The transition from IVDD to IVDR: Key Differences and Changes

As the regulatory landscape for in vitro diagnostic devices (IVDs) in Europe evolves, manufacturers and stakeholders must navigate the significant shift from the In Vitro Diagnostic Medical Devices Directive (IVDD) to the In Vitro Diagnostic Medical Devices Regulation (IVDR). This transition introduces significantly stricter requirements, greater oversight, and increased responsibilities for all players involved. Here, we break down the key aspects of this transition and what manufacturers need to consider to ensure compliance under the IVDR.

 Key takeaways

  • Missed transition for self-declared IVDs: Many IVDs that were previously self-declared now require compliance under Class A of the IVDR, with the transition deadline having passed in May 2022. Manufacturers must urgently address any gaps to meet these requirements.
  • Insufficient technical documentation: The fragmented evidence once sufficient under the IVDD no longer meets IVDR standards. A complete, well-structured technical file with robust clinical data is now mandatory.
  • Notified Body oversight underestimated: Devices requiring Notified Body involvement, including Class A products with sterile or measuring functions, are often overlooked. Early engagement with a Notified Body is essential to avoid certification delays.

Content

What’s driving the transition to the IVDR?

Regulation (EU) 2017/746 (IVDR) was introduced to address the outdated nature of the former Directive 98/79/EEC (IVDD), which had been in place for nearly two decades.

The rapid advancements in diagnostic technologies and the need for more robust regulations led to the development of the IVDR. It aims to enhance patient safety, improve device traceability, and ensure that IVDs on the market are both safe and effective for their intended use.

IVDD vs IVDR – What is the difference in classification?

IVDD

Under the IVDD, devices were grouped primarily into List A and List B (Annex II),  and  self-declared devices:

  • Annex II, List A: Devices with the highest risk, such as those for detecting HIV or Hepatitis.
  • Annex II, List B: Moderate-risk devices, such as tests for rubella or blood glucose.
  • Self-testing devices: Covered specific devices intended for home use, like pregnancy tests.

Most devices not listed in Annex II were self-declared by the manufacturer, with minimal external oversight. 

IVDR

The IVDR has introduced a risk-based classification system that aligns more closely with the risk-based approach seen in the Medical Device Regulation (EU MDR). This new system classifies IVDs into four classes (A, B, C, and D) based on the potential risk they pose to patients and public health:

  • Class A: Low-risk devices, such as laboratory instruments and reagents without a critical role in medical diagnosis. Class A devices can often still be self-declared unless they are sterile.
  • Class B: Moderate-risk devices, including many self-testing devices that were previously self-declared under IVDD. These now require Notified Body involvement under the IVDR.
  • Class C: Higher-risk devices, such as tests for infectious diseases and companion diagnostics. These devices are critical to diagnosing serious conditions but not as high-risk as Class D devices.
  • Class D: Devices posing the highest risk to patients and public health, such as blood screening tests for transfusions and HIV or Hepatitis tests. These require the most stringent level of review, including involvement from EU reference laboratories (EURL).
A technical device - in-vitro-diagnostic. A close-up of a microscope in the medical field.

In the EU, IVDs are classified according to their risk and divided into classes A, B, C, and D.

The IVDR classification system uses seven rules (compared to the IVDD’s list-based approach) to determine the risk class of an IVD based on its intended purpose and inherent risks. These rules consider factors such as:

  • The criticality of the diagnostic information provided by the device (e.g., devices that detect life-threatening conditions like cancer or HIV are classified as Class D),
  • Whether the device is used for self-testing,
  • Whether the device is intended for use near the patient or in a laboratory setting.

What are the consequences of the reclassification of IVDs?

For manufacturers, the shift from the IVDD to the IVDR’s classification system has several major consequences:

  • Increased Regulatory Oversight
    Notified Body involvement is mandatory for most devices, including those that were previously self-declared under the IVDD. This means longer lead times for approval and increased costs due to more rigorous conformity assessments.
  • Need for More Clinical Evidence
    Devices in Classes C and D require extensive clinical performance data to demonstrate safety and efficacy, which must be reviewed by Notified Bodies.
  • Impact on Legacy Devices
    Many devices that were previously self-declared must now undergo Notified Body scrutiny. MDCG 2020-6 provides guidance on how to handle clinical evidence for these legacy devices. 

