IVDR: the new era of diagnostic services

Background information on in vitro diagnostic services

Laboratory-based testing methods and medical devices play a critical role in diagnosis and medical decision-making. Indeed, different tests, equipment, and services can help patients and healthcare providers reach a diagnosis and identify the best clinical management plan. Therefore, in the field of medical diagnostics, patient safety and accuracy of tests, services, and results, is paramount.

There are two types of diagnostic techniques used in human healthcare –in vivo and in vitro. In vivo techniques are methods that are conducted in living organisms whereas in vitro techniques are conducted outside the body (1). Biopsies and imaging techniques such as X-rays, are examples of in vivo diagnostic tests, whereas blood tests and genetic testing are examples of in vitro diagnostics. Selecting between the two diagnostic methods depends on several factors such as the symptoms, the conditions, and the clinical status of the patient.

In vitro diagnostic devices (IVD) include any medical device used in medical diagnosis, such as reagents, kits, instruments, equipment, and software. It is therefore not surprising that strict regulations exist to help companies provide the best services that would benefit the patients. The European Union (EU) has established two major guidelines that govern the manufacturing and usage of IVD, the In Vitro Diagnostic Medical Devices Directive (IVDD) and In Vitro Diagnostic Regulation (IVDR) that ensure patient safety and accuracy.

IVDD and IVDR – what are they?

IVDD was introduced in 1998 and it was the initial set of guidelines for IVD in the EU. The IVDD took a list-based approach to assign risk classes with no clear indication of risk hierarchy. Instead, the regulatory classification was based on which conditions or pathogens a given medical device was designed to diagnose, grouping those conditions into different lists and annexes with each corresponding to varying levels of regulatory scrutiny and standards. Importantly, because IVDD was based on medical conditions already defined, it could not be effectively used for new emerging pathogens, creating the need for having diagnostic tests that could apply to a wider range of medical conditions.

IVDR is a more stringent set of regulations for IVDs in the EU and it replaces the IVDD guidelines. It determines the requirements for placing in vitro diagnostic medical devices on the market while ensuring the safety to patients as well as effectiveness of medical devices and tests. The new rule-based risk classification system focuses on each device’s intended purpose, and regulates the manufacturing, marketing, and the use of in vitro diagnostic medical devices, classifying them into risk categories (A-low risk to D-high risk).

Differences between IVDD and IVDR

Both IVDD and IVDR share some regulation processes, however, there are some key differences between them. For example, IVDR specifies comprehensive requirements for medical devices. Also, IVDR adds more requirements on risk management, device classification, reporting to authorities, and device traceability using unique device identifiers (UDI). In addition, IVDR requires ongoing monitoring of the device through post-market surveillance whereas IVDD is less strict. In general, under IVDD, the manufacturers can self-certify the majority of IVDs without the need for conformity assessment by a notified body. However, under IVDR the majority of the IVDs have to be assessed by a notified body for CE certification, and only a few devices can be self-certified (2).

Why the change to IVDR?

The shift from IVDD to IVDR reflects the evolving nature of medical technology as well as the EU’s commitment to providing IVDs with the highest standards that will be safe for the patients and have the best performance. Indeed the technological advancement of medical devices created the need for stricter controls in order to improve and monitor their safety and efficacy (2, 3).

The new landscape in medical diagnostics with IVDR

The European Parliament and the Council of the European Union adopted the regulation (EU) 2017/746 on IVDR on the 5th of April 2017, and it entered into force on the 26th of May 2017 (4). This year marked the initiation of a five-year period of transition from IVDD to IVDR. During this period manufacturers could apply for new certificates allowing a smooth transition from IVDD to IVDR whereas both IVDD and IVDR products can coexist (5). Initially, the transition period was until May 2022, however, due to a lack of notified body capacity as well as some disruptions that were caused by the COVID-19 pandemic, the European Commission extended the transitional period of IVDR implementation until the 26^th of May 2025. Therefore, companies can currently still have IVD classified products on the EU market but from May 2025 all manufacturers should comply with the updated regulations for IVDR. In addition depending on the device classification, manufacturers have until May 2028 to complete their transitions to IVDR (2).

What is the role and the purpose of IVDR?

The role of IVDR is to minimize the risk of potential differences in the IVDD that might occur in different EU countries (6). The regulations set by the EU ensure that the medical devices in the EU are safe and effective. Companies and health institutions are still encouraged to manufacture and develop their own products and devices that would benefit the patients, however, they should meet the new EU regulations for IVDR which aim to harmonize the conditions for in vitro testing in the EU (6).

Classification system for IVDR

IVDR applies to a range of medical devices that are used for diagnosis. Depending on the type of device, their potential risk for end-users as well as their intended purpose, they can be classified as Class A to D (2, 7).

Class A are devices that have low risk to the tested individual as well as the public health, such as:

• Specimen collection devices (swabs)
• General laboratory equipment (pipettes, test tubes)
• Basic software for data analysis

Class B are devices with moderate risk to the tested individual and/or low public health risk, such as:

• Self-tests for home use (pregnancy tests)
• Urine dipstick to determine urinary tract infection at point of care

Class C are devices with high risk to the tested individual and/or moderate public health risk, such as:

• Genetic tests for identifying specific mutations
• Microarrays for analyzing multiple genes or genetic markers
• Tests used for infectious diseases with moderate public risk

Class D are devices with a high risk to the tested individual and to the public, such as:

• Tests that determine donor compatibility for organ transplantation

A notified body must certify the in vitro medical devices before they are placed on the market. Class A non-sterile IVD devices can be self-certified without the involvement of a notified body (2). Devices used exclusively for research are exempt from IVDR (2).

