MDR vs. IVDR: Understanding the Divergent Paths to CE Marking

The European Union's overhaul of medical device legislation resulted in two parallel regulations: the Medical Device Regulation (EU) 2017/745 (MDR) and the In Vitro Diagnostic Medical Device Regulation (EU) 2017/746 (IVDR). Both regulations entered into force in May 2017, but their application dates and transition timelines have differed significantly.

For manufacturers developing products that may fall under either regulation, or for organizations managing portfolios that span both categories, understanding the fundamental differences between these frameworks is essential for regulatory strategy and resource planning.

Scope and Product Classification

The most fundamental difference between the MDR and IVDR lies in their scope and how products are classified within each framework.

MDR Scope and Classification

The MDR covers medical devices intended for diagnosis, prevention, monitoring, prediction, prognosis, treatment, or alleviation of disease, or for investigation, replacement, or modification of anatomy or physiological processes. The regulation employs a risk-based classification system with four classes:

• Class I: Lowest risk devices, including non-sterile, non-measuring devices without software functions.
• Class IIa: Low to medium risk devices requiring Notified Body assessment of production quality.
• Class IIb: Medium to high risk devices requiring more extensive Notified Body review.
• Class III: Highest risk devices, typically implantables or life-supporting devices, requiring the most stringent conformity assessment.

Classification is determined by applying 22 classification rules set out in Annex VIII of the MDR, which consider factors such as duration of contact, degree of invasiveness, active versus non-active status, and intended use.

IVDR Scope and Classification

The IVDR covers devices intended for in vitro examination of specimens derived from the human body, including blood and tissue donations. The IVDR introduced a fundamentally new classification system with four classes:

• Class A: Lowest risk IVDs, including general laboratory equipment and specimen receptacles.
• Class B: Low to medium risk devices, including devices for self-testing and devices for measuring non-critical parameters.
• Class C: Higher risk devices, including those used for companion diagnostics and blood typing.
• Class D: Highest risk devices, including those used for detecting life-threatening infectious diseases and blood screening.

The IVDR classification rules, found in Annex VIII of that regulation, represent a dramatic shift from the previous list-based system under the IVD Directive. This change has resulted in significant "up-classification" of many IVD products.

Clinical Evidence Requirements

Both regulations place increased emphasis on clinical evidence, but the nature of that evidence differs substantially between device types.

MDR Clinical Evidence

Under the MDR, clinical evaluation is mandatory for all device classes. The clinical evaluation must demonstrate conformity with General Safety and Performance Requirements (GSPRs) and must be based on clinical data. Article 61 and Annex XIV outline the requirements:

• Clinical evaluation process: A systematic and planned process to generate, collect, analyze, and assess clinical data.
• Clinical data sources: Clinical investigations, scientific literature, and clinical experience from equivalent devices.
• Equivalence requirements: Strict criteria for claiming equivalence, including clinical, technical, and biological similarity.
• Clinical investigations: Required for Class III devices and implantables unless justified exceptions apply.

The MDR also introduced Post-Market Clinical Follow-up (PMCF) as a mandatory ongoing activity, with specific PMCF plans and evaluation reports required in technical documentation.

IVDR Performance Evidence

The IVDR uses different terminology, focusing on "performance evaluation" rather than "clinical evaluation." Article 56 and Annex XIII outline these requirements:

• Performance evaluation: Assessment and analysis of data to establish the scientific validity, analytical performance, and clinical performance of a device.
• Scientific validity: The association of an analyte with a clinical condition or physiological state.
• Analytical performance: The ability to correctly detect or measure a particular analyte.
• Clinical performance: The ability to yield results correlated with a particular clinical condition or physiological state.

Performance studies, which may include clinical performance studies involving human subjects, must be planned and conducted in accordance with Annex XIII requirements.

Conformity Assessment Procedures

The conformity assessment routes differ between the two regulations, reflecting their different classification systems and risk profiles.