MDCG 2020-16 offers detailed guidance on the classification rules for IVDs under the IVDR. It outlines how manufacturers should classify their devices based on factors like the intended purpose, the level of public health impact, and the potential risks associated with diagnostic errors.

What are the implications of the transition for Notified Body involvement?

With the transition to the IVDR, the landscape of IVD certification has undergone a fundamental change. One of the most significant shifts is the dramatic increase in Notified Body involvement. Under the IVDR, it is estimated that more than 80% of IVDs will now require Notified Body oversight, compared to only 20% under IVDD.

This shift is driven by the IVDR’s new risk-based classification system, which places stricter regulatory controls on higher-risk devices, ensuring that devices with a greater potential impact on public health undergo a conformity assessment process.

Many legacy devices that were previously self-declared must now undergo a conformity assessment.

Notified Bodies under the IVDR will take on a far more active role in ensuring that manufacturers comply with the more stringent regulatory requirements. The core responsibilities of Notified Bodies include:

  • Conformity assessment
    Conducting in-depth conformity assessments for devices falling under risk Classes B, C, and D, which cover moderate- to high-risk IVDs. This assessment involves reviewing the technical documentation, clinical performance evaluation, and post-market surveillance plans.
  • Evaluation of clinical evidence
    Notified Bodies must scrutinize the clinical evidence provided by manufacturers to ensure that devices meet the applicable General Safety and Performance Requirements (GSPR) in IVDR Annex I. This includes reviewing clinical performance studies, scientific validity, and the overall benefit-risk ratio of the device.
  • Audits and on-site inspections
    As part of the conformity assessment, Notified Bodies will perform regular audits and inspections of manufacturing sites to verify compliance with quality management systems and ensure ongoing product safety.

For devices transitioning from IVDD to IVDR, Notified Bodies play a critical role in ensuring that manufacturers meet the new regulatory requirements. Many legacy devices that were previously self-declared must now undergo a conformity assessment.

Moreover, Notified Bodies are required to ensure that post-market surveillance systems are in place and functioning effectively. The new IVDR framework places an emphasis on continuous monitoring, meaning manufacturers must work closely with Notified Bodies to update safety and performance evaluations even after the device has been placed on the market.

How to prepare for Notified Body Oversight?

To mitigate potential delays and challenges, manufacturers should:

  • Engage Early
    Begin discussions with Notified Bodies early in the development process to clarify requirements and ensure adequate time for conformity assessments.
  • Prepare Comprehensive Documentation
    Ensure that all technical documentation, clinical performance data, and quality management systems are fully aligned with IVDR requirements.
  • Develop a Long-Term Regulatory Strategy
    Post-market surveillance and vigilance reporting must be integrated into a long-term strategy, with Notified Bodies regularly reviewing performance data.

MDCG 2019-6 presents questions and answers on requirements relating to Notified Bodies under the EU MDR and IVDR.

What are the challenges for Manufacturers?

The move from self-certification to mandatory Notified Body involvement affects a wide range of devices, especially those that:

  • Are newly classified into higher-risk classes (B, C, or D),
  • Were previously self-declared under IVDD but now require a conformity assessment under the IVDR,
  • Are classified as self-testing devices or companion diagnostics, which require more rigorous performance evaluations.

Only a small subset of Class A devices (low-risk, non-sterile) will be eligible for self-certification by manufacturers.

The significant increase in the number of IVDs requiring Notified Body oversight brings several challenges:

  • Limited Availability of Notified Bodies
    As the demand for Notified Body services rises, manufacturers face challenges in securing assessments in a timely manner. The limited number of Notified Bodies designated under IVDR has created bottlenecks, with some manufacturers struggling to find an accredited body with the necessary expertise to evaluate their devices. Manufacturers must now engage early with a designated Notified Body, as limited availability could lead to significant delays in market access.
  • Longer Review Times
    With Notified Bodies involved in reviewing a greater volume of devices, lead times for market approval have increased. Manufacturers need to factor in these extended timelines when planning product launches or transitioning existing devices from IVDD to IVDR.
  • Increased Costs
    The shift from self-certification to mandatory third-party review has increased costs for manufacturers. Notified Body assessments, regular audits, and clinical evaluations contribute to higher compliance expenses. 

