This series of digital engagements highlights how targeting pathogenic gene fusions can improve patient outcomes:

The clinical utility of NRG1 fusions as a poor prognostic factor across tumor types, exploring NRG1+ tumors’ metastatic potential and histological features

Testing for NRG1 fusions in cancer patients, focusing on the importance of targeted NGS approaches and RNA-based NGS

As we conclude this series, catch-up on various activities so far:

 into the molecular biology of NRG1 fusions and explore its clinical relevance

to Dr Pranil Chandra discuss the clinical utility of NRG1 fusions and how to test for them using targeted NGS approaches and RNA-based NGS during the Lab Talk "Testing for NRG1 fusions: The new kid on the block of actionable pathogenic gene fusions"

key insights about RNA-NGS (RNA-based Next-Generation Sequencing) and its importance in detecting pathogenic NRG1 fusions

 the FAQs from the series and the slides from the Lab Talk. These can be printed for ease of reference.

 shed light on pathogenic gene fusions and the significant clinical utility of NRG1 fusions as key actionable pathogenic gene fusions which have been identified across many tumor types. The message highlighted the importance of comprehensive testing with RNA-based NGS being the optimal methodology to capture pathogenic gene fusions.

(Senior Vice President, Chief Genomics Officer, PathGroup), exploring NRG1 fusions - The new kid on the block of actionable pathogenic gene fusions. To further support labs in NRG1 fusions testing Dr Chandra discussed how to properly test for NRG1 fusions in cancer patients, focusing on targeted NGS approaches and RNA-based NGS.

, and detecting them can improve patient outcomes.

RNA-NGS (RNA-based Next-Generation Sequencing)

 is more effective than DNA-only NGS in identifying actionable gene fusions.

Clinical guidelines (e.g., ESMO, ASCO) recommend RNA-NGS

 for detecting gene fusions, including NTRK fusions, due to its superior sensitivity.

 are emerging as actionable targets linked to poor prognosis, highlighting the importance of comprehensive RNA and DNA profiling.

RNA-NGS and DNA-NGS together enhances the detection of structural variants

, providing expanded therapeutic opportunities for patients.

Thank you for joining us throughout the series!

If you have any questions on this series or would like to learn more about the DXRX Network, contact help@dxrx.io.

Over the past few months, Diaceutics have delivered a series of digital activities focusing on testing of NRG1 fusions - The new kid on the block of actionable pathogenic gene fusions.


Spain got its first Notified Body (NB) in February when the Centro Nacional de Certificatión de Productos Sanitarios (CNCps) received its designation. The Irish NB The National Standards Authority of Ireland (NSAI) had its designation temporarily suspended in December 2024 but was reinstated on 18 March 2025 after process improvements identified in an audit were put in place. There are, therefore, currently 14 NB listed as active and able to take on certification work. There is likely still not enough NB to provide conformity assessment to all devices that require it, especially given the time taken for the process. Estimates of the time taken for certification vary: one survey found that 75% of devices received certification in 13-18 months with 17% taking 19-24 months with the chief limitations being the tightened regulatory requirements and limited time and capacity of notified bodies. These problems are exacerbated by the fact that many manufacturers may be interacting with a NB for the first time and are unfamiliar with several of the processes involved. Also, in order to maintain impartiality, NB are not allowed to act as consultants to clients for whom they are undertaking conformity assessments – they can’t “coach” a client through the process.
NB may refuse or return applications and the most common reasons are: outside of the scope of the NB, wrong classification of the device, wrong conformity assessment procedure or incomplete application.
The structure and quality of the technical documentation supporting the application can also be problematic, again made worse by an applicant’s unfamiliarity with the process and the documentation required. Here, the role of consultancies with expertise in the field, but not acting as NB, may be vital to help manufacturers get the certification they need for their products but will likely add considerably to the costs and possibly be in short supply.
Certification costs vary considerably among NB with flat fees for application of the order of several thousand € and separate fees for certification audits and assessment of technical documentation running several hundred € per hour or several thousand € per day depending on the NB.Overall, certification costs could be a minimum of €50k with the potential to go much higher, an even higher if consultancy is required.The EU mandates that all NB publish their fees for the sake of transparency and this information is available 


So, a lot of the issues with NB are still present and it remains to be seen how many low margin products become economically unsustainable because of regulatory costs and are, therefore, pulled from the market.

EUDAMED – the plot thickens…or does it?


So far just 3 out of 6 EUDAMED modules are operational and that only on a voluntary basis. These are:
- Actor Registration: Information on manufacturers, importers, distributors, and other relevant parties.
- UDI/Device Registration: Details on unique device identifiers (UDIs), device classification, and registration.
- Notified Bodies and Certificates: Information about notified bodies and the certificates they issue.
The other 3 modules are:
- Vigilance: Reporting of adverse incidents and recalls.
- Market Surveillance: Oversight of medical devices on the market.
- Clinical Investigations and Performance Studies: Data on clinical trials and performance studies.

