How to Include the Most Relevant Guidances in Your MDR Clinical Evaluation Report

Introduction

The Medical Device Regulation (EU MDR) has introduced significant changes to the requirements for clinical evaluation of medical devices. This article will provide a comprehensive guide on incorporating the most relevant guidance from MDCG 2020-6, MDCG 2020-5, MDCG 2020-13, MEDDEV 2.7.1 rev4, and EU MDR Annex XIV into your MDR Clinical Evaluation Report (CER). By adhering to these guidances, manufacturers can ensure their CER is compliant with regulatory requirements and demonstrates the safety and performance of their medical device.

1. Complying with EU MDR Annex XIV: Clinical Evaluation Requirements

Annex XIV of the EU MDR outlines the requirements for the clinical evaluation of medical devices. The key points to consider when incorporating these requirements into your clinical evaluation process include:

1A. Demonstration of safety and performance:

Manufacturers must demonstrate the safety and performance of their medical devices through clinical evaluation, which should be based on clinical data that is methodologically sound, relevant, and sufficient.

1B. Risk-benefit analysis:

The clinical evaluation should include a thorough risk-benefit analysis that considers the device’s intended use, performance, and safety. This analysis should weigh the device’s potential benefits against its possible risks.

1C. Clinical evaluation planning:

Manufacturers must develop a clinical evaluation plan (CEP) that outlines the objectives, methodology, data sources, and criteria for appraisal. The CEP should be a living document that is regularly updated throughout the device lifecycle.

1D. Data sources and appraisal:

Clinical data should be obtained from various sources, such as literature, clinical investigations, and post-market surveillance. The data should be appraised for quality, relevance, and strength to ensure it is adequate

2. Adhering to MEDDEV 2.7.1 rev4 Guidelines

The MEDDEV 2.7.1 rev4 is a guidance document titled “Clinical Evaluation: A Guide for Manufacturers and Notified Bodies.” It aims to help manufacturers and notified bodies understand and comply with the requirements for clinical evaluation under the EU Medical Device Directive (MDD) and Active Implantable Medical Devices Directive (AIMDD). Although this guidance is not specifically tailored for the new EU MDR, it is still relevant and useful for manufacturers working to comply with the MDR.

Key aspects of MEDDEV 2.7.1 rev4 include:

2A. Stages of clinical evaluation:

The guidance outlines a three-stage process for clinical evaluation:

1. Identification of pertinent data: Includes defining the device’s intended use, identifying relevant safety and performance endpoints, and collecting data from various sources (e.g., literature, clinical investigations, and post-market surveillance).
2. Appraisal of the data: Involves critically evaluating the quality, relevance, and strength of the collected data to determine its adequacy for demonstrating safety and performance.
3. Analysis of the clinical data: Manufacturers must analyze the appraised data to establish clinical evidence that supports the safety, performance, and risk-benefit profile of the device.

2B. Clinical evaluation planning:

Manufacturers should develop a clinical evaluation plan (CEP) that outlines the approach to collecting, appraising, and analyzing clinical data. The CEP should include the device description, intended use, state of the art, risk analysis, and a clear strategy for data collection and appraisal.

2C. Appraisal of clinical data:

Manufacturers need to assess the quality and relevance of the clinical data, ensuring that it is methodologically sound, unbiased, and sufficient to support the device’s safety and performance claims.

2D. Generating clinical data:

When existing data is insufficient, manufacturers may need to generate additional clinical data through clinical investigations, post-market clinical follow-up (PMCF), or other appropriate means.

2E. Clinical evaluation report preparation and updates:

Manufacturers must prepare a clinical evaluation report (CER) summarizing the results of their clinical evaluation. The CER should be updated regularly based on new data or changes to the device, its intended use, or the state of the art.

3. Understanding the MDCG 2020-6 Guidance

The MDCG 2020-6 titled “Guidance on sufficient clinical evidence for legacy devices under the MDR,” aims to help manufacturers of medical devices marketed prior to the implementation of the EU Medical Device Regulation (MDR) demonstrate sufficient clinical evidence to meet the new regulatory requirements. The guidance specifically addresses the clinical evaluation of legacy devices, which are devices that have been previously approved under the Medical Device Directive (MDD) or Active Implantable Medical Devices Directive (AIMDD).

