At the same time as the EU MDR (2017/745) came into force, so the EU IVDR (2017/746) also superseded the old IVD directive, which had become unfit for purpose due to significant advances in technologies and within the Medical Device industry. The EU IVDR came fully into force in 2017 and introduced a significantly more stringent regulatory environment for in vitro diagnostic medical devices.
The IVDR covers equipment (including receptacles) intended by the manufacturer to be used to 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 e.g. concerning a physiological or pathological process or state, on the predisposition to a medical condition or disease, the safety and compatibility of a process with potential recipients or to predict treatment response or reaction.
The In Vitro Diagnostic Medical Devices (IVD) Regulation (2017/745) was enacted to provide for an updated harmonised regulatory environment for all in vitro diagnostic medical (IVD) devices sold within the European Economic Area. All products which fall within the scope of the Regulation must meet certain essential safety and administrative requirements and are to be CE marked to show that they comply. Such products may then be freely sold throughout Europe. CE marked products may also be placed on the UK-market until June 2024.
The IVD Directive defines an IVD device as ”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;
This definition needs to be read in conjunction with the definition of a medical device in the Medical Devices Regulation in order to get a full description of the scope of the Regulation.
Excluded from the Regulation are invasive sampling devices that are directly applied to the skin in order to obtain a specimen, and general laboratory apparatus or research-only specific equipment that is not intended for use, by design, for in vitro diagnoses. Devices for performance evaluation of IVD devices are not IVD devices but manufacturers must prepare documentation to be available for inspection by the Competent Authority.
Like the Medical Devices Regulation (EU MDR), the IVDR includes provisions for all relevant hazards, including mechanical and electrical safety and provisions for electromagnetic compatibility. Devices which fall within the scope of the IVDR are, as with the MDR excluded from the scope of the other Directives and Regulations. However, equipment which may have an application which is not exclusively medical will usually have to comply with the other Directives too for instances where it is used outside of a medical context.
Examples of IVD Devices
- Laboratory centrifuge, blood composition analyzer.
- Personal use OTC devices: blood sugar monitors, pregnancy testers.
- Specimen receptacles and other accessories to an IVD device are also considered as IVD devices.
The Regulation applies different administrative requirements to devices depending on the risk which they present to the user. These have been significantly updated from the previous IVDD to be more in line with those of the EU MDR, where classification is based on the risk associated with a device and the seven classification rules are detailed in Annex VIII of the UVDR.
There are four classifications, D through A, with D being the highest risk:
- Class D covers -threatening conditions and transmissible agents in blood and biological materials intended to be transplanted or re-administered into the body. It also covers blood grouping or tissue typing in some instances.
- Class C relates to high-risk IVD devices including situations where the diagnosis relates to life-threatening conditions and situations, e.g. cancer and highly infectious diseases It also covers self-testing devices although some exceptions exist.
- Class B is the ‘catch-all’ category for devices (including pregnancy and fertility tests) that are not covered other classifications. Note that this is a significant change from the previous IVDD classification and means that most IVD devices will require notified body involvement.
- Class A covers items such as laboratory instruments, receptacles and devices.
General Safety and Performance Requirements
The ‘manufacturer’ (or authorised representative, as the legal entity in Europe) must ensure that the device meets the General Safety and Performance requirements specified in Annex I of the Regulation and follow the appropriate conformity assessment procedure, as detailed within the body of the regulation, which will depend on the type of device, route to market and manufacturer processes and systems.
The requirements include (amongst others):
- a general requirement for safe design through risk management
- the minimisation of risks from contamination
- compatibility with materials with which they are likely to come into contact
- the minimisation of hazards of infection and microbial contamination
- provision of sufficient accuracy
- protection against radiation
- adequate product marking
- adequate user instructions
Many of the details of these essential requirements are laid out in a series of Standards for Product Safety which have been (or are being) developed to meet the requirements of the Regulations
Manufacturers (or their agents) must typically:
- comply with the general safety and performance requirements of Annex I of the Directive
- demonstrate design verification
- maintain a risk management system
- demonstrate clinical evidence of the effectiveness of the device
- implement a procedure for post-market surveillance
- complete a Declaration of Conformity
- maintain a file of technical information about the product
- put the CE mark on the product (or its packaging)
- obtain the involvement of an EU Notified Body where required (All Sterile, Class B, C & D Devices)
- Maintain the services of a suitably qualified person responsible for regulatory compliance.
- Maintain a unique identification (UDI) system for their devices
Conformity assessment methods are similar to those of the MDR - being largely quality system based however it is expected that 80% of IVD Devices will require notified body involvement as only non-sterile Category A devices are exempt from this requirement. This is a significant change from the IVDD process.
Where self-certification is accepted, the manufacturer must compile a technical file which is available for inspection upon request by the Competent Authority, along with Risk Management, Quality Management and post-market surveillance plans and reporting processes.
Notified body assessments may include; limited testing/inspections appropriate to the device, a full quality system audit for Production or Product Quality assurance, or alternatively, an EC Type examination of the device together with a production quality system and final product/batch verification.
One of the provisions which distinguishes the Medical Device Directives from the other New Approach Directives is that they establish standing committees to consider the development and application of standards produced in support of the essential requirements, and to consider (in effect) 'matters arising' regarding the safety of devices within the scope of the Directives.
As part of this process of consideration, a formal post-market surveillance, or vigilance plan and reporting procedure is required by the Regulation, through which manufacturers, health professionals and others must report certain problems which arise in the use of medical devices and in clinical trials. This vigilance system is administered by the competent authority in each of the member states, and requires each manufacturer to have a procedure in place for post market surveillance and reporting of adverse incidents.
The Directive came into force in May 2017, and all in vitro diagnostic medical devices manufactured and placed on the market after that date must comply. A transition period for full implementation, lasting five years, expired in 2022. At the current time, all IVDs on the market will require a new and complete conformity assessment by 2027 (depending on their risk classification), although this has already been extended once.
All devices for sale in the EU must be registered through the EUDAMED database, administered by the EU Directorate General for Health and Food Safety.
The MHRA also have a very useful website including lots of helpful publications to download.