An MDCG guideline for laboratory developed tests under IVDR
There have been a lot of discussions about what IVDR Art 5(5) means for genetic diagnostic labs. In January 2023, the Medical Device Coordination Group issued a guideline that clarifies important items. This is our summary.
The most important message at the beginning: Compliance with EN ISO 15189 does not constitute an appropriate QMS for the manufacture of LDTs. In our view this means that genetic testing labs must comply with the much more comprehensive EN ISO 13485.
Since Limbus is a medical device manufacturer under IVDR, we regularly evaluate IVDR related issues and documents. We frequently ask ourselves: What will this mean for our customers? Or how can we help our customers achieve compliance with IVDR? In this article, we will discuss the most recent MDCG Guideline 2023–1 that concerns health insitutions (and therefore genetic diagnostic labs).
Current regulation
Laboratory developed tests (LDTs) or “in-house devices” are regulated under IVDR since May 2022. The IVDR Preamble (29) defines LDTs as follows:
Health institutions should have the possibility of manufacturing, modifying and using devices in-house and thereby addressing, on a non-industrial scale, the specific needs of target patient groups which cannot be met at the appropriate level of performance by an equivalent device available on the market.
From the beginning, LDTs must meet the General Safety and Performance Requirements set out in Annex I of the regulation. The application of all other specific provisions of Art. 5(5) had been postponed until May 2024 to address the specific challenges of health institutions in the transition to IVDR.
Clarifications provided by the MDCG guideline
The MDCG 2023–1 guideline clarifies some items very explicitly and remains vague on other items. In the following, we highlight the most important provisions from our point of view.
Quality management system
Art. 5(5) IVDR states that health institutions must comply with EN ISO 15189. At the same time, however, the guidance clarifies that compliance with EN ISO 15189 alone does not constitute an appropriate QMS for the manufacture of in-house IVDs. We conclude that health institutions must therefore also comply with EN ISO 13485.
The QMS must also comprise the following processes:
- Examining the market for the presence and availability of equivalent CE marked devices before manufacturing an LDT.
- Carrying out a performance evaluation which is paramount to establishing proof of non-equivalency of available CE marked devices.
- Documenting the justification why the LDT is manufactured and used.
- Monitoring the market and updating its justification to continue to use the LDT on a regular basis.
- Collecting clinical and performance data.
- Processing incidents and corrective actions.
The target patient group’s specific needs
Point (d) of Art. 5(5) comes into effect only from May 2028. However, the guideline states that, if arguments are made that equivalent CE marked devices on the market do not meet the specific needs of the target patient group at the appropriate level of performance, these arguments must be supported by a thorough performance evaluation.
What constitutes a new medical device?
- Combining research use only (RUO) and CE marked devices. This is the case, for example, when using our CE marked software varvis® together with RUO wet-lab components or sequencing instruments.
- Changing CE devices, e. g. changing their intended use.
Legal entity
The guideline mentions that health institutions may consist of several different legal entities. It mentions two criteria that identify different legal entities:
- Different organizational numbers,
- Different quality management systems.
Industrial scale
The guideline is vague on the term “industrial scale”. It concedes, however, that performing diagnostic tests on a large number of patients does not necessarily mean manufacture at industrial scale.
The guideline suggests that health institutions should not build up large stocks of LDTs. The manufacturing process should not produce more than the estimated number of required devices.
