Notified Body capacity for In Vitro Diagnostics

Arguably the biggest change in the IVDR is the introduction of a risk-based approach to classification in combination with increased Notified Body oversight.

The In Vitro Diagnostic Medical Devices Regulation (IVDR)^[1] governs the placing on the market, making available on the market and putting into service of in vitro diagnostic medical devices (IVDs) for human use and their accessories in the European Union.  The IVDR replaces the In Vitro Diagnostic Medical Device Directive^[2] (IVDD).

IVDs can be described as:

• reagents or reagent products
• calibrators
• control materials
• kits
• instruments, apparatus or pieces of equipment
• software or systems

whether used alone or in combination and that are intended to be used in vitro for the examination of specimens derived from the human body, including blood and tissue donations, to provide information on:

a)    a physiological or pathological process or state

b)    a congenital physical or mental impairment

c)     a predisposition to a medical condition or a disease

d)    safety and compatibility with potential recipients, for example of blood transfusions of organ transplants

e)    a prediction of treatment response or reactions

f)     defining or monitoring of therapy

Specimen receptacles are also considered to be IVDs but may not be if they are not intended specifically for the purpose of IVD examination^[3].

Many of the changes introduced in the IVDR mirror those in its sister legislation the Medical Devices Regulation (MDR)^[4]. Arguably the biggest change in the IVDR is the introduction of a risk-based approach to classification in combination with increased Notified Body (NB) oversight. Like the MDR, the IVDR has a set of rules for classification and applies the level of third-party oversight in conformity assessment in relation to the perceived risk associated with the product. The changes in the system of classification of IVDs according to risk are significant compared to the IVDD. The IVDD used a list-based system, with specific product types being identified in two lists (lists A and B) in an annex to the Directive. The majority of IVDs were not included in these two lists and therefore did not require third-party, i.e. NB, involvement in conformity assessment.

In contrast, the IVDR identifies four risk classes based on their risk profiles: Class A (lowest risk), Class B, Class C, and Class D (highest risk).  Classifying IVDs requires use of seven rules, and the rule leading to the highest risk class will apply. For devices with multiple intended purposes, all purposes must be classified, and the highest risk class is applicable. Class B, C, and D IVDs will require certification by a Notified Body NB involvement as part of their conformity assessment. Only the lowest classification class A devices do not need NB involvement with the exception of Class A devices that are sterile. This change in classification system, will mean that many more devices will require the involvement of an NB. Many manufacturers will, for the first time, need to work with an NB. There is anecdotal evidence that there will be a shift from 10-20% of IVDs being NB certified to 80-90%.

NBs need to be designated against the scope of activities that they will perform.  The NBs that are designated for any particular European legislation are listed in the New Approach Notified and Designated Organisations Information System – called NANDO. As of February 2020, there are only three NBs designated for the IVDR – BSI in the UK and the Netherlands, and DEKRA in Germany.

The IVDR entered into force on 25 May 2017 and applies from 26 May 2022. This provides for a five-year transition period. The transition period for the IVDR was set as two years more than the MDR because of the extent of the changes and the new requirements introduced by the IVDR including the classification system, and the resultant need for increased NB capacity. However, three years into the transition period, and with only two years of the transition period left, there are only these three NBs designated for the IVDR.

The transitional provisions for the IVDR are set out in Article 110 of the regulation. This includes a provision that certificates issued by NBs in accordance with IVDD after 25 May 2017 become void by 27 May 2024. However, as mentioned above, this may only apply to 10-20% of devices on the market. This gives an additional two-year period for products with existing NB certificates, but there can be no significant changes in the design and intended purpose of the device in that period. Additionally, the requirements of the IVDR on registration of economic operators and of devices, post-market surveillance, market surveillance and vigilance apply, even for devices making use of this extended grace period. However, IVDs that are self-certified under the IVDD will not have CE certificates and so are currently unable to take advantage of this additional two-year period. As a result, May 2022 becomes their hard deadline.

Experience with designation of NBs under the MDR showed that a number of designations were made in the final months of the transition period. While it is possible that will also happen in the case of the IVDR as well, this will not provide enough time for manufacturers who do not currently have a relationship with a NB to make the necessary arrangements. Manufacturers who will need the involvement of a NB for conformity assessment to the IVDR should identify their chosen partner as soon as possible, if they have not done so already. The options are either one of the organizations that are already designated, or to look at the list of NBs for the IVDD listed in NANDO and check which ones are progressing with designation to the IVDR. Whichever NB you decide to work with, check the scope of their designation or intended designation covers all your devices.

Author: Eamonn Hoxey, of E V Hoxey Ltd, UK, is a writer, trainer and consultant on a range of life science areas including regulatory compliance, quality management, sterility assurance and standards development