Getting ready for In Vitro Diagnostic Regulation (IVDR)

While the pandemic continues to force many molecular diagnostics manufacturers and clinical laboratories to adapt their operations, the time is fast approaching when they will also need to comply with the new In Vitro Diagnostic Regulation (IVDR).

In this SelectScience^® webinar, now available to watch on demand, three leaders in the field of in vitro diagnostics share their insight on the new regulations: Sue Spencer, head of IVD and a principal consultant at Qserve, Erik Vollebregt, a founding partner of Axon Lawyers, Amsterdam, and Dr. Julien Senac, the global director of the IVD Focus Team at TÜV SÜD. Together, they provide everything you need to know in order to get ready for the transition to IVDR.

Think you’d benefit from this webinar but missed it? You can now watch it on demand at any time that suits you and read on for highlights from the live Q&A session.

You can also register free for part two: Commercial readiness in light of In Vitro Diagnostic Regulation (IVDR), which will run Wednesday, April 7, at 15:00 BST / 16:00 CEST / 07:00 PDT / 10:00 EDT

Q: My product has been on the market for 10 years, do I really need a performance evaluation plan?

SS: Yes, it's a requirement in the regulations. The plan is where you set out the specifications your product is to achieve and the data you have to support that. If it's an existing device, you may be looking back at data from other sources and saying that's what you're going to use. If there are any gaps you may need to do a study, but that's what you describe in your performance evaluation plan. It's like a V&V plan that you might have for FDA, but it’s a requirement.

Q: Should we conduct a performance evaluation on the prototype batch or the manufacturing batch?

SS: Your performance evaluation data should be representative of what you're expecting to see on the market. It needs to be conducted on a product that's been made in manufacturing conditions under SOPs. That doesn't mean it has to be full scale though. If you’ve made it to a smaller batch size, then as you scale up in the future, you need to validate that scale-up to show that it continues to be representative. That’s the key driver here, the data you're producing has to be representative of the final product.

Q: Can I use data from a 510(K)?

JS: Yes, you can use some of that data, but don't just think that because it was 510(K) approved, it will be enough. It’s very important to look at what data you have and get the statistics to support your claim. I would say that, depending on what we're looking for, especially with genetics, you need to be sure you have something representative of the European population, so case by case, that might not be sufficient data.

Q: If you have multiple distributors, who is the importer?

EV: The importer is defined as the first party placing the product on the market in the EU. Therefore, it would be the first distributor that imports the product. If you have several distributors that are each supplied from outside of the EU, theoretically, each of those distributors can be an importer. If you have a vertical supply chain, it's the first distributor in Europe.

Q: Can we think of intended purpose as similar to intended use under the FDA?

SS: If you were developing a new product today and you were going to sell it in Europe and the US, the more prescriptive today is Europe, however they're probably mutually compatible now. The discussion that you often hear is, are intended purpose and intended use the same? I think the consensus is they are, one is more of a US term, and one the official European term.

A problem we have in the IVD site is a lot of products are old, put together for the intended use 10 years ago with FDA, and that wasn't prescriptive. The bullet points I was stressing, you won't find in those intended use statements. You should be able to use an up-to-date FDA intended use statement, however, it needs to meet every single bullet point in the IVDR.

Q: My company develops infectious disease assays, which we provide on a platform made by a third party but marketed under our own name. We understand we are responsible for compliance, but they won't share their technical file. How can we CE Mark under IVDR?

EV: Dependent on how you want to market the product, there are several ways. For example, you could be a virtual manufacturer. However, it would be difficult if you don't have access to the technical file of the supplier because you will need to build your own technical files.

Another option would be to become a third-party brand distributor where you would brand the product with your own name, but the supplier is still labeled as the legal manufacturer. In that case, you don't need your own technical documentation, but you can market it under your brand name. The specific clause, Article 16, Section 1, Sub A in the IVDR provides for that.

