IVDR is a separate regulation compared to the European medical devices regulation. However, it is closely associated with the regulatory authority.
The PIP breast implant scandal brought to light weaknesses in the overall regulatory process to control IVDs. That was back in 2017. As a result, it was decided that a new regulation for in vitro medical devices sector was in demand, and a plan to replace it by 2022 was brought up. Thus, to better align with international guidelines. As a result, the European Union’s IVDR 2017/746) replaces the previous IVDD 98/79/EC.
In contrast to the EU MDR, the scope of the IVDR includes diagnostic and monitoring devices that may attach to a person but are specifically used for monitoring human functions.
IVDs span from a blood collection tube or a pregnancy test, glucose & cholesterol tests, to a multipurpose analyzer intended for hospital laboratories.
How was the IVDR established?
So, in 2022 the long-running IVDD was replaced by another system called IVDR, thus inaugurating a new era for the regulations of diagnostic medical devices. Manufacturers aiming for the European market would now require CE labels and will face more stringent, more thorough EU regulations.
The IVDR replaced the IVDD on 26 May 2022 and was adopted by all European Union member states. The IVDR presents an enormous change to IVD Industry because, e.g., in terms of its change in the documentation and quality management system.
Around 2017, a majority of IVDs were self-certified. However, the IVD industry changed once the risk-based classification rules came, and greater notified body oversight with detailed regulatory guidance documents was enforced.
It is interesting to note that while the IVDR affects a smaller product range, it has a more extended implementation period.
Regulation (EU) 2017/746
Regulation 2017/746 (IVDR) was a Regulation of the European Union relating to the commercialization and the use of In vitro diagnostic medical devices. This regulation gives instructions on how to conform to in vitro device regulation.
Changes compared to IVDD included changes in device classifications, stricter inspection for manufacturers by Notified Bodies, the introduction of the Person responsible for regulatory compliance (PRRC), and many more.
When compared to IVDD, the industry faces significant challenges. These provisions have been revised. The regulatory department will scrutinize the respective documents more thoroughly.
Some significant changes to consider in the EU IVDR are discussed below.
The IVDR identifies four risk classes:
- The Class A (lowest risk)
- Class B
- Class C
- Class D
All purposes must be classified for devices with multiple intended purposes, and the highest risk class applies to the medical device in concern.
Class B, C, and D IVDs will require notified body involvement as a part of their conformity assessment.
Interestingly, the manufacturer is responsible for classifying a device, not the Notified Body or Competent Authority. However, following Article 47, if a manufacturer and Notified Body cannot agree on the classification, the Competent Authority will make the final determination.
Unlike the IVDD, the IVDR also encouraged a shift from the pre-approval stage (i.e., the path to CE Marking) to a life-cycle approach, having the specification documents related to the class of the device. In addition, more focus is given to clinical evidence.
Before implementing NBs, they must ensure compliance with their products. Only the lowest-risk classification (class A) doesn’t require NB intervention. The manufacturers have to implement systems for the protection of transparency.
The IVDR brought some concepts that were not previously applicable to In vitro medical devices, namely:
- Borderline and Classification issues,
- Authorized Representation,
- Performance Evaluation,
- Vigilance and Post-Market Performance Follow-Up.
As a result, more rigorous and appropriate surveillance by Notified Bodies has reduced the risks from unsafe devices and increased the scrutiny of Notified Bodies. The new EU regulations have put considerable strain on the notified body capacity.
Expanded Product Scope
Understanding the new vocabulary, knowing use, and indications of use in the scope of the IVDR are crucial first steps in achieving compliance. IVDRs include Genetic testing and diagnostic services, including stand-alone software, such as mobile medical apps, which may now be considered IVDs in line with the interpretation in MEDDEV 2.1/6.
The IVDR also introduces the concept of companion diagnostics, kits, and new rules for in-house tests.
Self-testing medical devices previously used in the “home environment” have been redefined as “to be used by laypersons.”
A test done by a patient will examine self-testing, regardless of the location. Now, self-testing devices and near-patient testing devices require to undergo a premarket approval approach.
Single-use devices willfully used during a single procedure that was part of the MDD have been introduced in the IVDR.
This information must be mentioned on the label, in the Instructions for Use (IFU), and in the registration information for the in vitro diagnostic medical device’s UDI. This affects user information and the registration of the device.
Companion diagnostics, essential for the safe and effective use of a medicinal product, must abide by the MDR’s general safety and performance requirements.
However, suppose the device is a single, non-reusable product, not intended to be used alone except in the given combination. In that case, the combination product is regulated under the medicinal product’s framework.
Also, if the medical device and the medicinal product are not physically related to each other, the device will be CE-marked.
The kit specifies a set of components packaged together and intended to perform a specific examination or part. This definition will help determine borderline cases where devices work together in an IVD procedure.
Greater Importance of Technical Documentation & Conformity assessment bodies
After the IVDR was introduced, manufacturers were now required to supply the appropriate Competent Authorities (CA) with all information necessary to show conformity.
Further authorizing them to share that information with patients or their representatives claiming compensation.
The manufacturer is required to provide full Disclosure of device details, including design, production, and quality testing.
The addition of a Person responsible for regulatory compliance was also new in IVDR. Due to this introduction, the non-European manufacturers were expected to face higher costs and more complex processes to enter the European market than their European counterparts.
