IVDR classification rules: Issues of interpretation

New requirements always raise issues of interpretation and the IVDR classification requirements are no exception. Below is a discussion of several key interpretative issues from the risk classification rules of the Regulation.

Section 1.10 of Annex VIII

This states: Each of the classification rules shall apply to first line assays, confirmatory assays and supplemental assays.

This is essentially a repeat of the principle stated in Section 1.7. ‘The manufacturer shall take into consideration all classification and implementation rules in order to establish the proper classification for the device’. It also reinforces the idea that all types of assays (first line, confirmatory and supplemental) must be classified in their own right. No definitions of these types of assays are given in the IVDR, but the message is clear in that they are all covered without distinction. If more than one rule applies, then the manufacturer must comply with the rule that results in the highest class (Section 1.8).

Rule 7

The meaning of ‘controls without a quantitative or qualitative assigned value’ in Rule 7 has been the subject of some discussion. This might be construed to include controls containing a specific analyte, such as a pathogen, but does not claim an assigned quantity or specific quality parameters. However, the presence of a specific analyte in the control material can itself be considered as a ‘qualitative’ assigned value. This latter interpretation would limit the definition materials giving a specific signal without containing the actual analyte.

Class A

Class A, as defined by classification Rule 5, is likely to be subject to debate, mainly because it is the only class that does not require the intervention of a notified body. Specific issues also arise from this rule.

Instruments

In placing instruments into Class A, the regulators probably had in mind the typical IVD analyser which, in order to produce results, has to work with reagent cartridges which are analyte/test specific. However, IVD instruments are being developed which can provide diagnostic information on biological markers without the use of any reagent at all.

For instance, refractometry on dried plasma spots provides diagnostic information. Such instruments are unlikely to remain in Class A. This type of instrumentation may emerge in a variety of diagnostic areas such as genetics and markers for cancer, Alzheimer’s disease, etc.

A good example of these analysers is the common haematology analyser used daily in thousands of laboratories to provide information on blood. They do not use any analyte-specific reagents. They use a saline-water-based solution which is used to dilute the blood sample taken from the patient. This sample diluent is not really a ‘reagent’ in itself. Is it sustainable to leave haematology analysers in Class A? Or will they migrate to Class B? A solution could be to consider the sample diluent as the ‘reagent’ (Class B) which could leave the instrument in class A. But this solution would only work for the haematology analysers and not for the spectroscopy instruments above which do not use any liquid.

General culture media

‘General culture media’ are covered under Rule 5 as Class A devices. However, they are not defined in the IVDR which may create confusion as to what is meant by this term. There is no commonly accepted definition of this term either. Instead there are several types of culture media (CM): preservation CM, enrichment CM, selective CM, differential CM, resuscitation CM, isolation CM, fermentation CM, etc.

‘General CM’ or ‘General Purpose CM’ can be defined as media that have multiple effects, i.e.: can be used as selective, differential or resuscitation media. Because of the variety of CM and their intended purposes, it may not be appropriate to have them all in Class A. For instance, CM for methicillin-resistant Staphylococcus aureus — an infectious agent — could be regarded as inherently presenting a higher risk than Class A because of the extremely high-risk micro-organism with which it is associated.

The concept in Rule 5 of general purpose products becoming IVD devices (including CM) if the manufacturer expresses an intent that they are made ‘suitable for in vitro diagnostic procedures relating to a specific examination’ is likely to create much discussion on aspects such as how the intent would be expressed to cross the threshold into the IVD world? What is the meaning of ‘specific examination?’ etc.

This is an excerpt from the BSI medical devices white paper: Explaining IVD classification issues. To browse our collection of medical device white papers, please visit the Insight page on the Compliance Navigator website.