Author: Suzanne Broussard
The new In Vitro Diagnostic Regulation (IVDR) 2017/746 brings significant changes to the regulation of In Vitro Diagnostic (IVD) devices in the European Union (EU). One of the biggest changes is the use of risk-based classes for IVDs that require significant clinical support and regulatory oversight, and the deadlines for compliance are looming as the IVDR transition period ends on May 25, 2022.
The switch to IVDR will have an enormous impact on the requirements to obtain a CE Marking. Under current European Union regulations, only 10% to 20% of IVDs sold under the In Vitro Diagnostic Directive (IVDD) require Notified Body (NB) assessment. This flips with under IVDRs new risk-based classification system, and an estimated 70% to 80% of IVDs will requiring Notified Body (NB) review.
The new IVDR 2017/746 classification of IVDs is based on an internationally recognized risk-based classification system that places IVD devices in four classes (A-D) based on the intended use of the device, which ultimately determines the risk to both the patient and the general population. Class designation is determined using 10 implementing rules and 7 classification rules.
Classification: Risk-Based Class Designation is Determined Using 7 Classification Rules
IVDR classes are based on globally accepted criteria developed by the Global Harmonization Task Force (GHTF) in February 2011 (GHTF evolved into what is now known as the International Medical Device Regulators Forum [IMDRF]). The risk classes are A through D; class A devices have the least risk, and class D devices have the most risk. This risk-based classification is replacing the list-based classification of the IVDD 98/78/EC and will result in the vast majority of IVDs being up-classified.
Let’s look directly at the IVDR regulation’s seven Classification Rules that are outlined in Annex VIII of IVDR 2017/746. These rules first define each class and are explained in each class below. The rules start identifying devices that have the most risk to both the patient and population (Class D) and then continue with criteria for IVDs that pose less risk. Correctly determining the device classification is critical as the class dictates the level of clinical support and documentation required and the need for NB review. It is important to understand that the classification is based on the devices intended purpose, and thus the risk to the patient and population.
Class D devices have a high risk to the patient and a high risk to public health, and therefore must meet the highest level of conformity. Rule 1.
Class D devices are governed by Rule 1 under Classification Rule 2.1. They include devices that detect the presence of, or exposure to, transmissible agents, life-threatening transmissible agents, and infectious disease with a high risk of propagation.
Class C devices have a high risk to the patient and/or medium risk to public health, and are defined in Rules 2, 3, 4.
The IVD devices in class C according to Rule 2 are intended to be used for blood grouping or tissue typing, blood components, cells, tissues or organs intended for transfusion or transplantation, with some exceptions explicitly stated.
Devices in class C according to Rule 3 are intended to be used for infectious agents without a high risk of propagation, pre-natal screening, companion diagnostics, monitoring levels of medicinal products, detecting congenital disorders in embryos, foetus, or new-born babies; and genetic testing.
Rule 4 further defines class C devices as those that are intended for self-testing “except for devices for the detection of pregnancy for fertility testing and for determining cholesterol level, and devices for the detection of glucose, erythrocytes, leucocytes and bacteria in urine, which are classified as class B.
Class B devices have moderate individual patient risk and/or low public health risk. Class B devices are defined under Rule 4 and 7; class B is also the default class for devices that do not fall within the scope of any stated rules (Rule 6).
Class B devices are less risky than class C devices and include the self-testing devices that are exempt from class C in Rule 4 (see class C above), such as those used to detect glucose. Rule 7 states that “Devices which are controls without a quantitative or qualitative assigned value are classified as class B.”
Class A devices have a low risk to the patient and low public health risk
Under Classification Rules 2.5 Rule 5, the following devices are classified as Class 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;
- instruments intended by the manufacturer specifically to be used for in vitro diagnostic procedures;
- specimen receptacles.
Under the new classification rules, it is estimated that the vast majority of IVDs will be class B or class C. When classifying an IVD, it is important to first look at the implementing rules, 1.1 to 1.10 of the Classification Rules. As you can see below, the implementing rules provide manufacturers with additional information as to which class the device is categorized, especially in regard to combination products and multiple-use devices.
Implementing Rules (Annex VIII)
1.1 Application of the classification rules shall be governed by the intended purpose of the devices.
1.2 If the device in question is intended to be used in combination with another device, the classification rules shall apply separately to each of the devices.
1.3 Accessories for an in vitro diagnostic medical device shall be classified in their own right separately from the device with which they are used.
1.4 Software, which drives a device or influences the use of a device, shall fall within the same class as the device. If the software is independent of any other device, it shall be classified in its own right.
1.5 Calibrators intended to be used with a device shall be classified in the same class as the device.
1.6 Control materials with quantitative or qualitative assigned values intended for one specific analyte or multiple analytes shall be classified in the same class as the device.
1.7 The manufacturer shall take into consideration all classification and implementation rules in order to establish the proper classification of the device.
1.8 Where a manufacturer states multiple intended purposes for a device, and as a result the device falls into more than one class, it shall be classified in the higher class.
1.9 If several classification rules apply to the same device, the rule resulting in the higher classification shall apply.
1.10 Each of the classification rules shall apply to first line assays, confirmatory assays, and supplemental assays.
It is projected that the vast majority of IVDs will fall into class B or class C. Many devices currently on the market will be reclassified into a higher risk based on the IVDR classification and, thus, require significant investment from the manufacturer to remain regulatory compliant. All devices that fall in Class B, C, and D have conformity assessment procedures that require NB assessment, as do some class A devices that require sterilization.
Our next blog will cover Analytical and Clinical Technical Documentation for IVDR 2017/746 Compliance and Software as Part of IVDR. Also, check out to the first post in this series.
Please reach out to us with any questions or to find out how we can help your organization transition to compliance with IVDR 2017/746.