October 15, 2023

EU IVDR Compliance for In-House Lab Developed IVD Tests

When it comes to compliance with European regulations, manufacturers of in-house lab-developed tests have had it pretty good…along with most other IVD manufacturers. While the EU In Vitro Diagnostic Directive (IVDD 98/79/EC) exempted makers of so-called in-house tests (aka LDT), the new In Vitro Diagnostic Regulation does not carve out many exemptions for these tests. Still, without a single utterance of LDT in the entire IVDR, and no guidance documents published as of October 2023 many manufacturers are scratching their collective heads about what will be required and what to do next.

First, let us clarify what we mean by the generic term “lab-developed tests.” Although this specific term is not really used in the EU as it is in the US, there are two distinct types of in-house tests.

1 – Tests developed by and conducted at a health institution (for example, a biopsy tissue sample). A health institution is an organization whose primary purpose is the care or treatment of patients or the promotion of public health, and while the institution is placing an IVD “into service,” it is not placing the IVD “on the (EU) market.” IVDR Article 5 describes the specific requirements for these health institutions.

2 – Testing services where a sample is sent to a lab and a result is sent back (for example, a commercial genetic test using a saliva sample). Testing services are covered under IVDR Article 6 regarding Distance Sales and are treated the same as if the IVD was sold commercially (placed on the market).

This article focuses on testing services and Article 6. Some key points to understand:

So-called LDTs are not defined nor mentioned in the IVDR, but they are covered by it.
In order to be exempt from CE Marking, an in-house IVD must have no equivalent CE Marked IVD on the market.
The same classification system applied to IVDs applies to LDTs / in-house IVDs.
Compliance is not dependent on where the test is conducted.
At minimum, all tests must comply with the General Safety and Performance Requirements in Annex I of the IVDR.
Risk classification for an LDT / in-house IVD should follow the IVDR classification rules found in IVDR Article 47 and Annex VIII.
ISO 15189 will work for a health institution, but for testing services, ISO 13485 certification may be necessary.

IVDR Compliance for Commercial IVD Testing Services

Shown below is a quick reference table of compliance applicable for in-house tests where a sample is collected within the EU, then sent back to a lab inside or outside the EU.

Areas to Review	Required?
General Safety and Performance Requirements	Required, see Annex I
CE Marking of Test	Required, regardless of where actual testing is done
IVDR Classification of Specimen Receptacles	Class A
IVDR Classification of Tests	Class B, C, or D
Performance Evaluation	Required, see Article 56 and Annex XIII
Postmarket Surveillance (PMS)	Required, see Articles 78-79 and Annex III
Corrective and Preventive Action (CAPA)	Required under Annex I
Quality Management System Compliance	ISO 13485 is essential
Exemption for Research Use Only (RUO) Products	Must have no medical purpose

Are there any guidance documents to help understand IVDR requirements for IVD tests?

As of October 2023, there are no published guidance documents from the IMDRF related to compliance for these types of tests. This may change soon, and we recommend you monitor the European Commission page showing all current and planned EU MDR and IVDR guidance.

We ship CE Marked specimen receptacles to Europe but do the actual testing outside Europe. Do we really need to comply with the IVDR?

Yes. Even though specimen receptacles are considered Class A devices under the IVDR and can be self-certified, your test itself is no longer exempt and must follow IVDR classification guidelines found in Annex VIII, Article 47, and this guidance document. Also, it no longer matters where the actual test is conducted if your specimens are taken from European patients. Article 6 – Distance Sales specifically describes the need for compliance for testing services.

Is our IVD considered Research Use Only (RUO) and thus exempt from the IVDR?

Unlikely. MEDDEV 2.14/2 clearly defines Research Use Only (RUO) products, and to qualify under that definition, the test must have no intended medical purpose.

We have ISO 15189 certification. Do we really need to get ISO 13485 certification too?

If your IVD is Class B, C, or D, probably yes. The primary reason is that ISO 15189 certification focuses on the requirements for using in-house tests, whereas ISO 13485 adds requirements for manufacturing. As such, ISO 15189 does not cover all of the requirements of the IVDR. To be sure, consult with your Notified Body.

Want to Learn More?

If you need to get up to speed quickly on the IVDR, we have just the program for you. Our IVDR training class takes a deep dive into the nuts and bolts of the regulation and what your company needs to be doing right now to get ready. If you need to turbocharge your efforts, our IVDR consulting or ISO 13485 implementation teams are ready to hit the ground running and get you on the path to compliance quickly.