July 6, 2020

IVDR 2017/746 Implements Risk-Based Classification of IVDs that Focuses on Intended Use

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.

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June 30, 2020

Key Changes in the Regulatory Requirements for In Vitro Diagnostic Devices Marketed in the European Union Under IVDR 2017/746

Author: Suzanne Broussard

In vitro diagnostic (IVD) medical devices in the European Union are being held to a higher standard of scrutiny with the introduction of In Vitro Diagnostic Regulation (IVDR) 2017/746 by the European Commission (EC). 

Overview of In Vitro Diagnostic Regulation 2017/746  

The implementation of IVDR dramatically changes the regulatory landscape for IVD medical devices. Some of the biggest changes include an expanded definition of IVDs, a new classification of IVDs, the requirement of Unique Device Identification (UDI) on each device, an expansion of the Quality Management System, and the increased need for Notified Body (NB) review.  

The transition into IVDR is already underway. IVDs marketed in the EU will continue to require a CE Marking certificate to verify that the device meets all the regulatory requirements. Failure to meet the IVDR deadlines could be very costly to manufacturers that would either lose their CE Marking or fail to obtain one. The timeline below outlines the deadlines for manufacturers to become compliant with IVDR 2017/746. 

IVDR Timeline 

The IVDR is being implemented over a 5-year transition period in which it will fully replace the current In Vitro Diagnostic Directive (IVDD) 98/78/EC (Figure 1). IVDR 2017/746 was published May 5th, 2017, in the Official Journal of the European Union, and officially went in to affect May 25th, 2017; that means we are almost halfway through the transition period. During the transitional provisions, manufacturers can meet either IVDD or IVDR requirements. However, starting May 26, 2022, all new IVDs must go through IVDR. Some devices that lawfully obtained IVDD certificates have another 2-year grace period and may continue to be made available until May 27, 2025 (depending on serval factors). 

Article 110 Transitional provisions state that “Certificates issued by notified bodies in accordance with Directive 98/79/ED[EC] prior to 25 May 2017 shall become void by 27 May 2024.” IVDs that obtained certificates in accordance with IVDD prior to May 25, 2017 are valid until the end of the period indicated on the certificate, with some exceptions. Certificates issued under Directive 98/79/EC Annex VI become void at the latest May 27, 2024. If a device is lawfully placed on the market under IVDD prior to May 26, 2022 and placed on the market from May 26, 2022 by a certificate (refer to paragraph 2 and 4), the IVD can be on the market or put into service until May 27, 2025.  

See IVDR Article 110 and the IVDR Corrigendum number 8 for specific details. 

Starting May 26, 2024 IVDR will be full application, and all IVDs must be fully compliant.  

Figure 1. IVDR Timeline 

A screenshot of a cell phone Description automatically generated

It may seem that there is plenty of time to obtain IVDR compliance, but there are many hurdles to obtaining CE Marking under this new regulation. Also consider that there are major changes in almost every aspect regulation for medical devices in the EU, including MDR, MedDev2.7/1 rev.4, and CERs.   

Scope of IVDR 

The scope of IVDR is massive, and it impacts all aspects of in vitro diagnostic device manufacturing.  

  • The definition of an IVD is expanded to included software and companion diagnostics.  
  • This requires IVDs to use a new device classification system that will place 70%-80% of IVDs in a new category, and, thus, requiring significant work to obtain or maintain market approval.  
  • There is no grandfathering of any device. Even those currently on the market, must conform to the new IVDR standards. 

If you are marketing or intend to market any type of In Vitro Diagnostic Medical Device in the European Union, it is time to act. With the need for NBs substantially increasing, it is important to start the process of performing a Gap analysis and finding a NB.  

Let’s start by first looking at the newly expanded definition of IVDs under IVDR 2017/746.  

If you are marketing or intend to market any type of In Vitro Diagnostic Medical Device in the European Union, it is time to act. With the need for NBs substantially increasing, it is important to start the process of performing a Gap analysis and finding a NB.  

Let’s start by first looking at the newly expanded definition of IVDs under IVDR 2017/746.  

Definition of In Vitro Diagnostic Devices 

Section 1, Article 2 of IVDR 2017/746 expands the definition of IVDs. The addition of software and companion diagnostics to the definition of in vitro diagnostic devices significantly expands the definition of IVDs. Software is a medical device according to the definition of IVD if that is its intended purpose; thus, software as part of an instrument, software as a medical device, and apps are included in the definition of IVDs and fall under IVDR regulation. This includes genetic testing, companion diagnostics, as well as stand-alone software. 

The specific definition of In Vitro Diagnostic devices from IVDR 2017/746 is below. 

(2) ‘in vitro diagnostic medical device’ means any medical device which is a reagent, reagent product, calibrator, control material, kit, instrument, apparatus, piece of equipment, software or system, whether used alone or in combination, intended by the manufacturer to be used in vitro for the examination of specimens, including blood and tissue donations, derived from the human body, solely or principally for the purpose of providing information on one or more of the following: 

(a) concerning a physiological or pathological process or state; 

(b) concerning congenital physical or mental impairments; 

(c) concerning the predisposition to a medical condition or a disease; 

(d) to determine the safety and compatibility with potential recipients; 

(e) to predict treatment response or reactions; 

(f) to define or monitoring therapeutic measures. 

Specimen receptacles shall also be deemed to be in vitro diagnostic medical devices; 

Section 1, Article 1, 3. Defines what the IVDR does not apply to: 

  1. products for general laboratory use or research-use only products, unless such products, in view of their characteristics, are specifically intended by their manufacturer to be used for in vitro diagnostic examinations; 
  1. invasive sampling products or products which are directly applied to the human body for the purpose of obtaining a specimen; 
  1. internationally certified reference materials; 
  1. materials used for external quality assessment schemes.  

The next blogs in this series will cover the new Classification Rules.  

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.

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March 18, 2020

[FEATURED] EU’s IVDR Could Spell Disaster In Halting Spread Of Next COVID-19-Type Virus

The spread of COVID-19 has been slowed in many places through widespread testing of infected patients’ contacts. But the EU IVDR could mean the end of such early preventive action and much more rapid spread of such infections in future, unless action is taken now to amend the regulation.

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August 2, 2018

[FEATURED] Commission’s Draft EU Standardization Request May Overwhelm Tech Committees At 11th Hour

A great many EU medtech standards may not be ready in time for manufacturers to demonstrate compliance with the new regulations when they apply in 2020 and 2022. So, what is happening?

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May 4, 2018

[FEATURED] Does EU Regulation Of 3D-Printed Implants Expose Gap In MDR Regime?

“Given that 3D printing is used for making device implants, many would expect tight regulation. But the EU Medical Device Regulation does not specifically regulate it, and there may be easier routes to compliance than companies think, according to attorney Joerg Schickert.”

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