The benefits to the patients

The EU regulations for IVDR not only serve as standards for manufacturers to comply with, but also have a significant impact on patients (4, 8). IVDR can benefit the patients in different ways including:

• Enhanced Safety and Performance

Medical devices are classified based on the potential risk. Therefore, the devices with the “higher risk” undergo stricter testings and validations before being available in the market for use by patients. In addition, manufacturers need to demonstrate high quality standards for the devices to minimize the risk of having a defective medical device, as well as monitor the device’s performance after it is on the market. All these measures increase the level of safety for patients who use IVDR products and services for diagnosis.

• Better and more reliable diagnosis

IVDR requires stricter performance monitoring for the devices. Therefore, they are more accurate, leading to a reliable diagnosis.

• Greater traceability

IVDR introduces the UDIs which trace the devices. This enables them to be recalled if necessary, ensuring patients receive the correct version of the device.

What are Medicover Genetics’ actions regarding IVDR certification?

Having patient safety and public health as the primary goal, our company is actively working on compliance with IVDR certification in the EU for our genetic testing products and services. This commitment ensures we continue to deliver a safe and reliable testing experience, maintaining our high standards and accurate results. Below are the steps we’ve taken so far towards IVDR:

• Early assessment of our genetic testing portfolio in order to identify needs for change and develop a comprehensive compliance plan
• Establishment of a dedicated, multidisciplinary team of experts in regulatory affairs, quality management, product development and clinical services who are leading our IVDR compliance plan
• Enhancement of our quality management system through reviews and evaluations, documentation control, risk management and post-market surveillance processes
• Collection of clinical validation data to demonstrate the safety and performance of our products
• Collaboration with notified bodies to ensure a smooth compliance process
• Communication and training of employees to raise awareness and ensure proper implementation of new procedures and standards

Conclusion

Although the IVDR primarily targets manufacturers, it ultimately serves to empower patients by ensuring they have access to safer, more reliable diagnostic tools for accurate diagnoses and informed healthcare decisions. Medicover Genetics is strategically and methodically working towards our IVDR certification to demonstrate our commitment to patient safety and public health, and to maintain our leading presence in the European market.

References

1. “What Are In Vitro Diagnostics and Why Are They Important?” BioMérieux Website, https://www.biomerieux.com/nl/en/blog/news-trends-diagnostics/what-are-in-vitro-diagnostics-and-why-are-they-important-.html. Accessed 19 Mar. 2024.

2. Bruun, Allan M. “What is EU IVDR? A Detailed Introduction (and the Role of eQMS).” SimplerQMS, 06 Mar. 2023, https://www.simplerqms.com/eu-ivdr/. Accessed 24  Mar. 2024.

3. Lubbers, Bart R, et al. “The New EU Regulation on In Vitro Diagnostic Medical Devices: Implications and Preparatory Actions for Diagnostic Laboratories.” HemaSphere vol. 5,5 e568. 21 Apr. 2021, doi:10.1097/HS9.0000000000000568, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061679/. Accessed 28 Mar. 2024.

4. “Regulation-2017/746-EN-Medical Device Regulation-EUR-Lex.” Eur-Lex.europa.eu, https://eur-lex.europa.eu/eli/reg/2017/746/oj. Accessed 28 Mar. 2024.

5. European Commission, Directorate-General for Internal Market, Industry, Entrepreneurship and SMEs. “Factsheet for manufacturers of in vitro diagnostic medical devices: medical devices change of legislation : what you need to know!” Publications Office of the European Union, 2018 https://data.europa.eu/doi/10.2873/971095. Accessed 06 Mar. 2024.

6. Kahles, Andy, et al. ““Structure and content of the EU-IVDR : Current status and implications for pathology.” “Struktur und Inhalt der EU-IVDR : Bestandsaufnahme und Implikationen für die Pathologie.” Pathologie (Heidelberg, Germany) vol. 44,Suppl 2 (2023): 73-85. doi:10.1007/s00292-022-01176-z, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9896441/. Accessed 19 Mar. 2024.

7. Directorate-General for Health and Food Safety. “Update – MDCG 2020-16 Rev.2 – Guidance on Classification Rules for in vitro Diagnostic Medical Devices under Regulation (EU) 2017/746 – February 2023” European Commission, 10 Feb. 2023, https://health.ec.europa.eu/latest-updates/update-mdcg-2020-16-rev2-guidance-classification-rules-vitro-diagnostic-medical-devices-under-2023-02-10_en. Accessed 19  Mar. 2024.

8. Dombrink, Isabel et al. “Critical Implications of IVDR for Innovation in Diagnostics: Input From the BioMed Alliance Diagnostics Task Force.” HemaSphere, vol. 6,6 e724. 20  May. 2022, doi:10.1097/HS9.0000000000000724, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126521/. Accessed 28 Mar. 2024.