MDCG 2022-14 emphasizes the importance of early engagement with Notified Bodies to avoid delays and potential market disruptions, especially for manufacturers of high-risk IVDs that are crucial for public health.

What about clinical evidence requirements?

One of the most significant shifts in the IVDR is the heightened emphasis on clinical evidence. Unlike its predecessor, the IVDD, which often allowed manufacturers to bring devices to market without extensive clinical data, the IVDR mandates that manufacturers provide robust, detailed clinical evidence to support the safety, performance, and scientific validity of their devices. This shift is designed to improve patient safety and ensure that devices on the market deliver accurate and reliable results.

One of the most significant shifts in the IVDR is the heightened emphasis on clinical evidence.

Clinical evidence for IVDs is established through the collection of data as a result of a performance evaluation, which covers the assessment of scientific validity data, analytical performance data, and, when applicable, clinical performance data. This requires not only generating new evidence for devices already on the market but also maintaining continuous post-market clinical follow-up (PMCF) for high-risk devices. And this applies to all IVD classes and types, including the low-risk, Class A IVDs, as well as medical device software (MDSW).

MDCG 2022-2 provides guidance on general principles of clinical evidence for IVDs.

Key components of clinical evidence under the IVDR

Analytical Performance refers to the ability of an IVD to accurately detect or measure the intended analyte under specified conditions. It assesses key parameters such as:

  • Sensitivity
    The ability of the device to detect low levels of the analyte (limit of detection).
  • Specificity
    The ability to correctly identify the target analyte without cross-reactivity with other substances.
  • Precision
    Consistency in obtaining similar results under the same conditions.
  • Accuracy
    How closely the test result matches a reference standard.
  • Reproducibility
    The device’s ability to provide consistent results across different laboratories, operators, or conditions.

To demonstrate analytical performance, manufacturers must provide comprehensive data from laboratory-based studies, bench tests, and comparisons with reference methods (e.g., gold standards). This data is critical to ensure that the device can perform reliably before entering the clinical setting. According to the IVDR (Article 56 and Annex II), the documentation of analytical performance is essential in the technical documentation.

Clinical performance relates to how well the IVD’s ability to provide clinically useful results that can aid in diagnosis, monitoring, or management of a disease or medical condition in the intended population. This performance must be demonstrated through clinical data obtained from:

  • Clinical performance studies
    These studies involve testing the IVD in real-world clinical settings to evaluate its efficacy and effectiveness on human samples.
  • Post-market surveillance (PMS)
    After the IVD is on the market, continuous monitoring and collection of clinical data are necessary to ensure ongoing compliance with performance standards.

The IVDR mandates that clinical performance data must be sufficient to demonstrate that the device performs effectively within its clinical context, providing accurate and clinically relevant results for the intended use. Clinical performance is critical because it provides evidence that the IVD will yield meaningful information in patient care. According to the IVDR (Art. 56 and Annex II) Clinical performance data are a vital part of the clinical evidence used to support the CE. 

Scientific validity refers to the association between the analyte detected or measured by the IVD and the specific clinical condition or physiological state. Manufacturers must demonstrate that the analyte is relevant to the condition they claim the device is used for. For example, a diagnostic test for a particular disease must prove that the biomarker being measured is scientifically valid as a marker for that disease.

How does IVDR’s focus on clinical evidence affect manufacturers?

The IVDR’s focus on clinical evidence encompasses several key changes that impact manufacturers:

  • Post-Market Clinical Follow-Up (PMCF)
    Manufacturers are required to conduct ongoing PMCF activities to continuously monitor the performance and safety of their IVDs after they have been placed on the market. This ensures that any issues or deviations in performance are quickly identified and addressed.
  • Legacy Devices
    For devices already on the market under the IVDD (so-called “legacy devices“), manufacturers must reassess their clinical data and may need to generate new evidence to meet the higher standards of the IVDR. 
  • Increased burden of proof
    Manufacturers must now invest significantly more resources into generating, collecting, and documenting clinical evidence. This involves conducting clinical performance studies and ensuring ongoing post-market clinical follow-up activities.
  • Notified Body scrutiny
    Clinical evidence will be closely scrutinized by Notified Bodies, particularly for higher-risk devices. Manufacturers should engage with Notified Bodies early to ensure that their evidence meets the required standards.
  • Transitioning legacy devices
    Legacy devices that were certified under the IVDD will need to be re-evaluated to ensure they meet the IVDR’s more stringent clinical evidence requirements. This may require generating new clinical data or conducting additional performance studies. For details on how to ensure a smooth transition, see section What can manufacturers do to ensure a compliant transition from IVDD to IVDR?
Two men and a woman standing around a table writing on a paper

The level of clinical evidence required under the IVDR is directly linked to the device’s classification.

