Importing investigational devices into Europe under the EU MDR is a complex process that requires strict compliance with regulatory provisions before a clinical investigation can begin. The Medical Device Regulation (MDR) establishes rigorous rules for the entry of investigational devices into the European Union, detailing specific obligations for manufacturers and sponsors. Partnering with a specialized Medical Device Contract Research Organization (CRO) ensures a seamless pathway to compliance and successful device importation.

Essential MDR Provisions for Investigational Device Importation

The MDR delineates vital requirements for the importation of investigational devices:

• Designation of an EU Legal Representative: Non-EU entities must appoint a representative within the EU to ensure adherence to MDR regulations. (See MDR Article 62)
• Conformity with Labeling Standards: Labels on investigational devices must comply with MDR stipulations, encompassing usage instructions, risk information, and device safety and performance details. Compliance with specific language and symbol requirements is essential. (See MDR Annex I Chapter III)
• Demonstration of compliance with the applicable GSPR: This encompasses, when applicable, conducting technical and biological safety assessments, along with pre-clinical evaluations. It also involves implementing measures in occupational safety and accident prevention, all while considering the current state of the art. (See MDR Article 62.4.l)
• Adverse Event Surveillance: Manufacturers and sponsors are obligated to implement a system for tracking and reporting adverse events associated with the investigational device over its entire usage period, adhering to defined adverse event criteria and reporting timelines. (See MDR Article 80)
• Compliance with MDR Article 21: Importation must adhere to MDR Article 21, ensuring the free movement of investigational devices within the EU for clinical investigation.

Role of a Medical Device CRO in Investigational Device Importation

A Medical Device CRO offers comprehensive support:

• Regulatory Guidance: CROs provide deep insights into MDR complexities and keep abreast of regulatory updates.
• Labeling Assistance: They ensure investigational device labeling is in full compliance with MDR.
• Adverse Event Reporting System Establishment: CROs facilitate setting up compliant adverse event reporting systems.
• EU Regulatory Communication: CROs act as liaisons with EU regulatory bodies, managing necessary communications on behalf of manufacturers.
• Documentation and Submission Management: From preparing technical documents to managing submissions and responses to EU authorities, CROs play a pivotal role.

Benefits of Collaborating with a Medical Device CRO

Partnering with a CRO offers numerous advantages:

• Simplified Regulatory Compliance: CROs handle regulatory complexities, freeing manufacturers to concentrate on development.
• Reduced Compliance Risks: Expert advice from CROs minimizes the risks of non-compliance.
• Efficient Market Entry: CROs expedite the process of bringing investigational devices to the EU market.
• Cost Efficiency: By streamlining the importation process, CROs help in curtailing unnecessary costs.
• Expertise Access: CROs offer specialized knowledge in medical device regulation and market entry strategies.

Conclusion

Navigating the MDR for the importation of investigational devices for clinical investigation demands diligent regulatory adherence and strategic planning. Engaging an experienced Medical Device CRO is key to ensuring a compliant and efficient pathway for bringing innovative investigational devices to the EU market.

MDx CRO: Your Strategic Partner for Investigational Device Importation

MDx CRO, a leader in Medical Device CRO services, excels in assisting sponsors and manufacturers through the MDR’s complexities. Our team, proficient in the nuances of the MDR, provides end-to-end support, ensuring your investigational devices are compliantly and effectively introduced into the European market.

With MDx CRO, you gain a partner committed to a compliant, streamlined, and successful introduction of your investigational devices in the EU. Contact us to discover how our expertise can enhance your clinical investigation endeavors.

*MDx offers assistance with the importation of investigational devices. MDx’s range of services does not include acting as an economic operator importer as defined under Article 13 of the EU MDR.

In the intricate world of medical device regulation, the European Union Medical Device Regulation (EU MDR) stands out as a beacon of stringent and comprehensive rules. Among its many provisions, Article 62.2 introduces a pivotal requirement for clinical investigation sponsors outside the European Union. This article delves into the crucial role of a legal representative mandated by this regulation and how it intersects with the ISO 14155 standards for clinical investigations.