It is anticipated that use of the first 3 modules, and of the market surveillance module, will become mandatory some time in 2026 with the timeline for use of the remaining 2 modules uncertain but possibly late 2026 or 2027.

In addition to huge delays – EUDAMED was intended to be operational in 2021 – there have been allegations, somewhat contentious, that the costs related to development of the databases and systems have spiralled, that the project is over time, over budget and over staffed. Whether these allegations are unfounded or not, there are still many uncertainties over how, and on what timescale, EUDAMED will become fully operational.


The EU Commission called for feedback on both the MDR and IVDR with a consultation period extending from 12th December 2024 to 21st March 2025 and adoption of “fine tuning” of the regulations due in Q4 2025.There are currently 398 responses and, according to Medtech Insight, the Commission has faced a “torrent of criticism” of the regulations. Recurrent themes in the feedback include the complexity of the regulations, the difficulty and cost of their implementation (see comments about consultancy, above) and their potential to stifle innovation.
Once the consultation is closed, we’ll analyse the feedback in terms of the problems labs are having with implementing the regulations for laboratory developed tests (LDT, also called the in-house exemption, Article 5.5 IVDR) and present this as a special review.


In December, the EU provided guidance on “The Information Obligation in Case of Interruption or Discontinuation of Supply of Certain Medical Devices and 

 Diagnostic Medical Devices”. As of 10th January 2025, manufacturers will have to inform the EU if they anticipate an interruption in the supply of a device or intend to discontinue it in the EU if the non-availability of the device carries a risk of serious harm to patients or public health in one or more member states of the EU. Completed notifications will have to be cascaded down through economic operators e.g. distributors to final customers. Notification must be provided at least six months prior to anticipated interruption or intended discontinuation.
Included in the guidance as the phrase “It should be noted that serious harm can also be due to the 

inability of a healthcare professional to deliver a specific medical treatment due to an interruption or discontinuation in the supply of a device

.” (our emphasis).This may have special relevance in the case of companion diagnostics where the non-availability of a specific test may interfere with the use of the therapy which is gatekeepered by the companion diagnostic.
However, the regulation does not apply to “custom-made devices”.While not clear, this, and application of the regulation to manufacturers, suggests that labs who make LDTs covered by the in-house exemption may not have to comply with the notification requirements.

So, problems remain with NBs, EUDAMED is still problematic and well behind schedule and a lot of very unhappy people have told the EU what they think of the regulation.

As we move into 2025, the regulatory landscape for IVDR continues to evolve. In 2024, we shared the updates on the upcoming changes and now we’re providing the latest insights in 2025 to ensure you stay informed and prepared.

The goal of Precision Medicine in oncology is to identify the right patient, for the right therapy, at the right time. 

Patient characteristics drive treatment decisions that are most likely to provide benefit.

Targeting pathogenic gene fusions can improve patient outcomes. 

In an analysis of 79 patients with identified gene fusions, poorer outcomes were observed in patients with pathogenic gene fusions who were not matched to an FDA-approved fusion-targeted therapy.

comprehensive profiling at the DNA and RNA levels (RNA-based NGS)

provide patients with therapeutic opportunities beyond standard treatments.

from PathGroup explored pathogenic gene fusions as oncogenic drivers and actionable biomarkers in precision oncology, focusing on NRG1 fusions. The session covered the 

 as a poor prognostic factor across tumor types, exploring 

 and histological features. Dr. Pranil Chandra from PathGroup also 

discussed how to properly test for NRG1 fusions in cancer patients

, focusing on targeted NGS approaches and RNA-based NGS.

defines cancer according to its genomic profile rather than by the organ or tissue of origin

select treatments most likely to benefit the patient

NRG1 is an important pathogenic gene fusion 

and is reported to be associated with poor outcomes

NRG1+ tumors possess aggressive histological features 

associated with increased tumor growth, invasiveness, 

recurrence, resistance to therapy, metastasis, and worse prognosis

Comprehensive testing with RNA-based NGS, including DNA and RNA sequencing, is recommended to detect NRG1 fusions

 due to its diversity of gene fusion partners and breakpoints and its large intronic region

Concurrent RNA-NGS and DNA-NGS testing should be used clinically to maximize structural variant detection relative to DNA-NGS alone

Click here to watch the Lab Talk recording now.

Thank you for joining us so far! Stay tuned for more insights on NRG1 fusions!

Download the testing for NRG1 fusions FAQs here.

