In Vitro Diagnostic Regulation (IVDR)
What is the IVDR?
If there’s one thing the worldwide COVID-19 crisis has taught us all, it’s that rapid, accurate diagnoses must be the rule rather than the exception in the life sciences industry. Such diagnoses are an essential component in today’s global healthcare system. They are obtained using in vitro diagnostic (IVD) devices — “in vitro”- pertaining to collecting and examining biological samples outside the human body.
In vitro diagnoses span a wide range of equipment and tests ranging from simple self-tests to detect pregnancy to complex laboratory diagnostics such as polymerase chain reaction (PCR) testing to diagnose genetic disorders and cancer. Considering the growing importance of in vitro diagnoses, the in vitro diagnostic regulation, or IVDR, was introduced to ensure high quality, outstanding results, and impeccable safety for the sake of all patients and doctors.
Understanding the Implications of IVDR for IVD Devices
The In Vitro Medical Devices Regulation (EU) 2017/746 (IVDR) is defined by the European Union as “the regulation [that] lays down rules concerning the placing on the market, making available on the market or putting into service of in vitro diagnostic medical devices for human use and accessories for such devices in the Union.” In other words, it serves as the European Union’s guiding regulation in specifying the safety, integrity, and quality requirements for any medical device with any in vitro diagnostic capacity.
Before 2017, the IVD Directive (IVDD) had defined the regulatory requirements for CE marking, indicating each device’s compliance. The IVDD, or 98/79/EC, came into force in 1998. This directive was expanded into the IVDR, introducing a harmonized regulation in the EU thanks to stricter rules governing the marketing of IVD devices.
The IVDR was published in May 2017 and took full effect on May 26, 2022. Subsequently, the IVDD will become wholly invalid at the end of the transitional period on May 26, 2027.
After this transition period, any company manufacturing or marketing IVD devices in or to EU countries will have to meet the requirements of this regulation which brings EU legislation into line with technical advances, changes in medical science, and changes in legislation. The IVDR has binding legal enforcement in all EU member states, and it sets higher standards for the quality and safety of IVD devices. Devices approved under the IVDR as suitable for operation in the EU market will be granted a CE mark by an EU Notified Body to demonstrate conformity.
Navigating the Transition Timeline from IVDD to IVDR for Different IVD Devices
The period within which IVD devices must transition to comply with the IVDR depends on the class of the respective device:
- Class A (non-sterile products) devices must have already been compliant; the deadline was May 26, 2022.
- Class A (sterile products) devices must be compliant by May 26, 2027.
- Class B must be compliant by May 26, 2027.
- Class C must be compliant by May 26, 2026.
- Class D must be compliant by May 26, 2025.
Defining IVD Devices and Their Uses
The category of IVD medical devices includes calibrators, instruments, reagent products, kits, receptacles, software, and systems. These devices are typically used to examine and analyze specimens to collect and provide information on the following aspects:
- Safety/compatibility of treatments
- Treatment response predictions
- Physiological or pathological status
- Monitoring of therapeutic measures
- Congenital physical or mental impairments
- Predisposition to medical conditions or disease
Most people have already been in direct or indirect contact with IVDs in one form or another, for pregnancy tests, blood tests, or, most recently, the ubiquitous COVID-19 tests.
IVDR Categories of IVD Devices
The IVDR organizes and divides IVD devices into four classes according to their potential risk during use:
- Class A includes all IVD devices that pose only a minimal risk when used. This class distinguishes between sterile and non-sterile products, as shown above. Cups for urine samples, for example, are categorized in this class.
- Class B includes all IVD devices that collect more critical measurements, such as a blood glucose meter. Misdiagnoses of such devices do not categorically pose life-threatening risks.
- Class C includes all IVD devices providing critical measured values. Misdiagnoses of such products can pose life-threatening risks. For example, therapy-accompanying diagnostics used in cancer treatment belong to this class.
- Class D includes all IVD devices that provide highly critical measured values, such as those used to determine infectious and fatal diseases. HIV tests are one example of an IVD device in this class.
In short, the higher the class, the higher the IVDR requirements are. A conformity assessment, including previous technical documentation, is sufficient for non-sterile Class A IVD devices at the lowest end of the bar.
The Impact of the IVDR on the Life Sciences Industry
Applying the IVDR is complex, and people in the life sciences industry should be aware of some changes that come with IVDR. Different assessment procedures are required depending on the risk class of the device. As far as medicinal products are concerned, it is mandatory to consult the respective regulatory authorities.
