Reclassifying a New Era in Laboratory Testing Regulation

Abstract

With IVDR coming into force in the EU, there has been a lack of clarity as to what it means and whom it will impact. IPM spoke with Amélie Martinez, who has been leading Saphetor's preparations for IVDR, to get some guidance on what the new regulation means for labs in Europe.

IPM: What are the main differences between IVDD and IVDR; and when will IVDR replace IVDD?

The Directive 98/79/EC for in vitro diagnostic medical devices (IVDD) was replaced by the (EU) Regulation 2017/746 on In Vitro Diagnostic Medical Devices (IVDR) on the 26th of May 2022.

The Directive is a legislative act that must be translated into the national law. Therefore, each state could interpret in their own way how to implement it.

However, the Regulation is a binding legislative act, and is immediately applicable in its eternity in all Member States, and it overrules national laws.

The main differences are the risk classification of the in vitro Diagnostic Medical Devices (IVD-MD) and the Safety and Performance that will now have to be systematically demonstrated through effective and objective evidence. The change on the risk classification has an impact on the CE marking process as now, the majority of the medical devices (IVD) will have to get an IVDR-certified Notified Body involved in the CE marking certification.

IPM: What determines whether a lab needs to be using a CE marked genomic analysis pipeline?

If the lab is using the genomic analysis pipeline to deliver a result to a patient, therefore the lab should use a certified one. If it's only for research, meaning no result will be used to provide feedback to a patient, then a “research use only” one is sufficient.

IPM: It seems that there is a lot of room for interpretation as to what can be considered “for research use”; is there a clear definition of what constitutes “clinical use” in the case of NGS analysis tools?

I would say that the clinical use is actually based on the medical device definition. As long as the results of the analysis are for the benefit of one particular patient, then it is a clinical use.

If we consider the NGS analysis tools, we first have to determine if they answer to the definition of a medical device, based on their intended use and indication for use.

Basically, a software will be qualified as IVD medical device if:

It uses input data resulting from the processing of the patient sample.

This analysis should have a medical purpose (concerning a physiological or pathological process or state, congenital impairments, predisposition to a medical condition or a disease, predict treatment response or reactions, or define or monitor therapeutic measures).

And lastly, this data is analyzed in order to provide a result to this individual patient (no gathered data).

IPM: Do labs running in-house pipelines have special dispensation as lab developed tests?

No, the in-house pipelines are also subject to meeting the IVDR requirements, and in particular Article 5.5.

The labs must:

Follow the Annex I of the IVDR, regarding the General Safety and Performance Requirements (GSPR) for their tool.

Have a Quality Management System in place which covers the use of the in-house pipelines.

Comply with the ISO 15189 regarding requirements for quality and competence in medical laboratories and get accredited.

Must not commercialize their tool.

Must justify that the target patient groups' specific needs cannot be met by an equivalent device available on the market.

Create the necessary documentation to justify the application of the GSPR such as design and performance data, intended use, risk management, etc.

IPM: What would a lab need to do to get their in-house pipeline CE marked under IVDR?

The following activities are part of the IVDR CE marking process. The list is not exhaustive, but highlights the main topics:

Have a certified quality management system following ISO 13485.

Identify and get a contract with a notified body.

Create the technical documentation for CE marking (intended use, risk management file, usability file, design and development plan, software requirement and specifications, architecture document, verification and validation plan), and all the test reports (unit test, integration test, system test, etc.), instruction for use, label (adding symbols on the software user interface), etc.

Set up a post-market surveillance process and a vigilance process.

IPM: When should labs start preparing for IVDR?

For a company that already has all the documentation ready and the quality management system certified according to ISO 13485, it takes around 24 months.

Note that, as of now, only six Notified Bodies certified for IVDR, meaning it gets very difficult to get a contract with one of them.

Gathering all the data for the demonstration of the safety and performance can take months.

Documenting all the activities is also very time consuming and depends on each team's efficiency.

The best advice I could give is to start now.

Whatever option the labs choose, in-house certification or CE marking, the IVDR has already entered into force.

IPM: Is there an advantage to using commercial products?

Obviously, this will reduce the burden of the labs that would avoid spending time, resources, and money in getting compliant to IVDR.

IPM: Why are regulations like this important?

The objective of the IVDR was to bring more transparency on the medical device and strengthen health safety and harmonize the rules applicable to medical devices (IVD) within the European Union.

It is very important for the patient's safety that all the medical devices and in vitro diagnostic medical devices are regulated following the same rules.

For more information visit saphetor.com