COVID-19 IVD quality problems drive EC guidelines

Regulatory NewsRegulatory News | 20 April 2020 |  By 

A “mismatch” between the expected and actual quality of coronavirus (COVID-19) tests has spurred new guidelines from the European Commission (EC). The guidelines are part of a roadmap to lifting the lockdown measures implemented to curb the spread of the disease across the European Union, according to an EC statement dated 15 April.
Governments across the European Union (EU) are working to step up testing capacity, recognizing that testing will play a key role in efforts to keep the virus under control as restrictions on populations are lifted. Companies have responded by introducing COVID-19 tests and scaling up their own operations to meet demand. Yet, along the way, EU officials think some organizations have failed to achieve expected standards.
“We have been working hard to analyze the information on the quality assurance of the coronavirus tests and devices that are currently being used. The results show that there is a mismatch between the existing quality and what could be expected to ensure good performance of the tests,” Mariya Gabriel, Commissioner for Innovation, Research, Culture, Education and Youth, said in a statement.
The mismatch has implications for European governments’ ability to lift lockdowns without causing a second surge in infections, according to the Commission. Governments will need reliable data current and previous infections to make decisions about which restrictions to lift — or reimplement — and when to do so.
To help EU member states gather the data they need, the Commission has created guidelines on the performance of in vitro diagnostic kits for COVID-19. All COVID-19 diagnostics are subject to directive 98/79/EC on IVDs but what that means in practice varies from test to test.
The guidelines
The guidelines divide COVID-19 tests into different subgroups for regulatory purposes. One division is between tests intended for use by healthcare professionals and those designed for use by patients.
The EU will allow the sale of tests to be used by healthcare professionals based on a declaration of conformity by the manufacturer. In contrast, self-testing devices must undergo verification by a notified body before coming to market. Tests that are made and used at the same health institution, which are known in Europe as “in-house devices,” need neither form of assessment at the EU level but may need assessment under by national legislation.
The guidelines also differentiate between tests designed to detect the virus itself or the remnants of an immune response against a now-resolved SARS-CoV-2 infection.
Many countries see a role for both types of test. Tests that identify active viral infections can inform decisions about when to quarantine an individual. Equally, antibody tests that show if someone has previously been infected may help governments decide whether to lift restrictions on individuals or the broader population.
The tests will only effectively fulfil those functions if they deliver reliable data. Having seen 78 tests for SARS-CoV-2 genetic material, 13 rapid antigen tests and 101 antibody tests receive CE marks as of early April, the EC has some doubts about the currently available diagnostics, as expressed by Gabriel.
To raise standards, the guidelines state manufacturers must make “state of the art” testing kits. The EC acknowledges that the state of the art in relation to COVID-19 is “evolving rapidly” but it wants companies to strive to be at the cutting edge “as far as reasonably possible.”
That does not mean all tests have to be best in class or excel in all areas. Rather, the guidelines call for companies to “not fall behind what can reasonably be achieved and is achieved by a majority of devices” and recognize that businesses will have to make trade-offs, for example between sensitivity and specificity, as they develop tests.
The EC wants manufacturers to consider the characteristics of their tests and how they will be used when making decisions about trade-offs. For example, the guidelines state a test with relatively low specificity may be acceptable if it is cheap enough to be used two or three times to compensate for that shortcoming. Manufacturers must explain their choices in the instructions for use.
In general, the guidelines provide a broad overview of the factors manufacturers and Member States should consider, rather than delivering detailed, prescriptive advice. That could change in the months to come, with the EC planning to hold talks about performance evaluations in the context of conformity assessments soon. The discussions, which will take place in the coming month and on a “regular basis” beyond that, could lead to guidance from the Medical Device Coordination Group.
Even if a manufacturer follows the existing guidelines, the EC thinks the test it develops may perform differently in the CE-marking study than in the real world. As such, the EC wants Member States to validate tests “by comparison with a reference method in a sufficiently large number of target population subjects before introducing the devices into the clinical routine.”
With all Member States potentially interested in the findings of validation studies, the EC sees “obvious benefits” to the sharing of data and the organizing of centralized assessments of tests.
Next steps
The creation of “a centralized overview of available information on test performance” is one of nine further required actions identified in the IVD guidelines.
In centralizing the information, the EC plans to assess the contexts in which the tests are used in the belief the information will help Member States make decisions about testing strategies. Further, they want “to foster a common EU approach, as far as this is appropriate.” Member States will retain ultimate control of their testing strategies, but the EC hopes they will consider similar factors, such as the relationship between the performance of a diagnostic and its intended use, when formulating their plans.
The harmonization of thinking across the region may be facilitated by the EC’s effort to align the approaches Member States use to assess tests. That effort will be supported by a push to establish COVID-19 reference laboratories across the EU to facilitate the exchange of knowledge and skills related to COVID-19 testing.
As manufacturers and Member States work to boost testing capacity, counterfeiters are capitalizing on consumer concerns about the pandemic and the lack of widely available authorized tests. National regulators have already identified “a number” of counterfeit tests that have “falsified proof of national registration, falsified notified body certificate or missing regulatory documentation,” according to the guidance.
In response, the EC plans to facilitate collaboration between regulators to support the identification and removal of counterfeits. They also call on national regulators to cooperate with importers and, in particular, distributors, as those stakeholders are well placed to identify trade in counterfeit COVID-19 tests.



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