IVD Device Marketing in Europe: Key Concerns
As pointed out by MedTech Europe, the European trade association for medical technology, the IVDR poses many challenges and critical risks due to its incomplete infrastructure, which should be addressed sooner rather than later. Their recommended course of action entails the following:
- Ensuring both innovative and updated devices can be certified under the IVDR and reach patients and healthcare systems;
- Making the regulatory systems fully operational to certify the highest-risk IVD devices and companion diagnostics, including those needed to manage infectious diseases and diagnostics;
- Designating and building considerably more Notified Body capacity to support certification of all IVD devices and reduce the long and unpredictable certification timelines;
- Building additional system infrastructure needed to implement the IVDR, including requirements for performance studies, post-market, vigilance, and EUDAMED database, etc.
These remarks and concerns expressed by MedTech Europe carry weight, as they represent the collective voice of the medical technology industry, including diagnostics, medical devices, and digital health.
Hurdles in IVDR implementation
- Regulatory challenges
Notified Bodies are more frequently required to be engaged in CE marking. The IVDD specified that 90% of IVD devices could be self-certified. The IVDR stipulates that 85% of devices need a Notified Body to obtain CE marking. Only Class A non-sterile devices may continue to be self-certified. A Notified Body is an organization designated by a competent authority of an EU member state that performs conformity assessments to verify a product may be launched and made available to the market. More specifically, all devices previously allowed to be marketed must be classified and registered again, considering IVDR requirements, which presents a regulatory challenge and burden. It took around 12 months to fulfill a demand under the IVDD and achieve a CE marking for high-risk IVD devices. The IVDR makes the process of entering EU markets more time-consuming, increasing the overall application time.
An additional hurdle is that only a limited number of Notified Bodies meet the more stringent IVDR requirements and can therefore be engaged in the authorization process. The immediate consequence is that obtaining the CE marking and completing the process on time can take longer and prove more difficult. Experts who have gained the necessary knowledge, experience, and connections need to be guiding the marketers of IVD devices through this process.
- Innovation challenges
The highest-risk devices must meet the strictest requirements. These Class D devices are used to detect high-risk transmissible agents in blood, cellular matter, or tissue or to detect transmissible agents that cause life-threatening diseases like Ebola. The Medical Device Coordination Group (MDCG) oversees the harmonized implementation of t. It has issued a mandatory recommendation for Class D devices specifying that a Notified Body must call on an individual expert panel to verify the performance claimed by the device manufacturer. Moreover, these performance tests must be performed in EU reference laboratories.
It is essential to underline that high-risk devices need to go through this procedure only when they are the first of their kind. This status implies that no common specifications have previously been published in the EU Official Journal, and no certificate under the IVDD or IVDR has been granted for such devices. IVD devices are defined as the first of their kind when their intended purpose or their analysis technology is new to a market.
- Timeline challenges
As discussed above, the timeline for implementing the strict IVDR rules depends on the respective class of IVD devices. Manufacturers and marketers of such devices should start the transition periods as early as possible and meet the relevant deadlines for their products to comply with the IVDR. The capacity of Notified Bodies is limited, putting significant pressure on the industry.
Language Considerations for IVD Device Manufacturers and Marketers in the EU
The global clinical research organization, Precision For Medicine, recommends assessing gaps and prioritizing your products to meet complex clinical evidence requirements, update your supply chain control, and amend your IVD post-market surveillance and vigilance programs. You must also put these actions in perspective with the updates and improvements the IVDR brings to the market regarding submission, compliance, and control.
Overall, while the IVDR has undoubtedly brought some degree of harmonization to the regulatory stage in Europe, it has also introduced stricter regulations for IVD devices, and the industry needs to ensure that its products comply with the new requirements in time, while also factoring in appropriate localization for the EU market. Given the wide range of languages spoken across Europe, this can pose additional logistical hurdles.
Technical documentation and clinical research, labeling, manuals, instructions for use, and marketing copy—IVDR compliance means manufacturers and marketers of IVD devices need to speak the languages of their target markets regarding all these materials. This can be tricky to navigate without a dependable partner specialized not only in life sciences translation but also in the intricacies of IVDR regulatory compliance.
Vistatec can help. With our dedicated Life Sciences division and team of seasoned language experts from dozens of different life science disciplines, we work closely with some of the world’s leading organizations from the healthcare, medical device, clinical research, and pharmaceutical industries to provide everything from specific medical translations to full-scope, highest-quality localization solutions for devices and survey instruments. Vistatec is ready to assist IVD device manufacturers and marketers in navigating today’s complex regulatory frameworks with cost-effective, quality-assured localization processes so they can meet the requirements of IVD device labeling and translation. Contact our Life Sciences division today if you’d like to learn more about the benefits of partnering with Vistatec.