Key aspects of the MDCG 2020-6 guidance include:

3A. Demonstrating sufficient clinical evidence:

Manufacturers must demonstrate sufficient clinical evidence to support the safety and performance of their legacy devices. This includes a thorough clinical evaluation, which involves a systematic and planned process of gathering, appraising, and analyzing clinical data to verify the safety and performance of a medical device.

3B. The role of clinical investigations:

While clinical investigations may not always be necessary for legacy devices, they might be required in cases where:

1. Existing clinical data is insufficient to support the device’s safety and performance claims.
2. The device has undergone significant changes that could impact its safety or performance.
3. The device belongs to a high-risk category, such as implantable or Class III devices.

3C. Post-market clinical follow-up (PMCF):

PMCF is a continuous process that manufacturers must undertake to update the clinical evaluation. It involves proactively collecting and evaluating clinical data from the use of a device after it has been placed on the market to confirm its safety and performance throughout its expected lifetime. Manufacturers should establish a PMCF plan and incorporate it into their post-market surveillance system.

3D. Updating the clinical evaluation:

Manufacturers are required to update their clinical evaluations regularly, based on the risk profile of the device, the amount and quality of available clinical data, and any new information regarding the device’s safety or performance. Updates should consider post-market surveillance data, including data from PMCF activities, and any relevant scientific literature.

3E. Requirements for legacy devices:

Legacy devices must comply with the EU MDR, which entails a comprehensive re-evaluation of their clinical data. Manufacturers of legacy devices should:

1. Assess whether the existing clinical evaluation complies with the requirements of the MDR and the updated state of the art.
2. Identify any gaps in the clinical data and address them through additional clinical investigations or other appropriate measures.
3. Update the clinical evaluation, considering new scientific literature, post-market surveillance data, and any changes to the device or its intended use.
4. Prepare and maintain an up-to-date clinical evaluation report (CER) as part of their technical documentation.

In summary, the MDCG 2020-6 guidance provides a framework for manufacturers of legacy devices to demonstrate sufficient clinical evidence under the EU MDR. It emphasizes the importance of a thorough clinical evaluation, the potential need for clinical investigations, the role of PMCF, and the continuous updating of the clinical evaluation to ensure the ongoing safety and performance of medical devices.

4. Incorporating MDCG 2020-5 Guidance on Clinical Evaluation and Equivalence

The MDCG 2020-5 guidance, titled “Guidance on Clinical Evaluation (MDR) / Performance Evaluation (IVDR) of Medical Device Software,” provides direction for manufacturers to demonstrate the equivalence between their medical device and another device (the “equivalent device”) as part of the clinical evaluation process. Establishing equivalence can be essential for utilizing existing clinical data from the equivalent device to support the safety and performance claims of the device under evaluation.

Key aspects of the MDCG 2020-5 guidance include:

4A. Defining equivalence:

Equivalence is established when the device under evaluation and the equivalent device have the same intended purpose, similar technical and biological characteristics, and comparable clinical performance. Demonstrating equivalence allows manufacturers to use clinical data from the equivalent device in their clinical evaluation.

4B. Criteria for demonstrating equivalence:

To demonstrate equivalence, manufacturers must provide evidence that the device under evaluation and the equivalent device share the following three characteristics:

1. Technical characteristics: The devices should have similar specifications, design attributes, and principles of operation.
2. Biological characteristics: The devices should interact with the human body in the same way, utilizing similar materials, manufacturing processes, and intended patient populations.
3. Clinical characteristics: The devices should exhibit similar performance and clinical outcomes, taking into account the intended purpose, clinical conditions of use, and target patient population.

4C. Technical, biological, and clinical characteristics:

The guidance provides detailed information on the types of characteristics that should be considered when assessing equivalence, including:

1. Technical: Design, materials, specifications, principles of operation, energy source, and critical performance requirements.
2. Biological: Biocompatibility, tissue/device interaction, patient population, and the presence of medicinal, human tissue, or animal-origin components.
3. Clinical: Intended purpose, medical indications, intended patient population, user profile, medical claims, and clinical performance.

4D. Documentation requirements:

Manufacturers must provide robust documentation to support their claims of equivalence. This includes a thorough comparison of the device under evaluation and the equivalent device, considering their technical, biological, and clinical characteristics. Manufacturers should also provide evidence that they have access to the data from the equivalent device, which may require agreements with the manufacturers of the equivalent device or other legitimate data access arrangements.