Understanding EU MDR Article 62.2

The EU MDR, a cornerstone in medical device regulation, aims to ensure the highest level of safety and performance of medical devices. Under Article 62.2, non-EU sponsors of clinical investigations must appoint a legal representative within the EU. This mandate is more than a procedural formality; it’s a strategic move ensuring that all clinical investigations adhere to the EU’s rigorous standards.

The Legal Representative’s Role and Responsibilities

The legal representative acts as the linchpin, bridging the gap between the sponsor and the EU’s regulatory environment. Their duties are multifaceted and critical:

• Communication Conduit: Acting as the primary contact for EU authorities.
• Regulatory Compliance: Ensuring adherence to EU MDR obligations.
• Documentation Oversight: Maintaining detailed records of clinical investigations.
• Representation: Advocating for the sponsor in discussions with EU authorities.
• Submission and Review Facilitation: Aiding in the efficient handling of necessary documentation.

Throughout the clinical investigation, from inception to conclusion, the legal representative is instrumental in aligning the sponsor’s operations with the EU MDR’s expectations.

Benefits of Engaging a Legal Representative

Appointing a legal representative is not just a regulatory checkbox but a strategic advantage:

• Reduced Regulatory Burdens: They navigate the complexities of the EU MDR, allowing sponsors to focus on their core research activities.
• Enhanced Compliance: With deep insights into the EU MDR, legal representatives ensure effective adherence to the regulations.
• Streamlined Regulatory Interactions: They facilitate smooth communication with EU authorities, removing potential barriers.
• Mitigated Risk of Non-Compliance: Their expertise helps avoid pitfalls that could derail the investigation.
• Accelerated Timelines: Understanding the regulatory landscape enables quicker approval processes.

Selecting the Right Legal Representative

Choosing an effective legal representative hinges on several factors:

• Experience: A history of successful EU clinical investigation management is crucial.
• Expertise: In-depth knowledge of the EU MDR is non-negotiable.
• Communication: They should ensure transparency and regular updates.
• Network: A robust network within the EU regulatory framework can be invaluable.

The Intersection with ISO 14155

The role of a legal representative under the EU MDR complements the ISO 14155 standards, which govern the conduct of clinical investigations for medical devices. Together, they form a robust framework ensuring that clinical investigations meet the highest standards of quality and regulatory compliance.

Conclusion

The appointment of a legal representative under Article 62.2 of the EU MDR is a crucial step for non-EU sponsors aiming to conduct clinical investigations in the EU. This role is not only a regulatory requirement but a vital element in navigating the EU’s regulatory landscape, in line with ISO 14155 standards. With the right legal representative, sponsors can focus on their primary objective – advancing medical science and patient care.

The Medical Device Coordination Group (MDCG) plays a key role in setting the rules for medical devices in the European Union. One of its most important guidelines is MDCG 2020-13, which focuses on how to create Clinical Evaluation Reports (CER) under the EU’s Medical Device Regulation (MDR). Understanding this guideline is essential for complying with EU rules and successfully marketing your products there.

Why MDCG 2020-13 Matters?

The new MDR has significantly altered the compliance landscape, making it more complex but also more standardized. It has heightened the importance of a detailed and well-structured Clinical Evaluation Report as part of your Technical Documentation. The MDCG 2020-13 guidance provides manufacturers with valuable insights on how to prepare a CER that meets the requirements of the Medical Device Regulation (MDR). By following the guidance, manufacturers can increase their chances of successful regulatory approval for their medical devices.

MDCG 2020-13 is aimed at providing guidance on the clinical evaluation process for medical devices. Given the complexity and significance of clinical data in proving the safety and performance of a device, MDCG 2020-13 acts as a crucial resource. It details what should be included in the Clinical Evaluation Report, and it does so in a manner that aligns with the new MDR, thereby ensuring that you meet the most current regulatory requirements.

