Classification of in-vitro diagnostic medical devices under the IVDR

The new IVDR (Regulation (EU) 2017/746) has introduced a risk-based classification system for in-vitro diagnostic medical devices (IVDs), analogous to that of non-IVDs, that did not exist under the former EU Directive 98/79/EC (IVDD). IVD classification determines the level of complexity of the conformity assessment for CE-marking under the IVDR. And the transitional periods for “legacy” IVDs are based on such new classification. If you are not fully aware on how IVDs are to be classified under the IVDR, read on.

Key takeaways:

• Manufacturers should not assume that self-declared IVDs under the former Directive 98/79/EC (IVDD) correspond to low-risk classification under the IVDR. They should always verify the classification from scratch.
• Accessories for IVDs and IVD kits must be classified in their own right.
• All definitions, implementing rules and classification rules in IVDR Annex VIII must be considered for the determination of the correct device class, considering also guidance document MDCG 2020-16.

Content:

What does IVD classification mean? What classes exist?

The new Regulation (EU) No. 2017/746 on in-vitro diagnostic medical devices (IVDR) has introduced a classification system for IVDs, analogous to the classification system for non-IVDs, which is driven by the intended purpose and inherent risk of the device. 

Classification is the action of determining which IVDR class applies to a given IVD, and this is incumbent on the manufacturer.

Just like for non-IVDs under the EU MDR, the IVDR has established 4 class levels, in increasing order of risk for individuals and public health, namely:

• Class A – low individual and public health risk
• Class B – moderate individual risk, low public health risk
• Class C – high individual risk, moderate public health risk
• Class D – high individual and public health risk

Logically, IVDs intended to test for life-threatening conditions fall under Class D, whereas IVDs intended to test for non-vital aspects fall under Class B, which can be viewed as the default class for all IVD tests that are not specifically covered in higher classes. No IVD tests fall under Class A, which is basically only applicable to laboratory equipment and tools in support of IVD testing.

How do I classify an IVD?

To classify the medical device, manufacturers need to consult Annex VIII of the IVDR, consisting of two chapters:

• IMPLEMENTING RULES, providing generic instructions on how to apply the rules.
• CLASSIFICATION RULES, encompassing only 7 rules, summarized in the table below.

Contrary to the EU MDR, IVDR Annex VIII does not include definitions to guide the classification. Whiles some important terms (e.g. “specimen”, “companion diagnostic”, or “kit”) are defined in Article 2 of the IVDR, other relevant definitions can only be located  in guidance document MDCG 2020-16, and should be always considered to avoid incorrect interpretation of important terms like “first-line device”, “detecting the presence of”, or “devices for screening”.

Manufacturers should follow the below steps to classify their IVDs:

1. Evaluate each definition in IVDR Article 2 and MDCT 2020-16 rev.2, for applicability to the device in question.
2. Take all implementing rules in chapter 1 of IVDR Annex VIII into account. Implementing rules provide general guidance to the classification process. For example, if several rules or sub-rules apply, the strictest rule and sub-rule shall be applied.
3. Check all classification rules in chapter 2 of IVDR Annex VIII, whether they are applicable to your IVD or not. As the intended purpose is the basis for applying the classification rules, it is essential to be as precise as possible, a small difference of the wording can make a big difference from a regulatory viewpoint.

The extensive and useful guidance document MDCG 2020-16 discusses details on how to interpret and apply Annex VIII and also brings examples. It should always be used alongside Annex VIII when classifying a device.

In addition, beware of Team-NB’s Position Paper on the classification of SARS-Cov-2 tests. According to the IVDR and MDCG 2020-16, IVDs for SARS-CoV-2 testing fall under the highest risk class, i.e. Class D, per Rule 1 in IVDR Annex VIII. Team-NB considers that the current level of risks associated with COVID, which are lower than during the pandemic, warrants a reclassification of such IVDs and recommends a reclassification as Class C, per Rule 3c, and even a potential further reclassification to Class B, per Rule 6, once more data on the post-pandemic phase becomes available, especially regarding the long COVID syndrome. This Team-NB position paper is expected to trigger a review of MDCG 2020-16.

How are accessories classified?

Per IVDR Article 2(4) an accessory to an IVD is legally defined as:

“an article which, whilst not being itself an in vitro diagnostic medical device, is intended by its manufacturer to be used together with one or several particular in vitro diagnostic medical device(s) to specifically enable the in vitro diagnostic medical device(s) to be used in accordance with its/their intended purpose(s) or to specifically and directly assist the medical functionality of the in vitro diagnostic medical device(s) in terms of its/their intended purpose(s);”

Before classifying your device, it is important that you determine whether a given item that you consider a component to your IVD test may fall under this legal definition. 

Accessories to IVDs are classified separately from the device (i.e. “in their own right”, as stated in implementing rule 1.3 in IVDR Annex VIII).

Conversely, and also in accordance with the implementing rules in IVDR Annex VIII:

• Calibrators intended to be used with a given IVD fall in the same class as the corresponding IVD.
• Control materials with quantitative or qualitative assigned values for either a specific analyte or multiple analytes, fall in the same class as the corresponding IVD.

In brief, when classifying IVDs that are used in combination, implementing rules are essential to determine the appropriate classification approach.

In the EU, IVDs are classified according to their risk and divided into classes A, B, C, and D.

How is IVD software classified?

In consideration of implementing rule 1.4 in IVDR Annex VIII, software classification depends on whether it is:

• Software that drives a device or influences the use of a device, in which case it shall fall in the same class as the device. For example, software that drives an enzyme immunoassay analyzer would be classified as the corresponding instrument that falls in Class A, per classification rule 5(b).

