[ARTICLE] Future classification of IVD instruments

The new Regulation 2017/746 on in vitro diagnostic devices (IVDR) will enter into force on May 26th, 2022. The IVDR introduces a rule-based risk IVD device classification system aligned with what is applied for medical devices. This system will replace the current classification system under the IVDD which classifies IVD devices based on pre-established lists and categories of products which in turn define the appropriate conformity assessment route to achieve market access.
 

The IVDR establishes four risk Classes A, B, C, and D with A being the lowest risk Class and D the highest, into which IVD devices will be classified taking into account the intended use of the device. The classification of devices into the different classes is determined by seven classification rules laid out in Annex VIII.
 

The possible conformity assessment pathways made available to manufacturers in order to market an IVD device and the level of requirements they entail are respectively determined by and proportionate to its risk classification.
 

Conformity assessment procedures for Risk B, C , and D Class IVD devices require verification and certification by a notified body, whereas only the conformity assessment for Class A IVD may be conducted without verification by a notified body to establish a declaration of conformity according article 17 for “placing on the market”.

The IVDR risk classes

A major consequence of the new classification system under the IVDR is that in contrast with the current system where most IVD devices currently on the market underwent conformity assessment without verification by a notified body, the majority of devices will fall in risk classes higher than A and therefore be subject to conformity assessment procedures outlined by annexes IX, X and XI, requiring the involvement of a notified body.
 

The question of whether an IVD device classifies in risk Class A is therefore an essential one as this will have important implications in terms of the resources needed to achieve market access.
 

The rule determining if a device classifies as a Class A device is classification rule 5, which states:
 

The following devices are classified as class A:

• (a) products for general laboratory use, accessories which possess no critical characteristics, buffer solutions, washing solutions, and general culture media and histological stains, intended by the manufacturer to make them suitable for in vitro diagnostic procedures relating to a specific examination;
• (b) instruments intended by the manufacturer specifically to be used for in vitro diagnostic procedures;
• (c) specimen receptacles

This classification rule leads to interpretation issues, among which is point (b) regarding the classification of instruments specifically intended by the manufacturer to be used for in vitro diagnostic procedures, hereafter termed IVD instruments.

The classification by default of all IVD instruments into Class A comes somewhat as surprising

The classification by default of all IVD instruments into Class A comes somewhat as surprising. In doing so, the regulators were likely considering the typical IVD analyzer used with an analyte-specific reagent or kit or device, for instance an ELISA plate reader. In this case, the instrument would classify as Class A and the reagents and kit would be classified in their own right, in Class B or higher.

Currently an increasing number of IVD instruments can provide diagnostic information on biological markers without using additional analyte-specific reagents

Nonetheless, currently an increasing number of IVD instruments can provide diagnostic information on biological markers without using additional analyte-specific reagents. Examples include instruments measuring blood gases or glucose via its sensors, automated hematology analyzers used to identify blood conditions such as thrombocytopenia or thalassemia, or devices performing refractometry on dried plasma spots for the detection of markers for multiple conditions such as cancer or neurodegenerative diseases.

How will some instruments be impacted by the IVDR?

A simplified interpretation of rule 5 would result in its classification into Class A, regardless of the intended use or risk the condition or pathology being tested represents for the wider population. It is nonetheless our understanding that as the classification of an IVD device is governed by its intended use (implementing rule 1.1), and that if several classification rules apply to the same device, the rule resulting in the higher classification shall apply (implementing rule 1.9), the IVD instrument will be classified according to its intended use by application of the most stringent applicable classification rule.

• If more than one intended uses are formulated for the instrument, it will be classified according to the intended use which results in its classification in the higher Class(implementing rule 1.8).

• If none of the other classification rules than rule 5 were to apply, for instance for instruments intended for the analyte-agnostic analysis of compounds in human specimens, the instrument would remain in Class A.

Thus, this appears to define two types of IVD instruments:

Those forming part of a system using additional analyte-specific reagents; and those with an independent measuring function which does not use any additional analyte-specific reagents.
 

In the first category the instrument would classify as Class A, and the additional reagents and kits would be classified in their own right. In the second, the instrument would be classified according to its intended use and the applicable classification rule resulting in the higher classification would apply.

It is therefore capital for IVD instrument manufacturers to carefully consider the intended use of their device to ascertain that no other classification rules apply

The risk of IVD instrument misclassification under the IVDR remains nonetheless elevated. We have observed that many IVD instrument manufacturers are planning to adopt a simplified yet convenient interpretation of classification rule 5 leading to the conclusion that their instrument is in Class A, and proceed to place their product on the market following the conformity assessment procedure using article 17 without involving a notified body. It is foreseeable however that number of the latter will face the unpleasant surprise of being informed, typically during a verification by the competent authorities, that their device in fact shall be classified in a higher risk class.
 

In such cases, the device would require to be withdrawn from the market until conformity with the requirements associated with the higher risk class can be verified and certified by notified body, which could undeniably lead to disastrous financial consequences for the manufacturer. It is therefore capital for IVD instrument manufacturers to carefully consider the intended use of their device to ascertain that no other classification rules apply before concluding that their device classifies as Class A under classification rule 5.
 

The MDCG is expected to issue guidance in due time that will hopefully clarify the application of classification rule 5.
 

How Medidee can help

Whether you are a manufacturer of an IVD instrument already on the market seeking to prepare the transition toward the new IVDR, or a manufacturer searching to place a new IVD instrument on the market under the new regulation, Medidee will assist you in formulating a suitable intended use, in determining the appropriate classification and conformity assessment pathway for your device, as well as in the planning and execution of the activities necessary to reach compliance with the requirements of the IVDR. Contact us now!

This article was written by Dr Jérôme Randall.