Aligning Clinical Evaluation (CER) with Clinical Evaluation Assessment Report (CEAR) Structure

Manufacturers should be aware that the Clinical Evaluation Report can also be prepared aligned with the Clinical Evaluation Assessment Report (CEAR) structure. This approach aids in a more streamlined, comprehensive evaluation of your device, making the regulatory journey smoother.

MDCG 2020-13 and Its Impact on Clinical Evaluation Plan

MDCG 2020-13 delves deeply into the specifics of the clinical evaluation plan, highlighting the importance of several key aspects that manufacturers must pay attention to. This guidance reiterates the necessity of aligning the clinical evaluation plan with the Annex XIV Part A Section 1a requirements.

MDCG 2020-13 explicitly instructs manufacturers to ensure the clinical evaluation plan encompasses the following:

• General Safety and Performance Requirements: Identify which requirements necessitate support from clinical data.
• Intended Purpose: Clearly specify the device’s intended purpose, which must be consistent throughout the evaluation process.
• Target Groups: Detail the target groups, their indications, and contra-indications, a crucial aspect of ensuring patient safety.
• Clinical Benefits: Define the clinical benefits and associated outcome parameters, providing concrete metrics for evaluation.
• Qualitative and Quantitative Aspects of Clinical Safety: Specify the methods to be employed in assessing both qualitative and quantitative aspects of clinical safety, focusing on the identification of residual risks and side-effects.
• Benefit-Risk Ratio: Include a comprehensive list of parameters to assess the benefit-risk ratio in line with the current state of medical science.
• Special Components: Indicate how you will address benefit-risk issues tied to specialized components like pharmaceutical substances, animal tissues, or human tissues.
• Clinical Development Plan: While a detailed description may not always be required, MDCG 2020-13 insists on the inclusion of a clinical development plan, complete with milestones and acceptance criteria.

MDCG 2020-13 also mandates that the clinical evaluation plan must:

• Adequately Address Safety: Assess both qualitative and quantitative aspects of clinical safety, detailing methods for determining residual risks and side-effects.
• Document Clinical Data for Performance: Summarize the clinical data that proves the device’s performance in achieving its intended purpose and thereby contributing to clinical benefits for patients.
• Review Past Issues: If relevant, the plan should summarize any significant complaints or vigilance issues associated with earlier device iterations and evaluate their impact on the current clinical evaluation assessment.

Aligning IFU and Promotional Materials with the CER Following MDCG 2020-13

The synergy between Instructions for Use (IFU), promotional materials, and the Clinical Evaluation Report (CER) is crucial for regulatory compliance and, more importantly, for ensuring patient safety and device efficacy. Following MDCG 2020-13 guidelines can be a strategic move to align these critical documents. Below we explore this alignment:

• Information Materials Supplied by the Manufacturer: In accordance with MDCG 2020-13, it is essential to conduct a review of all documents supplied by the manufacturer. This includes IFUs, promotional materials, Summary of Safety and Clinical Performance (SSCP), labeling, and more.
• Intended Purpose: Verify that the clinical evidence cited in the CER supports the intended purpose of the device as described in the IFU and promotional materials.
• Intended Patient Population: Ensure that the patient population identified in the CER aligns with that in the IFU and promotional materials.
• Safety Measures: Assess whether all appropriate warnings or contraindications are included for the intended patient population.
• Intended Users: Identify whether the device is designed for healthcare professionals or lay users. Check if the IFU includes information for the intended user, taking into account their technical knowledge, experience, and educational background.
• User Training: Determine if training is required for the intended users and verify that this is justified in both the risk management file and the CER.
• Limitations and Contraindications: The manufacturer must clearly describe any limitations and contraindications for the device. The CER should support these statements.
• Warnings and Precautions: Verify that warnings, precautions, and measures for malfunctions are adequately described.
• Associated Risks: Evaluate if the estimation of associated risks and residual risk is either quantitative or qualitative and whether this description is appropriate for both patients and users.

