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Outside the Lab Quality assurance and quality control, Regulation and standards

Supporting Laboratories Through the IVDR Transition

sponsored by Thermo Fisher Scientific

The new EU legislation for in vitro diagnostic (IVD) medical devices, In Vitro Diagnostic Regulation (IVDR) (EU) 2017/746, is currently scheduled to go into effect in May of 2022 after a five-year transition period. The new regulations aim to improve the quality, safety, and reliability of IVDs in countries requiring CE-IVD compliant products. These products will be reassessed according to level of risk; the majority will require review and approval by a notified body. Manufacturers and suppliers of IVDs will be obligated to provide analytical performance data, scientific validity, peer-reviewed literature, and clinical performance data to show that their products meet these new, more stringent standards for clinical evidence.

Thermo Fisher Scientific has made significant investments to ensure that its CE-IVD products will meet the new requirements. In this article, Nicola Normanno (Director of Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, Naples, Italy, and President of the International Quality Network for Pathology) and Garret Hampton (President of Clinical Next-Generation Sequencing and Oncology, Thermo Fisher Scientific) discuss the steps the company has taken to prepare for the IVDR transition – and what clinical laboratories must do to ensure they are ready.

GH: How ready are EU clinical laboratories for the new regulations? 
NN: Unfortunately, most labs are not prepared for IVDR. They are counting on having IVDR-ready solutions available from their partners and don’t realize that many test companies have been slow to start the necessary validation to achieve compliance. Additionally, many labs involved in clinical practice believe they can continue to use the panels available based on their current regulatory labeling and don’t realize they will be required to provide additional validation.

Although the date for IVDR implementation is widely known, there has not been enough communication to help labs prepare. As a result, most labs are unclear on the implications and what they should be doing to get ready for the new regulations. This gap in preparedness is going to create a huge problem in the European diagnostics world in the next few months.

Garret Hampton.

GH: How will the new IVDR requirements impact patient care? 
NN: Generally speaking, the introduction of additional guidelines to reduce variation and increase oversight of in vitro diagnostics is a good thing for patient care. Manufacturers and developers must provide clinical and analytical validation of new tests and external bodies verify that companies’ claims are accurate.

Currently, there is little oversight in this market, so the new regulations will improve our ability to provide high-quality biomarker tests. However, we need to be sure labs can focus their attention on achieving compliance to avoid a gap in accessing this testing once IVDR goes into effect.

GH: What is the role of the International Quality Network for Pathology in supporting clinical labs in complying with new IVDR requirements? 
NN: IQN Path will play an essential role in the implementation and maintenance of IVD regulations in the next few years. Every member of IQN Path is involved in external quality assessment (EQA) or quality market testing. We do not certify labs; when there is a new biomarker, our group looks at the technology to help harmonize the approach from different EQA providers.

EQA will be increasingly important to identify gaps in the process or performance of these tests.

EQA will play an important role supporting post-market surveillance of in vitro test performance to make sure the technology isn’t failing after IVDR compliance is secured. In some cases, this post-market surveillance has identified areas that need additional focus or innovation before the product is fully compliant in real-world settings. IQN Path will also help guide academic labs that want to continue to use laboratory-developed tests or commercially available solutions designated as “research use only” in clinical research. In these cases, labs will need to provide additional information on clinical and analytical validation. EQA will be increasingly important to identify gaps in the process or performance of these tests.

GH: How do you see new IVDR requirements impacting EQA programs in the EU? 
NN: To accelerate validation of devices and tests, academic labs and companies developing these technologies will need to collaborate closely. Companies and manufacturers will need to provide additional clinical and analytical validation, which will be difficult without ready access to patient samples and data from lab partners. As new devices are jointly validated by academia and industry, other clinical labs can trust this data knowing it came from their peers at the bench, not just device makers looking to secure approval.

NN: As a manufacturer and distributor of medical devices, how is Thermo Fisher preparing its NGS solutions to meet the new IVDR requirements? 
GH: Thermo Fisher is committed to assisting our customers through this transition by assuring them that our CE-IVD products are prepared to meet IVDR compliance. As president of clinical NGS and oncology, I have been focused on ensuring our NGS instruments will meet the new requirements. We began our preparation for the IVDR transition several years ago with the design and development of our Genexus platform; it was developed under IVDR design controls and, for existing customers, a future field service update will update the sequencer to full compliance and eliminate the need for the purchase of another IVD-labeled instrument. 

For our NGS platforms and assays, Thermo Fisher has invested heavily in our manufacturing facilities to ensure that these products are manufactured and tested with the quality and documentation requirements needed to be compliant to the new regulations in the future.

Nicola Normanno.

NN: Can you expand on the clinical evidence that a manufacturer like Thermo Fisher must demonstrate to support the intended use of your NGS instruments? 
H: The new regulations require manufacturers and suppliers to ensure that their products meet more stringent standards for clinical evidence. As such, we’ve made significant investments to demonstrate the clinical utility of our NGS solutions.

There are two primary pillars to our approach in demonstrating this clinical evidence for our oncology applications. The first is developing solutions that can detect and report relevant biomarkers, such as EGFR mutations and ALK fusions, that are widely used in the clinical field and supported by medical guidelines. The second pillar will leverage our pharmaceutical partnerships to demonstrate the assays’ clinical utility as companion diagnostics (CDx) to support targeted therapy selection. Thermo Fisher also embarked on a multimillion-dollar program to collect clinical-grade samples for testing and development to support the clinical validation needed for IVDR.

NN: Which NGS products are you preparing to meet the new requirements? 
GH: Our primary NGS platform that will be fully IVD compliant is the Ion Torrent Genexus Integrated Sequencer. This is a first-in-class, highly automated, fully integrated NGS sequencer capable of generating results in as little as 24 hours. 

To complement the Genexus sequencer, we will also have a fully compliant automated platform, the Ion Torrent Genexus Purification System, to facilitate the extraction and quantification of nucleic acids directly from clinical samples. The Genexus Purification System links directly to the Genexus sequencer, allowing full sample-to-result processing with only two touchpoints and less than 20 minutes of hands-on time.

To support clinical oncology applications, we will also launch a CE-IVD labelled 50-gene solid tumor diagnostic test to run on the Genexus System, Oncomine Dx Express Test, which will dramatically improve oncology patient care by providing complete actionable precision medicine results in as little as 24 hours. We also plan to ensure that the 46- gene solid tumor Oncomine Dx Target Test will be compliant under IVDR.

For reproductive health applications, we are planning to release the Ion Reporter Aneuploidy Dx as a fully IVD-compliant workflow for preimplantation genetic testing for aneuploidy (PGT-A) on the Ion GeneStudio System. The Ion Reporter offers rapid, simple workflows to support aneuploidy detection using as little as a single cell’s DNA as input.

Thermo Fisher is committed to delivering additional clinically validated assays that will operate on the Genexus System in the future. These assays include comprehensive genomic profiling, hemato-oncology, and reproductive health applications.

Would you welcome the proposed extension of the transition period? 
NN: I think that an extension of the transition period is definitely needed. However, I feel that we need clear and defined plans from government bodies , companies , and laboratories to ensure that the new system will be in place at the end of the transition. Even in the initial transition period, we only began discussing the new IVDR a few months before the deadline. GH: It would not change our plans; we will carry on with our work at full speed. 

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