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European Societyof Human Genetics
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ESHG POLICY STATEMENTRegulation EU 2017/746 (the IVD directive) is a threat to both precision medicine andcrisis management if the Article 5-§5 conditions (d)-(i) are not removed

Conclusion
ESHG strongly recommends that Article 5-§5 conditions (d) to (i) for in-house exemptions are removed
from the IVD directive, while conditions (a) to (c) are kept. Failure to do so will increase health care costs
and jeopardize our ability to design precise “personalized” laboratory tests (necessary for precisionmedicine) and to adapt to shifting test needs (like repurposing instruments for covid-19 testing).
Background
Regulation EU 2017/746 on in vitro diagnostic medical devices (the IVD directive) will be European law
from May 26th, 2022. The intentions of the legislators have been appropriate: to secure quality of all
kinds of medical diagnostic tests, and to make sure such tests are performed within the frame of thehealth care system. An apparently convenient means to obtain this is to demand industry standard CE
marking of tests and instruments.
In-house exemption to CE marking
Since CE marking is too cumbersome and expensive for the low-volume specialized tests designed inmany diagnostic laboratories, also as part of precision medicine, an in-house exemption to therequirement for CE marking has been made (article 5-§5). Such in-house tests are very common in
medical genetics. However, this in-house exemption can only be invoked if several conditions are fulfilled(numbered a-i). One condition is that the laboratory must be accredited according to EN ISO 15189 or asimilar nationally approved system. This condition makes much sense since such accreditation
automatically implies quality management and risk evaluation (other requirements). More problematic,
however, is condition (d): “the health institution justifies in its documentation that the target patientgroup’s specific needs cannot be met […] by an equivalent device available on the market”. In otherwords: If a CE marked commercial test exists that gives similar test results, that test must be used – andcost is not an issue.
Precision medicine out of control
So far commercial CE marked tests for rare conditions are exceptional, likely because the “market” is toosmall, i.e. not worth the investment. This may change when next generation (whole-exome or wholeIBAN: AT 93 20111 280 365 803 12 – SWIFT/BIC: GIBAATWW
Account 'ESHG', Account Number: 28036580312, Bank Code: 20111
Erste Bank, Alserstrasse 23, 1080 Vienna, Austria

-2-genome) sequencing (NGS) is established as the basis for all kind of rare disease diagnostics;
companies that now label their sequencing instruments “for research use only” may suddenly introduce a
CE marked diagnostic “NGS-package” using the same instruments that will return a standardized set ofsequencing data for local interpretation, like they have done for NIPT (non-invasive prenatal testing).
This will turn in-house laboratory skills into an unaffordable luxury.
Furthermore, it will be too expensive to develop test reagents (like unique FISH probes) since thedocumentation requirements for non-commercial reagents in the IVD-directive goes beyond ISO 15189.
The need for control measures that goes beyond EN ISO 15189 has not been documented as necessary
for securing good laboratory quality. Practice in line with the well-established ISO-standard is in our view
a sufficient quality control. We are, however, unsure if it is wise to allow national exemptions to thisstandard, like Article 5-§5 now allows. If Article 5-§5 stays as it is, commercial interests will govern
precision medicine, and patient interests will suffer because in-house personalized testing will not bepossible.
Let us keep the flexibility and creativity alive
Standardization is fine if you want to mass produce a car, but not if you suddenly need to find a creativesolution to novel problems in patient diagnostics (as part of precision medicine) or pandemic control (toenhance covid-19 test capacity). The ability to rapidly repurpose testing was crucial to obtain pandemic
control in Europe, and here Europe had an advantage over the more rigorous US system. Let us not lose
this capacity because a too rigorous IVD directive becomes EU law. That would really be a threat topublic health.
On behalf of the Executive Board of the European Society of Human Genetics

Gunnar Houge MD PhD
Vice-president

IBAN: AT 93 20111 280 365 803 12 – SWIFT/BIC: GIBAATWW
Account 'ESHG', Account Number: 28036580312, Bank Code: 20111
Erste Bank, Alserstrasse 23, 1080 Vienna, Austria