Which economic operators are affected by the transition to the IVDR?

The IVDR introduces strict requirements for economic operators, which include manufacturers, authorized representatives, importers, and distributors. Each has an essential role in ensuring product safety and regulatory compliance. 

Manufacturers

Manufacturers hold the primary responsibility for ensuring that devices comply with the IVDR. This includes:

  • Conformity Assessment
    They must conduct or arrange for conformity assessments through Notified Bodies for devices classified in higher-risk classes (B-D).
  • Technical Documentation
    Comprehensive technical documentation must be prepared and maintained for each device. This includes details about device design, risk management, clinical evidence, and post-market surveillance (PMS) systems.
  • UDI and Device Registration
    They must implement a Unique Device Identification (UDI) system and register devices in the European database (EUDAMED) for traceability.
  • Post-Market Surveillance (PMS) and Vigilance
    Manufacturers must set up a PMS system to monitor device performance and safety post-market. They are responsible for reporting incidents and field safety corrective actions (FSCA) to competent authorities.  

EU Authorized Representatives (EC-REP)

EU Authorized representatives (EC-REP) act on behalf of non-EEA manufacturers to ensure that devices placed on the market comply with the IVDR requirements. Their key duties include:

  • Keeping Technical Documentation
    EC-REPs must have access to the technical documentation and provide it to authorities upon request.
  • Registration
    They are responsible for registering devices and themselves in EUDAMED.
  • Regulatory Interface
    EC-REPs are the main contact for competent authorities and must cooperate with them during audits and inspections.
  • Liability
    Under the IVDR, EC-REPs share liability with the manufacturer for defective devices. 

Importers

Importers play a vital role in verifying that products entering the EU market meet the IVDR requirements. Their responsibilities include:

  • Verification of Compliance
    Importers must check that devices have CE marking, a valid Declaration of Conformity, and are registered in EUDAMED. They also need to ensure that labeling complies with IVDR standards.
  • Record-Keeping
    They are required to keep records of device suppliers and customers to assist in traceability.
  • Storage and Transportation
    Importers must ensure that devices are stored and transported under appropriate conditions to maintain device quality and safety.
  • Post-Market Surveillance and Vigilance
    Importers are required to inform manufacturers, authorized representatives, and competent authorities of any safety concerns or non-compliances.

Read our bespoke blog article for more information on importers.

Distributors

Distributors are responsible for ensuring that devices are distributed within the EU in a compliant and safe manner. Their specific duties include:

  • Verification
    Distributors must verify that devices bear CE marking, have a valid Declaration of Conformity, and are appropriately labeled.
  • Record-Keeping
    They are required to keep records of device suppliers and customers to assist in traceability.
  • Reporting
    Distributors must notify manufacturers and authorities if they become aware of any incidents or non-compliant devices.
  • Post-Market Surveillance & Vigilance
    Distributors must support post-market surveillance activities by informing manufacturers of any complaints or incidents related to the devices they handle.

For more information on distributors, read our bespoke blog article.

What is the Unique Device Identification (UDI) system under the IVDR?

One of the key innovations introduced by the IVDR is the Unique Device Identification (UDI) system. UDI systems have existed in other jurisdictions, like the USA, for a long time. The UDI system under the IVDR is designed to significantly enhance the traceability of IVDs throughout their lifecycle, from manufacturing to patient use and post-market surveillance. This change is a direct response to the increasing complexity of supply chains and the need for more robust monitoring of device performance, particularly in terms of safety and efficacy.

Now, the IVDR also introduces the concept of Basic UDI-DI (BUDI), which is an overarching code that identifies a family of IVDs for regulatory traceability purposes. The BUDI must appear on the EU Declaration of Conformity, the technical documentation, and in the EU certificates issued by Notified Bodies.