Unique device identification (UDI)
A key addition to IVDR is the Unique device identification system. Unique device identifiers are markings that are unique to each device placed in the Eu market, provided by the manufacturer. The primary device identifier (Basic UDI-DI) must refer to an IVD’s Declaration of Conformity and on the certificates of Class B, C, and D devices. All registering device details should be searchable using the UDI number.
No grandfathering and continued surveillance
Regardless of prior approvals, recertification is mandatory for all currently approved in vitro diagnostic devices adhering to the new requirements.
Post Market Surveillance (PMS) and Post Market Clinical Follow-up (PMCF)
The IVDR introduces clinical evidence and post-market performance follow-ups as new concepts for IVDs. Performance evaluation is an ongoing process. That evaluates the device’s life cycle with clinical evidence to support the intended purpose.
It is in the solid post-market performance evaluation plan. It will ensure the identification of outdated and underperforming devices. This will help focus on new inventions and recent publications supporting the device technology.
The In vitro diagnostic regulation ivdr measures the validity of scientific, medical, and psychopharmacologic methods in three areas: scientific validity. Under IVDR, scientific validity has been introduced.
Analytical performance defines the ability of the device to detect and analyze a particular analyte, while clinical performance defines the device’s ability to yield results that correlate.
The analysis of performance but Article 56 provides the proposed contexts.
EuDAMED aims to develop an evaluation system focused on the IVD’s entire life cycle. For IVD, the manufacturer will address and notify the adverse effects of the EU competent authorities and submit regular updates on clinical effectiveness and risk management. Furthermore, it enforces the employment of better quality management systems from the manufacturer’s end.
Severe incidents that require repairs or replacements are also the responsibility of the manufacturer. If they find it significant, the report must address any member states in the EU concerned directly and make necessary updates.
IVDR puts a high emphasis on safety requirements. Therefore, manufacturers will state measures to eliminate or decrease the risks associated with using that equipment.
” A further requirement would include a description of where they have put into a practice safeguarding against noncomplicated hazards, and providing information to users on previously unexplained residual risks. “
It requires that the benefit of any medical device should outweigh any known and foreseeable risks resulting from its indicated usage and intended use.
The IVDR is quite similar to ISO 14971:2012 in that it lays greater emphasis on identifying risks such as foreseeable product misuse and mitigation.
There is a preference for design changes to eliminate hazards as far as possible (Design control). Follow state-of-the-art, and include proper communication of any residual risks to the user.
The benefit/risk ratio here implies controlling risks such that the benefits outweigh any remaining risks. Therefore, the IVDR recommends that Risk Management aligns with the Performance Evaluation.
What is technical documentation IVDR?
Following the IVDR, critical components of Technical Documentation that play quite a significant role in the conformity route are:
- Device Description and Specification
- Information Design and Manufacturing
- General Safety and Performance Requirements (GSPR)
- Benefit-Risk Analysis and Risk Management
- Product Verification and Validation
Full Disclosure on Medical Device Design, Production, and Quality Testing, beginning with an explanation of the device, its intended use, and technical specifications.
The technical documentation also covers more complex information, such as design and manufacturing details allowing readers to understand the intricacies of production, assembly, final product testing, and packaging.
Continuity on Performance Evaluation Reports (PER)
In contrast to the IVDD, the IVDR aims to bring a paradigm change by including an essential requirement to demonstrate.
- Labeling requirements,
- And the requirement for the Technical Documentation to contain adequate performance evaluation data.
The IVDR clarifies that the objective of Performance evaluation is to provide “clinical evidence” that supports the manufacturer’s intended use and not merely the analytical performance claims.
Verification & validation are fundamental requirements for the conformity of any IVD device. In the premarket phase, Performance evaluation represents a three-step process:
- Planning the evaluation,
- Collecting the clinical evidence based on data that shows the scientific validity and the analytical and clinical performance,
- Assessing and reporting on the data which has been collected, resulting in the PER.
Performance evaluation is now a life-cycle activity, with updates from scientific or medical practice and subsequent reassessments.
The Post Market Performance Follow-up (PMPF) is an essential element of Post Market Surveillance (PMS).
Post-Market Performance Follow-up (PMPF) Plan
According to Part B of the IVDR Annex XIII, Post-Market Performance Follow-up (PMPF) Plan is required for most in vitro diagnostic medical devices. This means the manufacturer must continuously review the PER to ensure it reflects the state of the art. Therefore, following the IVDR, every manufacturer must have a PMPF Plan and produce a PMPF Evaluation Report.
The IVDR details the new PMPF requirements, including the dependency on the type and classification of the device that needs to review; and how it should be defined. An organization’s quality management system is mainly responsible for ensuring the PMPF plan is followed.
What does the IVDR mean for the industry?
IVDR is leading to an entirely new infrastructure for innovation in the field of IVDs in the European Union. The IVDR ensures that Technical Documentation does not end with a submission. It requires updates throughout the device’s life cycle. Hence, it paves the way for a stricter quality management system.
The concept of legacy devices and methods of implementing regulation-related rules also has become relevant.
Several technical updated documents related to quality control and safety became a high priority to manufacturers after the IVDR was established. Manufacturers were also left without a choice but to have a quality management professional involved. They also needed to come up with and assign unique device identifiers to their in vitro diagnostic medical devices.