4E. Assessing and mitigating risks:

Manufacturers should consider the potential risks associated with claiming equivalence, such as differences in the device’s materials, manufacturing processes, or clinical performance. These risks should be identified, assessed, and mitigated as part of the clinical evaluation process.

In summary, the MDCG 2020-5 guidance provides a framework for demonstrating equivalence between medical devices as part of the clinical evaluation process under the EU MDR. By following this guidance, manufacturers can ensure they have a clear understanding of the criteria for establishing equivalence, the types of characteristics to consider, and the documentation requirements needed to support their claims. Additionally, manufacturers should be aware of the potential risks associated with claiming equivalence and address them accordingly to ensure the safety and performance of their medical device.

5. Including insights from the MDCG 2020-13 Clinical Evaluation Assessment Report Template

The MDCG 2020-13 document provides a template for the Clinical Evaluation Assessment (CEA) report, which is intended to guide notified bodies in their assessment of clinical evaluations conducted by medical device manufacturers under the EU Medical Device Regulation (MDR). The CEA report template is designed to ensure a consistent and harmonized approach when notified bodies review clinical evaluation documentation submitted by manufacturers.

Key aspects of the MDCG 2020-13 CEA report template include:

5A. General Information:

The template begins with a section for general information about the device under evaluation, the manufacturer, the notified body, the assessment team, and the dates of the assessment.

5B. Device Description and Intended Purpose:

This section of the template requires a comprehensive description of the device, including its technical specifications, intended purpose, medical indications, contraindications, target patient population, and any relevant accessories or companion devices.

5C. State of the Art:

In this section, the notified body should assess whether the manufacturer has provided an adequate description of the state of the art in the clinical evaluation report (CER). This includes a review of the relevant scientific literature, existing devices, and current clinical practices.

5D. Essential Requirements:

The notified body should evaluate whether the manufacturer has demonstrated that the device meets the essential safety and performance requirements as specified in the EU MDR.

5E. Clinical Evaluation Plan and Methodology:

This section involves the assessment of the manufacturer’s clinical evaluation plan (CEP) and the methodology used to collect, appraise, and analyze the clinical data. The notified body should determine whether the CEP is appropriate and whether the chosen methodology is scientifically sound and unbiased.

5F. Data Sources and Appraisal:

The notified body should assess the data sources used by the manufacturer in the clinical evaluation, including literature, clinical investigations, and post-market surveillance data. The notified body should also evaluate the manufacturer’s appraisal of the data, ensuring that it is of high quality, relevant, and adequate to support the device’s safety and performance claims.

5G. Analysis of Clinical Data:

In this section, the notified body should assess the manufacturer’s analysis of the clinical data, determining whether the conclusions drawn from the data are valid and supported by evidence. This includes evaluating the risk-benefit profile, clinical performance, and safety of the device.

5H. Conformity Assessment and Post-market Clinical Follow-up (PMCF):

The template requires the notified body to evaluate the manufacturer’s conformity assessment and PMCF activities. This includes determining whether the manufacturer has appropriately considered the need for additional clinical investigations or PMCF activities to support the ongoing safety and performance of the device.

5I. Overall Conclusion:

In the final section, the notified body should provide an overall conclusion on the adequacy of the clinical evaluation, summarizing the main findings and any identified gaps or issues that need to be addressed.

In summary, the MDCG 2020-13 CEA report template is a valuable tool for notified bodies to ensure a consistent approach when assessing clinical evaluations conducted by manufacturers under the EU MDR. By using this template, notified bodies can systematically review and evaluate the different aspects of the clinical evaluation process, including the device description, state of the art, essential requirements, clinical evaluation plan and methodology, data sources and appraisal, analysis of clinical data, conformity assessment, and PMCF activities.

6. MDR Regulatory compliance of your CER

Incorporating the most relevant guidance from MDCG 2020-6, MDCG 2020-5, MDCG 2020-13, MEDDEV 2.7.1 rev4, and EU MDR Annex XIV into your MDR Clinical Evaluation Report is crucial for ensuring regulatory compliance and demonstrating the safety and performance of your medical device. By understanding and adhering to these guidances, manufacturers can confidently navigate the complex EU MDR landscape and bring safe, effective medical devices to market.