What can manufacturers do to ensure a compliant transition from IVDD to IVDR?

To ensure a smooth and successful transition to IVDR compliance, manufacturers must adopt a strategic approach by evaluating and updating their processes, technical documentation, and systems. This involves: 

  • Conduct a Gap Analysis
    Evaluate current processes and devices are aligned with the new IVDR requirements. Compare existing quality management processes to those in IVDR Article 10(8). The IVDR requires manufacturers to implement a quality management system (QMS) that aligns with the principles of ISO 13485. Identify gaps in the technical documentation, particularly in clinical evidence, considering the requirements in IVDR Annex II and the applicable General Safety and Performance Requirements (GSPR) in Annex I.
  • Engage with Notified Bodies Early
    Given the high demand for Notified Body services, it’s essential to engage with them early to avoid delays in the certification process.
  • Update Technical Documentation
    Ensure the  technical documentation complies with IVDR standards, including clinical evidence, risk management, and performance evaluation.
  • Implement Post-Market Surveillance Systems
    Set up robust post-market surveillance and vigilance systems to monitor device performance and report any issues promptly.
  • Prepare for UDI Implementation
    Work on implementing the UDI system for your devices to ensure compliance with IVDR traceability requirements.

Here is a guideline to help develop a structured plan for ensuring compliance with IVDR requirements. The table below outlines key aspects and actions to support a seamless transition process:

 

What to Do

Classification

Assess the classification of each device according to IVDR rules. Determine the risk class which is driven by the interned purpose. Adjust technical documentation to meet requirements for the assigned class.

Notified Body Involvement

Engage a Notified Body early. Prepare for conformity assessment by ensuring comprehensive documentation is ready for submission.

General Safety and Performance Requirements (GSPR)

Map GSPRs to the device. Provide detailed documentation showing how each GSPR is met, including clinical evidence and test reports.

Quality Management System (QMS)

Update the QMS to align with IVDR requirements. Document processes for risk management, PMS, and vigilance, ensuring these are integrated into the technical file. Include roles and responsibilities such as PCCR.

Risk Management System

Develop and maintain a risk management system aligned with ISO 14971. Regularly update the risk management file, documenting risk identification, assessment, mitigation, and benefit-risk assessments.

Clinical Evidence and Performance Evaluation

Conduct a performance evaluation. Compile a PER that includes scientific validity, analytical performance, and clinical performance data. Ensure evidence supports all claims.

Post-Market Surveillance (PMS) and PSUR

Develop a PMS plan. Set up a system for collecting and analyzing post-market data. Regularly update and submit Periodic Safety Update Reports (PSUR) as required.

Technical Documentation Structure

Organize technical documentation per IVDR Annexes II and III. Include all required sections, ensuring clarity and completeness.

Labeling and Instructions for Use (IFU)

Revise labeling and IFUs to comply with IVDR. Include clear, user-friendly information. Ensure all updates are reflected in the technical file.

UDI and Traceability

Implement a UDI system. Assign UDIs to devices and maintain accurate documentation of UDI data for traceability.

Economic Operators and Supply Chain Control

Define roles and responsibilities for economic operators. Document all supply chain interactions. Establish processes for monitoring and auditing compliance across the supply chain.

How long do manufacturers have to transition?

The below transitional timelines to upgrade CE-marking from the former IVDD to the EU IVDR, as applicable, have been granted to legacy IVDs:

Diagram showing the transition periods according to the IVDR for legacy IVDs.

Additionally, the document MDCG 2022-8 provides guidance to manufacturers through the extended transition period, ensuring that devices placed on the market under the IVDD prior to May 26th, 2022, can continue to be sold under certain conditions and within the timelines mentioned.

For complete details on legacy devices and transitional requirements, read our bespoke article, here.

How Decomplix can help

The regulatory hurdles have increased significantly with the introduction of the IVDR, and in our experience many manufacturers are struggling with the transition from the IVDD to the IVDR. If you have any specific questions you would like to discuss, please do not hesitate to contact us. We can support your company in fulfilling all the requirements under the EU MDR or IVDR and ensure compliance in the most efficient manner.

If you wish to discuss your needs with us, please contact us for a non-binding quote.

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