MDR Conformity Assessment

The MDR provides several conformity assessment procedures in Annexes IX through XI:

• Class I devices: Self-declaration of conformity (with some exceptions for sterile, measuring, or reusable surgical instruments).
• Class IIa devices: Notified Body assessment of quality management system or product verification.
• Class IIb devices: More extensive Notified Body involvement, including technical documentation assessment.
• Class III devices: Full quality management system assessment plus technical documentation review for each device type, with design dossier examination.

IVDR Conformity Assessment

The IVDR conformity assessment routes, also detailed in Annexes IX through XI, differ particularly for higher-risk products:

• Class A devices: Self-declaration of conformity, similar to Class I medical devices.
• Class B devices: Quality management system assessment by Notified Body.
• Class C devices: Technical documentation assessment in addition to QMS review.
• Class D devices: The most stringent requirements, including EU Reference Laboratories verification of device performance.

A notable IVDR-specific requirement is the involvement of EU Reference Laboratories (EURLs) in the conformity assessment of certain Class D devices. EURLs verify the manufacturer's performance data and may conduct laboratory testing.

Post-Market Requirements

Both regulations significantly strengthen post-market surveillance requirements, though with some differences in approach.

Common Requirements

• Post-Market Surveillance (PMS) system: Both regulations require manufacturers to establish and maintain a PMS system proportionate to the risk class.
• Vigilance reporting: Similar timelines and requirements for reporting serious incidents and field safety corrective actions.
• Periodic Safety Update Reports (PSURs): Required for higher-risk devices under both regulations.
• PMS plans and reports: Required documentation demonstrating proactive safety monitoring.

Key Differences

The MDR requires Post-Market Clinical Follow-up (PMCF) activities for all devices except those where clinical evaluation can be fully based on equivalent devices. The IVDR equivalent is Post-Market Performance Follow-up (PMPF), which focuses on ongoing confirmation of performance characteristics.

PSUR requirements also differ slightly: under the MDR, PSURs are required for Class IIa, IIb, and III devices, while under the IVDR, they are required for Class B, C, and D devices. The intervals and content requirements are similar but not identical.

Transition Timelines

The transition timelines have proven to be one of the most challenging aspects of both regulations, with multiple amendments extending deadlines due to implementation challenges.

MDR Timeline

The MDR originally applied from 26 May 2020, but this was delayed by one year to 26 May 2021 due to the COVID-19 pandemic. Subsequent amendments have extended transition periods for devices with valid MDD certificates, with staggered deadlines based on risk class extending through 2027-2028.

IVDR Timeline

The IVDR applied from 26 May 2022. Due to the dramatic impact of reclassification and limited Notified Body capacity, extended transition periods were introduced through Regulation (EU) 2022/112, with deadlines extending from 2025 to 2027 depending on device class.

Strategic Considerations for Manufacturers

For manufacturers operating under both regulations or determining which regulation applies to their products, several strategic considerations are important:

Borderline Products

Some products may fall on the borderline between the MDR and IVDR, or may not clearly fall under either regulation. Examples include products that perform both diagnostic and therapeutic functions, or software that processes IVD results to guide treatment decisions. Early determination of regulatory pathway is essential.

Resource Planning

Organizations managing portfolios under both regulations must plan resources carefully. While some competencies transfer between the two frameworks (quality management, general regulatory knowledge), the specific technical requirements for clinical/performance evaluation, conformity assessment, and technical documentation differ substantially.

Notified Body Strategy

Not all Notified Bodies are designated under both regulations, and those that are may have different scopes for MDR and IVDR. Manufacturers should verify their Notified Body's designation and capacity under the applicable regulation.

Looking Forward

Both the MDR and IVDR continue to evolve through implementing acts, guidance documents, and practical experience. Manufacturers must stay current with developments in their applicable regulation while being aware of how changes in one regulation may signal future changes in the other.

The European Commission and Competent Authorities continue to work on implementation guidance, common specifications, and solutions to capacity constraints. Active engagement with industry associations and monitoring of regulatory developments remains essential for successful compliance.