by the manufacturer in the case of tests intended for use by professionals,

– or to a marking verified by a “notified body” in the case of self-diagnostic tests.

However, one must keep in mind that in case of an emergency Member State may claim a derogation from these rules, implicitly under its own responsibility.

The Communication then describes the different types of tests, which fall into two categories: those detecting the SARS-CoV-2 virus and those detecting previous exposure to the virus (more precisely the human body’s immune response to the infection).

For the first category, there are two subtypes of tests: those that detect the genetic material of the virus (known as RT-PCR), and those that detect components of the virus, such as proteins present on its surface (antigen detection tests). It should be noted that these are rarely, if ever, mentioned on television, but this is because the WHO recommends the former and, according to the Commission, there are few antigen tests available.

Tests detecting exposure to the virus are generally those that look for antibodies produced in the blood by the patient’s body in response to infection with the virus. They are also called “serological tests”.

According to the Communication, if they are available on the market they are currently of limited effectiveness.

The Commission then distinguishes according to the type of technology between automated tests for use on analysis machines and rapid tests, defined as qualitative or semi-quantitative diagnostic devices, used separately or in a limited series, involving non-automated procedures and designed to give a rapid result.

It is reported in this Communication that there are still 78 RT-PCR tests, 13 rapid antigen detection tests and 101 antibody tests, most of which are rapid tests. It is also stated that their availability varies from one Member State to another and that some of them are intended for export only. It is by no means clear that any of these tests solve the current problems, hence the interest in the continuation of the Communication.

The Communication examines the appropriate performance criteria to be met by these tests, in particular in terms of analytical sensitivity, diagnostic sensitivity, analytical specificity, diagnostic specificity, accuracy, repeatability, reproducibility, including the control of relevant known interferences, and detection limits indicated by the manufacturer.

It also adds details on the information and instructions for use that must be provided and specifies that the technical documentation must contain adequate performance evaluation data in relation to a reference system and relevant studies.

In other words, it must be possible to evaluate each test in a scientific manner, so that they can be also compared with each other.

It is added that while a test should not “be the best in its class”, it should not perform below what can reasonably be achieved and is achieved by a majority of devices given the state of the art.

The Communication gives many more details on how to understand test performance and this data will be extremely important for both manufacturers and health authorities when deciding which tests to recommend, purchase or favour.

Once performance is established, the Communication indicates how this can be validated, especially in view of the rapid evolution of the pandemic.

It emphasizes that: ” Scientific peer-reviewed results for the clinical validation of commercial COVID-19 tests are highly recommended before they can be safely and reliably used for medical or public health decision making ” and also on their performance by the reference laboratories in the Member States and, of course, on the sharing of results at Union level and the centralised performance of validation studies in the Union, some of which are already under way.

The Communication then contains a long list of measures already taken with regard to market access and the performance of devices, divided into eight different chapters, seven of which can be described as positive measures aimed at solving the problem of having efficient and validated tests.

One of them, which is rather defensive, concerns the creation of channels of communication with other jurisdictions in order to fight against counterfeiting.

 

Finally, the Commission concludes with a list of nine sets of measures that are still necessary and are due to be adopted shortly.

While eight of them can be regarded as positive measures to facilitate research, cooperation, development and the placing on the market of tests, one can be described as defensive, since it aims to enable all Member States to combat together the counterfeit devices which have been placed on the market.

Future joint measures will include the exchange of information with the Member States with a view to defining their national testing strategy, but also the centralisation and communication of information by the Commission, the creation in the coming month of “best practices” with a view to evaluating the performance of tests, the establishment of a European network of reference laboratories, the coordination of stocks and the joint award of contracts.

It is clear that this Communication aims to facilitate joint development at EU level in order to avoid duplication of effort but also to try together to define the best testing system to speed up the recovery from the current crisis.

For once the Union has the opportunity to show that it can be a pilot and a coordinator. It will also have to be able to make this known so that, as is often the case, the Member States do not take credit for it.