By aligning these documents in accordance with MDCG 2020-13, manufacturers not only assure compliance but also build a strong foundation for market success, bolstered by robust clinical evidence and transparent communication.

How to Incorporate these Aspects in Your Clinical Evaluation

1. Perform a Gap Analysis

• Action: Perform a gap analysis to compare your existing clinical evaluation against the new requirements outlined in MDCG 2020-13.
• Outcome: This will help you identify areas that need attention and allow you to make data-driven decisions for improvement.

2. Engage Multidisciplinary Teams

• Action: Assemble a team  of regulatory experts, clinical professionals, and statisticians to holistically address the facets of the new guidelines.
• Outcome: Leveraging diverse expertise ensures a thorough and compliant clinical evaluation process.

3. Update Documents

• Action: Revise your clinical evaluation documentation to ensure it encompasses all the points highlighted in the gap analysis.
• Outcome: With all the critical elements in place, you will be well-prepared for any regulatory scrutiny and audits.

4. Consistent Device Description

• Action: Ensure the device description used for the clinical evaluation aligns with other documents such as the IFU and promotional materials.
• Outcome: This will ensure clarity and cohesion across all documentations, making regulatory compliance easier to demonstrate.

5. Integrate Available Clinical Data

• Action: Incorporate data from clinical investigations, Post-Market Clinical Follow-up (PMCF) studies, and other relevant sources into your updated clinical evaluation.
• Outcome: This enhances the credibility of your CER and provides a richer context for assessing the device’s safety and performance.

6. Utilize PMS Reports or PSUR

• Action: Review Post-Market Surveillance (PMS) reports or Periodic Safety Update Reports (PSUR) and incorporate updates as necessary into the IFU and other promotional materials.
• Outcome: By doing this, you align your clinical evaluation with real-world data, thereby improving the reliability of your overall evaluation.

7. Consistency with Risk Management File

• Action: Verify that all risk-related information across different documents, including the IFU and promotional materials, is consistent with the risk management file.
• Outcome: Such alignment strengthens your compliance while also enhancing patient safety by ensuring that risk assessments are uniform across all materials.

By following MDCG 2020-13 to the letter, you don’t just comply with the regulations—you elevate the robustness and credibility of your clinical evaluation, thereby mitigating risks and accelerating your time-to-market.

Final Thoughts

MDCG 2020-13 is more than just another regulatory guideline; it’s a foundational element for any manufacturer looking to market their medical devices in the EU.

Aligning your Clinical Evaluation Report with the CEAR structure can provide an additional layer of robustness to your documentation, potentially accelerating your time to market. Understanding and implementing the recommendations from MDCG 2020-13 is not just about compliance; it is about ensuring the safety and performance of medical devices that have a profound impact on human health.

For any further assistance on navigating the complexities of MDCG 2020-13, feel free to reach out to us. We specialize in supporting medical device manufacturers in their journey towards MDR compliance.

In this article, we will delve into the intricacies of developing a robust Clinical Evaluation Plan using expert regulatory terminology, equipping you with the knowledge to navigate this essential aspect of your MedTech product development.

As the medical device industry evolves and regulatory requirements become more stringent, the need for a well-defined Clinical Evaluation Plan (CEP) has become paramount.

The CEP plays a crucial role in assessing the safety and performance of medical devices, ensuring their compliance with Annex XIV of the Regulation (EU) MDR 2017/745 (MDR), MDCG 2020-6, and MEDDEV 2.7.1. Rev.4.

In this article, we will delve into the intricacies of developing a robust Clinical Evaluation Plan using expert regulatory terminology, equipping you with the knowledge to navigate this essential aspect of your MedTech product development.

1. Clinical evaluation of your medical device

The clinical evaluation shall be thorough and objective, and both favourable and unfavourable data should be considered for the Clinical Evaluation Plan.

Its depth and extent shall be proportionate and appropriate to the nature, classification, intended purpose, manufacturer’s claims in respect of the device and risks of the device in question.