Over the past couple of months, Diaceutics have delivered digital activities focusing on testing of NRG1 fusions - The new kid on the block of actionable pathogenic gene fusions.

Exploring Inherited Cancer: from clinic to lab. 

In episode 7 of the 'Better Testing, Better Treatment' podcast, we are thrilled to welcome our guests Anna Considine, Consultant Cancer Genetic Counsellor and Samantha Butler, Principal Clinical Scientist, from the Birmingham Women and Children’s NHS Foundation Trust and the West Midlands Regional Genetics Service.

Anna Considine and Samantha Butler explore how genetic testing for inherited cancer has evolved over the last 20 years, transforming both clinical practice and patient care.

Don't forget to catch up on previous episodes in the series!

Listen now

We are excited to announce that our seventh episode is available now.

Finally, Another Notified Body Announced.


Istituto Superiore di Sanita, based in Rome was announced as the 13th Notified Body (NB) in September, nearly a year after the previous new addition. ISS is the first NB in Italy. There are now 4 in Germany, 2 each in Finland and The Netherlands, and 1 each in Austria, France, Italy, Ireland and Slovakia. The low numbers of NB still represent a significant potential road block to the full implementation of IVDR yet, ironically, there are now reports that these NB may have spare capacity as manufacturers delay their applications in order to pursue regulatory submissions in other jurisdictions or wait to see what happens as a result of the extension to full implementation.


The European Commission has further extended the deadlines for full implementation of IVDR.As with the previous extension, the new one will be staggered according to device classification meaning implementation for Class A and B devices won’t occur until the end of the decade. 

EUDAMED: Mandatory Registration, At Least for Those Bits That Work

According to the European Commission: “EUDAMED is the IT system established by Regulation (EU) 2017/745 on medical devices and Regulation (EU) 2017/746 on in vitro diagnosis medical devices. EUDAMED is integral part of the implementation of the two Medical Devices Regulations.” It is structured around 6 modules and a public website but currently only 3 modules are available with the rest varying times away from deployment. The Commission has decided that IVD manufacturers will need to begin registration with those modules of EUDAMED that are deployed from Jan 2026 instead of waiting for the entire system to become available. Industry bodies have expressed concerns that manufacturers are not devoting sufficient resources to training users and preparing documentation for inclusion in EUDAMED and advise them to address registration on the system as soon as possible.
Included in mandatory notifications for manufacturers is a requirement for them to notify the EU or their Competent Authorities if an IVD is at risk of becoming unavailable.

Despite Progress and Extended Deadlines, There’s Still Concerns

Various groups have been expressing concerns about the slow implementation speed and complexity of both the MDR and IVDR.
A group of 29 national associations and the EU-wide industry association MedTech Europe sent an open letter to the Commission, via its outgoing Commissioner for Health & Food Safety, requesting action to ensure device availability and competitiveness. They also had this to say about the two regulations:
“The unpredictability, complexity, and burden of the regulations means that many devices on the market today as well as new, innovative medical technologies are not reaching patients in Europe as they should. The competitiveness of the wider industry and even the viability of many small businesses (SMEs) are at risk.”

They pointed out that the incoming regulatory process is complex, slow and overly bureaucratic, hampering companies who are trying to bring new products to market. This limits innovation and availability of cutting-edge products to EU patients, while reducing their competitiveness.

The industry associations also called for a series of bridging measures to “…halt the continued disappearance of devices from the EU market and for attracting investment in bringing innovations to Europe”

Industry isn’t the only group with concerns. Members of the European Parliament (MEPs) have also expressed their concerns about the medical device and IVD regulations. According one MEP, the EU “…has introduced "loads of rules" that do not increase safety, but cause expense and effort to rise and that costs us jobs and economic growth at a time when the European economy is in a crisis situation”, creating a “bureaucratic monster” in the process. The EU parliament called on the incoming Health Commissioner to “step up” the implementation of the current regulations and evaluate the need for potential changes otherwise MEPs agreed, MEPs agreed, Europe's (EU) competitiveness will further decline, industry will pay and patients will suffer further shortfalls in care.

After different delays and not without concerns, the implementation of IVDR, the new regulatory framework for in-vitro diagnostic in the EU, has now started. Molecular testing in oncology is likely to be one of the areas in which this legislation will have a bigger impact, with questions and concerns having been raised by all the stakeholders involved in biomarker testing. However, IVDR is here to stay, and laboratories are facing a transition period in which they will need to adapt to this new reality.

Insights

Testing for NRG1 Fusions - The Series

IVDR Report Update 2025

Testing for NRG1 Fusions Series So Far

Exploring Inherited Cancer: from clinic to lab

IVDR Report Update 2024