Q: I am developing a Class C product to be launched on May 22, but my studies won’t be completed until October 2021. Will I still be able to get notified body approval if I apply at the end of 2021?

JS: Yes, you may get approval, but whether you have an approval by May 2022 will depend on different things.

If it’s a general Class C, the time required could be different. For a companion diagnostic test (CDx), for example, we could need consultation and that may take up to 120 days. That’s already four months in, so it could be very tight to get everything by May, knowing that you need the technical documentation, completed audit and the review by the notified body.

I would try to aim for the end of November 2021. That’s a safe bet because it gives us about six months before May and seems to be safe to have answered most issues.

Q: How do you demonstrate the scientific validity of an IVD instrument that is not intended for any specific analytes, for example, a mass spectrometer?

SS: Scientific validity is when you look at how the analyte compares to the clinical condition. There may be circumstances for things like wash buffers, accessories and non-instruments, where it isn't an analyte and there isn't a clinical condition. Particularly if you have an analyzer that is using multiple analytes, then that’s addressed as part of the technical files.

If you ask anybody “is scientific validity required?”, the answer is yes, unless duly justified, or those less frequent situations where it’s not applicable. But the notified body can't assume that, you must tell them why, and it must be a valid reason.

JS: I agree, essentially, it's a requirement. For an instrument, you justify that there is not one specific analyte. In that case, we have to see all the details, it might also be a Class A, so the notified body may not look at it at all. If your interest is in compliance, you may want to refer to the scientific validity of the other analytes in your technical documentation, so you have an idea of what your device could be used for or with.

SS: We also have to be careful that not all instruments are equal. Things like blood gas, for example, there are no reagents, so it's classified as Class C. You could potentially argue that scientific validity isn't applicable, but whether you call it scientific validity or whether you have to describe it as part of your performance evaluation plan, you will still have to explain why blood gases are related to the clinical conditions in your intended purpose. In that case, you probably still want to put scientific validity together. It’s really those low-risk instruments, the multi-use instruments and things such as wash buffers that would fall into this group.

Q: For general use IVD devices, where do you draw the line with marketing materials with regard to mentioning specific analytical targets?

EV: You draw it by what the intended purpose is, that's the whole idea of Article 7. As soon as you go outside the intended purpose, then you’re in tricky territory. The intended purpose needs to be reflected in all the documents that mention it, and marketing is one of them. It’s often hard for the marketing department to understand that the marketing materials under the IVDR are the public part of your technical documentation, and that's how I would advise to treat them.

SS: A top tip here is to make sure you train your marketing department.

EV: My perspective as a lawyer is that it happens so often, competitors call me, "Hey, look at this marketing material. This is their declaration of conformity. What can we do?" And then you see these marketing claims that widely diverge from the declaration of conformity-supported intended purpose, and then you make yourself one big target for a competitor to stick an enormous stick in the wheel of your marketing campaign.

Even spec sheets that you give to your marketing teams that visit customers, for example. You have a discussion between a customer and a sales rep, and the customer sends back an email saying, "Okay. So, I understand correctly that you told me that the device can do this and this and this." Then you can fall out of Article 7 because it's a record of the sales conversation.

Q: If we were to private label an IVD instrument, it appears we would have two options. First, we could privately label and then have an agreement with the OEM that they will meet and hold all IVDR requirements, freeing us from that responsibility, or we could private label, and if the manufacturer does not want to maintain responsibility, they would have to share their documents and data with us in order to meet IVDR requirements. Is this the correct line of thinking?

EV: Yes, because these are the only two options on the menu of the IVDR. There’s also the possibility to buy a technical file from an OEM that already has one but is not going to place it on the market themselves. They would just produce the device to your specifications, and you will be the manufacturer, but that's not normally how it works in a private-labeling scenario. For private labeling, it's either virtual manufacturing with access to the technical documentation of the other manufacturer or it is Article 16(1a).

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