A clinical evaluation may be based on clinical data relating to a device for which equivalence to the device in question can be demonstrated.

Demonstration of equivalence should be based on demonstration of technical, biological, and clinical equivalence between the device under evaluation and the selected equivalent device. Notified Bodies highly recommend claiming equivalence against only one equivalent device.

According to MDR Article 61(1) and Annex XIV, manufacturers shall plan, conduct and document a clinical evaluation. The planning of the clinical evaluation shall be documented in a Clinical Evaluation Plan.

Moreover, the results of the clinical evaluation and the clinical evidence on which it is based shall be documented in a Clinical Evaluation Report.

2. What is a Clinical Evaluation Plan?

The Clinical Evaluation Plan, also known as CEP, is a documented strategy that outlines the systematic and planned approach for assessing the safety and performance of a medical device throughout its lifecycle. 

It provides a comprehensive framework for conducting the clinical evaluation, which includes gathering and analyzing clinical data to establish the device’s conformity with the General Safety and Performance Requirements (GSPRs) outlined in Annex I of the MDR.

3. Navigating Annex XIV of MDR 2017/745: What To Consider?

According to the first section of Part A of Annex XIV of MDR, the CEP should be established and timely updated by the manufacturer to ensure that the clinical evaluation is planned , continuously conducted, and documented.

The minimum requirements of the CEP outlined in Annex XIV of MDR are:

• An identification of the GSPRs that require support from relevant clinical data.
• A specification of the intended purpose of the device.
• A clear specification of intended target groups with clear indications and contraindications.
• A detailed description of intended clinical benefits to patients with relevant and specified clinical outcome parameters.
• A specification of methods to be used for examination of qualitative and quantitative aspects of clinical safety with clear reference to the determination of residual risks and side-effects.
• An indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the indications and intended purpose of the device.
• An indication how benefit-risk issues relating to specific components such as use of pharmaceutical, non- viable animal or human tissues, are to be addressed.
• A clinical development plan indicating progression from exploratory investigations, such as first-in-man studies, feasibility, and pilot studies, to confirmatory investigations, such as pivotal clinical investigations, and a PMCF with an indication of milestones and a description of potential acceptance criteria.

Moreover, manufacturers should also consider the following points for their Clinical Evaluation Plan:

3.1. Clinical data from systematic scientific literature review

A systematic scientific literature review should be conducted to identify available clinical data that are relevant to the device and its intended purpose.

This review should also highlight any gaps in the existing clinical evidence, ensuring a comprehensive understanding of the current knowledge landscape.

Conducting the systematic literature review based on PRISMA and PICO methodologies is recommended due to the fact these literature search methods contribute to ensure the systematicity and reproducibility of the search.

3.2. Clinical data from clinical investigations

Properly designed clinical investigations as per the Clinical Development Plan should be designed and conducted for your Clinical Evaluation Plan.

These investigations should aim to generate any new or additional clinical data necessary to address outstanding issues and further establish the safety and performance of the device.

3.3. Clinical data appraisal and suitability

All relevant clinical data should be appraised by evaluating their suitability for establishing the safety and performance of the device.

This evaluation should consider the quality, reliability, and relevance of the data, as well as the suggested hierarchy of clinical evidence for confirmation of conformity with relevant GSPRs under the MDR of Appendix III of MDCG 2020-6.

3.4. Clinical data analysis and conclusions

All relevant clinical data should be analyzed, including data from literature reviews, existing clinical studies, and newly generated data from clinical investigations.

The analysis should aim to draw meaningful conclusions about the safety and clinical performance of the device, including its clinical benefits.

This process involves rigorous data interpretation, statistical analysis, and consideration of risk-benefit assessments to support robust and evidence-based conclusions for your Clinical Evaluation Plan.

