On May 26th, 2017, the in vitro diagnostic regulation (IVDR) entered into force replacing the in vitro diagnostic directive (IVDD). However, the full application of the IVDR is taking place on May 26th, 2022. If that feels like a long way off, be warned, it most certainly isn’t!

Switching from IVDD to IVDR is a little like this… Until now, you have been making dinner for friends and family. You always make sure your food is good quality, otherwise you wouldn’t want to serve it to them. Your friends and family are quite happy with the results and give you feedback that you can continue working on your next meal. However, NOW you have been forcedly recruited to a Michelin 3-star restaurant. Either you take the job, or you’re not allowed to cook anymore. What you will be doing is, basically, still the same, but now there will be many more details to consider. There will be much more scrutiny on what you are doing and what you are producing, and you will have to prove the quality of your food to others several times before it even leaves the kitchen. The question is, do you think two and a half years is long enough to prepare yourself for becoming a 3-star Michelin chef?

The point is, of course, if you haven’t started to prepare for the switch to IVDR, then you really need to start now! If you’ve started, but things are kind of messy and slow, it’s also time to prepare a clear plan of action with SMART goals to close your gaps!

To start, let’s look at what has actually changed. Since the 1990s many regulations and standards have evolved to adapt a so-called risk-based approach. This means instead of rigid rules that apply to everyone equally, measures are decided proportionate to the risks posed to the public or other individuals. To be compliant, your company should, among other things, develop processes using this risk-based approach. For example, implementing control measures proportionate to the risk actions pose on quality and safety.

Risk classification

Under the IVDD, your company might have been allowed to self-declare conformity of your devices to obtain the CE mark as long as your diagnostic target was not listed in List A and B of the directive. It is estimated that approximately 80% of all IVDs were self-declared under the IVDD. Self-declaration provided less scrutiny and more autonomy to your company, but the IVDR might be changing things for you.

Instead of “listing”, the IVDR introduces 4 risk classes:

Class A Low individual risk and low public health risk

Class B Moderate individual risk and/or low public health risk

Class C High individual risk and/or moderate public health risk

Class D High individual risk and/or high public health risk

To determine the risk class of your device, you have to apply the following 7 classification rules:

As only class A devices are allowed to be CE marked through self-declaration, it is expected that only 20% of all IVDs will be self-declared under the IVDR.

Conformity Assessment

To obtain certification, your quality management system and technical documentation has to be assessed by a notified body, which will decide if the system and documentation is compliant with the requirements stated in the IVDR – i.e. with applicable standards, and/or with applicable common specifications. For Class C and D devices you have the option to undergo type examination and production quality assessment instead. With either route, you must provide samples to EU reference laboratories for batch verification of your class D devices. If your device can be categorized as sterile, near patient testing, self-testing or companion diagnostic, you need to be aware of additional requirements in the IVDR.

GSPR and clinical performance

While working under the IVDD you will have made yourself familiar with the essential requirements, which have been replaced by the General Safety and Performance Requirements (GSPR) under the IVDR. Don’t worry, the requirements are similar, but you will find there is greater detail and, most probably, you will need to add to your documentation to be compliant.

More detail and more specific information are common themes when comparing the IVDR to the IVDD. Another example is what you must provide for your performance evaluation, i.e. the clinical evidence that comprises scientific validity, analytical performance and clinical performance. Scientific validity refers to proving the relation between the analyte and the condition to be analysed (proof of concept). Analytical performance refers to proving the ability of your device to identify and measure the analyte correctly (analytical sensitivity & specificity, interferences, etc.). Finally, clinical performance refers to proving your device’s ability to correctly differentiate between healthy and affected population (PPV & NPV, diagnostic sensitivity & specificity, etc.). Attention! Clinical performance studies in a clinical environment are mandatory. You might not have the required data available, so it is time to close the gaps!

Post-market

Post-market surveillance has also received an update and you will have to make yourself comfortable with UDIs, EUDAMED, more stringent incident and trend reporting, Post-Market Follow up… and more. By the way, do you have your Post-Market Surveillance Report ready for your class A and B devices? And how about the Periodic Safety Update Report for your class C and D devices? So much to do, so little time!

Challenges and timelines

As if identifying and closing your gaps isn’t challenging enough, you will also have to be patient with the authorities. As of August 2019, EUDAMED is not yet ready, no notified bodies are designated for the IVDR so far, the EU reference laboratories are not set up, and common specifications have not yet been published.

What’s more, there will be fewer notified bodies designated for the IVDR than there have been for the IVDD, despite expected demand being a tenfold increase! However, don’t imagine you will be able to use this as an excuse for not having started. If your device was self-declared under the IVDD, but will require notified body certification under IVDR, you must be as ready as possible by May 26th, 2022. On the other hand, if your device is certified by a notified body under IVDD, you have a little more time to breath…

Judith Kairies
Judith KairiesRegulatory Affairs Consultant & IVDR specialist
Tel. +46 (0)72 5668797

Flexible & responsive support

At Plantvision we understand the challenges you are facing. We offer a range of services that can be customized to your company’s needs:

• Advice on the application of standards
• Internal audits
• Gap analyses
• Transition plan from IVDD to IVDR
• Updating your quality management system
• RA support during transition process (QA/RA Partner service)
• Workshops, courses and customized training

Contact me to find out more about how we can help your organization achieve compliance excellence!