Software that is independent of any other device, in which case it shall be classified in its own right. This corresponds to medical device software (MDSW) as described in guidance document MDCG 2019-11 on the qualification and classification of software.

There is no specific classification rule for software in IVDR Annex VIII, and the intended purpose becomes the only driver in the determination of the most appropriate class. A few examples, however, are provided in guidance document MDCG 2020-16:

• MDSW intended for high-resolution analysis of HLA sequencing data, for transplantation purposes would correspond to Class C, per Rule 2.
• MDSW intended to generate estimated glomerular filtration rate (eGFR) or albumin creatinine ratio (ACR) for staging acute kidney injury (AKI), or an enhanced liver fibrosis (ELF) score which correlates to the level of fibrosis, or a model for end stage liver disease (MELD) score, would fall under Class C, per Rule 3(g).

For MDSW intended for aggregation and analysis of results from various IVDs, this would be considered a combination of devices (i.e. between the MDSW and the various IVDs). According to implementing rule 1.9 in IVDR Annex VIII, “if several classification rules apply to the same device, the rule resulting in the higher classification shall apply.”

For more details, see our blog article on Medical device software (MDSW) under the EU MDR and IVDR.

What if I struggle with the classification?

The manufacturer is always responsible for the correct classification of his IVDs. However, classification can be tricky and manufacturers can only apply their best judgment to the determination of the applicable class after relying on the official regulatory references.

As mentioned earlier, the Medical Device Coordination Group (MDCG) has issued 2 important guidance documents to help manufacturers with IVDR classification:

• MDCG 2020-16, Guidance on the classification of IVDs.
• MDCG 2019-11, Qualification and classification of MDSW, under the EU MDR and IVDR.

If these guidance documents do not suffice, manufacturers can send an official inquiry to the concerned competent authority (i.e. in the Member State where the manufacturer or its EU Authorised Representative has its registered place of business). When the IVD might require the involvement of a Notified Body for the conformity assessment process, the manufacturer can also discuss the selected classification with its Notified Body.

In case of a dispute between the manufacturer and its Notified Body, the competent authority will – after consulting the MDCG – decide on the classification and inform the MDCG and the commission about the decision. The competent authority will base its decision upon the classification rules given in Annex VIII of the IVDR, new scientific evidence, and/or any information which becomes available in the course of the vigilance and market surveillance activities, as defined in Article 47 of the IVDR.

The manufacturer is always responsible for the correct classification of his IVDs.

Be mindful of the fact that there could be situations where the classification turns out to be convoluted due to an incorrect qualification of the product as an IVD. In such cases, the manufacturer should answer the following questions carefully:

• Does my product qualify as a medical device at all?
• Is my device a medical device or an in-vitro diagnostic device?
• Is my product an IVD or just general laboratory equipment? Or is it rather for research use only (RUO)?

For qualification support, note that MDCG has issued a Manual on borderline and classification (current version 3 – September 2023), which is intended to progressively grow with specific examples on difficult qualification and classification cases.

To learn more about the qualification of medical devices and borderline issues, read our blog article Is my product a medical device in Europe? How to determine if your product requires medical device CE marking.

How do classification rules apply to kits?

The IVDR regulates not only IVDs, but also kits, which are defined as.

“a set of components that are packaged together and intended to be used to perform a specific in vitro diagnostic examination, or a part thereof.”
[IVDR, Art. 2(11)]

Kits are included in the definition of IVD. Consequently, a Kit needs to be CE-marked under the IVDR and the entity placing the IVD Kit on the market becomes an IVD manufacturer. The manufacturer must then classify the IVD Kit following the exact same process and classification rules as for any IVD.

For example:

• A kit for isolation and purification of nucleic acids from human specimens that contains various reagents and solutions, is in itself a Class A device under IVDR classification Rule 5(a). 
• A self-test kit for the detection of SARS-CoV-2 that contains a swab for specimen sampling, a reagent and the antigen rapid test, is in itself a Class D device under the IVDR classification Rule 1, second indent.

The components in an IVD Kit might include non-IVD medical devices or non-device components. And some of the non-device components may correspond to “accessories for IVDs”, as defined in IVDR Art. 2(4), if they specifically enable the IVDs to be used in accordance with its/their intended purposes.

Where do I document the classification rationale?

The technical documentation to be compiled by the manufacturer as evidence of conformity needs to include the device’s risk class as well as the  justification for the classification rule applied as part of the device description chapter [IVDR, Annex II, section 1.1(f)].

It is good practice to present the justification in the form of a table, where the 7 classification rules in Annex VIII of the IVDR are listed, and the justification for applicability or non-applicability is indicated for each of them. This shows to the Notified Body or competent authority who might review the documentation, that the manufacturer understands the classification process and has thoroughly applied it. In our consultancy practice, we recommend to do so even when the exclusion of a given classification rule seems obvious for the type of IVD, e.g. companion diagnostic classification rules in the case of a pregnancy self-test.

How Decomplix can help

As you now know, the specifics and the intended use of an IVD are essential for the correct classification under the IVDR. Are there specific questions you would like to discuss? Please do not hesitate to contact us.

Are you wondering whether the risk classification under the IVDR coincides with the risk classes in the USA?  Find more information in our bespoke article on Medical device regulatory strategy – US vs. EU.

We are happy to support you (re-)defining your intended purpose, confirming the qualification of your product as IVD, or classifying your IVD under the IVDR. Learn more about our services.

Further reading

• Is my product a medical device in Europe? How to determine if your product requires medical device CE marking
• The intended purpose – or what does your medical device do?
• Medical device software (MDSW) under the EU MDR and IVDR
• CE marking for in vitro diagnostic devices under the IVDR
• Medical device risk classification under the EU MDR: 8 things you need to know