4. Navigating MDCG 2020-6: What To Consider?

The MDCG 2020-6 “Regulation (EU) 2017/745: Clinical evidence needed for medical devices previously CE marked under Directives 93/42/EEC or 90/385/EEC – A guide for manufacturers and notified bodies – April 2020” provides detailed guidance on the clinical evaluation of medical devices in accordance with the requirements of the MDR.

4.1. Documentation

MDCG 2020-6 points out that manufacturers are required to document a Clinical Evaluation Plan to meet the requirements of MDR Annex XIV, and provides further advice to successfully comply with MDR Annex XIV Section 1a:

• Identification of the relevant GSPRs.
• Specification of the intended purpose, target groups, indications, contraindications.
• Detailed description of intended clinical benefits with relevant and specified clinical outcome parameters.
• Specification of qualitative and quantitative aspects of clinical safety and performance.

4.2. Sources of clinical data

Moreover, the Clinical Evaluation Plan shall include the identified sources of clinical data, either:

• Pre-market clinical data: clinical investigation reports of the device concerned; clinical investigation reports or other studies reported in scientific literature, of a device for which equivalence to the device in question can be demonstrated; reports published in peer reviewed scientific literature on other clinical experience of either the device in question or a device for which equivalence to the device in question can be demonstrated; other pre-market data, such as case reports on experience with the use of the device in question).
• Post-market clinical data: PMS clinical data, complaint and incident reports; PMCF studies, including post-market clinical investigations; independent clinical studies conducted using the device; device registries; or data retrieved from the literature)
• New generated clinical data. 

The system of appraisal and analysis of clinical data shall also be presented in the CEP.

4.3. Minimum content

Furthermore, the minimum content for a Clinical Evaluation Plan for legacy devices is presented in Appendix II of this MDCG:

• An identification of the GSPR that requires support from relevant clinical data.
• A specification of the intended purpose of the device.
• A clear specification of intended target groups with clear indications and contra- indications.
• A detailed description of intended clinical benefits to patients with relevant and specified clinical outcome parameters.
• A strategy to identify, analyze and assess alternative treatments.
• A specification of methods to be used for examination of qualitative and quantitative aspects of clinical safety with clear reference to the determination of residual risks and side-effects.
• An indicative list and specification of parameters to be used to determine, based on the state of the art in medicine, the acceptability of the benefit-risk ratio for the various indications and for the intended purpose or purposes of the device.
• An indication how benefit-risk issues relating to specific components such as use of pharmaceutical, non- viable animal or human tissues, are to be addressed.
• A strategy and methodology to identify, analyze and appraise all relevant available clinical data in light of the changed definition for clinical data.
• Evidence for equivalence if clinical data from an equivalent device is included in the clinical evaluation.
• A definition of the required level of clinical evidence, which shall be appropriate in view of the characteristics of the device and its intended purpose.
• A strategy and methodology to systematically collect, summaries and assess post market surveillance data to demonstrate continuing safety and performance, and to what extent complaints with regards to safety and performance have been observed with the legacy devices.

Furthermore, Appendix III of MDCG 2020-6 provides a hierarchy of clinical evidence for confirmation of conformity with relevant GSPRs under the MDR.

This suggested hierarchy of clinical evidence ranks different types of clinical data and evidence from strongest to weakest and provides considerations to apply for your Clinical Evaluation Plan.

Taking into consideration the suggested hierarchy of clinical evidence as part of the appraisal methodology of your clinical data is recommended.

5. Navigating MEDDEV 2.7.1. Rev.4: What To Consider?

MEDDEV 2.7.1. Rev.4 refers to the fourth revised version of the Medical Device Vigilance Guidance Document.

This document encourages the adoption of a standardized approach to clinical evaluation for medical devices that fall under the regulation of directives 90/385/EEC and 93/42/EEC.

MEDDEV 2.7.1 Rev.4 continues to be used even after the implementation of MDR since it offers additional interpretive guidance and practical recommendations that complement the MDR requirements.

Section 7 of MEDDEV 2.7/1 rev. 4 addresses the definition of scope of the clinical evaluation, which constitutes the Stage 0 of a clinical evaluation, and, according to MDR and MDCG 2020-6, states that the manufacturer should set up a Clinical Evaluation Plan for the device under evaluation. 

Recognizing the wide range of technologies employed in medical devices, along with their diverse histories and associated risks, is crucial.

Therefore, Section 7 of MEDDEV 2.7/1 rev. 4 also examines the different aspects to be considered for setting up a CEP depending on the stage in the lifecycle of the product and its regulatory status (i.e., before CE-marking, For CE-marked devices).

Moreover, Appendix A3 of MEDDEV 2.7/1 rev. 4 lists information that can be relevant for planning clinical evaluations. It is paramount that the manufacturer ensures that input for the Clinical Evaluation Plan shows alignment with the device’s “label, instructions for use, promotional or sales materials or statements” and with the device’s updated risk management documentation.

Considerations for your Clinical Evaluation Plan Template MDR-based

At MDx CRO, we recognize the significance of a well-structured Clinical Evaluation Plan (CEP) in ensuring the safety and performance of medical devices.

The design of a Clinical Evaluation Plan (CEP) template according to the Medical Device Regulation (MDR) 2017/745 should be tailored to the specific typology of the manufacturer’s device.

This customization is critical as every medical device has unique attributes, different indications for use, target populations, and risk profiles.

Therefore, the use of a generic template for all devices is not recommended. Although it might be tempting to use a “one-size-fits-all” approach for efficiency reasons, such practice could overlook the MDR’s specific requirements for each individual device, potentially leading to non-compliance with established safety and efficacy standards.

Additionally, lack of specificity could lead to erroneous or inappropriate conclusions in the clinical evaluation, jeopardizing the device’s approval for marketing. In summary, it is essential that each Clinical Evaluation Plan is designed and tailored specifically for the device being evaluated, in line with the guidelines of the MDR 2017/745.

Despite the unique considerations required for each device’s Clinical Evaluation Plan (CEP) under the MDR 2017/745, we understand the value of having a general framework to start from. Therefore, we will provide a template that serves as a starting point for the development of a Clinical Evaluation Plan.

This template will include essential elements required under the MDR 2017/745 such as:

• Plan rationale
• Device description
• Clinical background
• Identification of pertinent data sources
• Clinical evaluation method
• Plan for the appraisal of clinical data.

Remember, this is a guide to help initiate the process and not a final document. You will need to tailor the template to fit your specific device, its indications, target population, risk factors, and other device-specific attributes.

Our intention is to help streamline the process, providing structure while also emphasizing the importance of customization to meet the regulatory requirements.

Clinical Evaluation Plan Template Guidance

To streamline the development process and enhance compliance with regulatory standards, a guidance template of the contents of the CEP is provided below:

• SECTION 1. SUMMARY; SECTION 2. REFERENCES; SECTION 3. ACRONYMS AND DEFINITIONS; SECTION 4. RESPONSIBILITIES; SECTION 5. SCOPE OF THE CLINICAL PLAN AS PART OF THE CLINICAL EVALUATION

This section should address GSPR, previous clinical evaluations, CEP and potential deviations to the CEP, IFU and labeling of the device, and risk management.

• SECTION 6. DEVICE DESCRIPTION

This section should include device name, device classification, brief device description, device components and materials, and device size and models. In addition, the manufacturer name, the device’s generic device group, and the device lifecycle should be indicated.

Moreover, the intended purpose and how the device achieves its intended purpose, the clinical condition, the target patient population and target user group, as well as the contraindications, warnings, cautions, precautions and undesirable effects of the device in question should also be detailed.

• SECTION 7. CLINICAL BACKGROUND,AND STATE OF ART

This section should present the sources to be used, the applicable standards and guidance documents, as well as the State Of The Art, including benchmark device and other available treatment options.

• SECTION 8. EVALUATION OF THE DEVICE

This section should address the type of evaluation to be conducted, the safety and performance parameters, the demonstration of device equivalence (if applicable), the sources of clinical data identified, such as data generated and held by the manufacturer data from scientific literature search (i.e., systematic literature review), and data from post-market surveillance and vigilance reporting.

• SECTION 9. ANALYSIS OF CLINICAL DATA

This section should present the methods for evaluation of: safety (GSPR 1 to 8), performance (GSPR 1), benefit-risk profile and acceptability of undesirable side effects (GSPR 8), and other additional clinical claims.

• SECTION 10. CLINICAL DEVELOPMENT PLAN; SECTION 11. ADDITIONAL ITEMS FROM APPENDIX II OF MDCG 2020-6 (LEGACY DEVICE)

This section should include pre-market and/or PMCF clinical Investigations, if applicable

• SECTION 12. PMS AND PMCF PLANS; SECTION 13. FREQUENCY OF CLINICAL EVALUATION UPDATES; SECTION 14. DATES AND SIGNATURES; SECTION 15. ANNEXES

This template serves as a valuable resource, guiding you through the essential components of a Clinical Evaluation Plan, from device description and clinical data requirements to risk-benefit analysis and post-market clinical follow-up plans.

How are medical devices without an intended medical purpose regulated under the MDR Annex XVI? Continue reading to learn more.

The Medical Devices Regulation (MDR) 2017/745 has significantly changed the European Union’s (EU) regulatory landscape for medical devices.

While prioritizing patient safety and efficacy, this regulation introduces a fascinating aspect: including medical devices without an intended medical purpose. Let’s explore the key highlights of the MDR Annex XVI and delve into the world of these intriguing devices.

What is new?

The MDR 2017/745 replaces the previous Medical Devices Directive (MDD) and enforces stricter requirements for manufacturers, notified bodies, and competent authorities.

One notable change is the expanded scope of medical devices to include products without an intended medical purpose, a departure from traditional definitions – a scope reflected under the MDR Annex XVI.

Medical Devices without an Intended Medical Purpose:

Under the MDR Annex XVI, certain products are categorized as medical devices even if they lack an intended medical purpose. Examples include:

• Contact lenses without correction of vision (ex: colored contact lenses)
• Devices to modify the anatomy or fixation of body parts (ex: subdermal implants such as breast implants)
• Facial and dermal fillers for skin enhancements (ex: dermal fillers)
• Equipment for body shaping and fat reduction (ex: liposuction equipment)
• High-intensity radiation devices for skin treatment, such as IPL (Intense pulsed light), lasers and infrared equipment (ex: tattoo or hair removal lasers, equipment for hair removal or skin rejuvenation).
• Non-invasive brain stimulation devices (ex: devices for transcutaneous electrical nerve stimulation (TENS) for aesthetic purposes)

And how are these medical devices from MDR Annex XVI commonly classified?

Discover the classification of these devices according to the rules outlined in MDR 2017/745 Annex VIII. However, it’s important to note that not all rules can be applied. For instance, rules 9 and 10, which pertain to active therapeutic and diagnostic devices, assume a medical purpose.

To address this, a Commission Implementing Regulation (2022/2347) was introduced to reclassify relevant devices alongside the Common Specifications. Let’s take a closer look at the classification of specific product classes:

1. Body shaping devices are categorized as Class IIb, as detailed in Section 4.
2. Devices for skin rejuvenation, hair removal, and similar purposes may fall under Class IIa or IIb, depending on the application. This classification is explained in Section 5.
3. Equipment for transcranial brain stimulation is classified as Class III and is covered in Section 6.

Annex XVI Medical devices: key regulations

Here are the key regulations of medical devices without an intended medical purpose according to the MDR 2017/745:

• Safety and Performance: Ensure devices are designed and manufactured for safe and effective use, with a risk analysis and mitigation measures in place.
• Conformity Assessment: Carry out a conformity assessment procedure to demonstrate compliance with relevant requirements, potentially involving a notified body.
• Technical Documentation: Prepare and maintain documentation showcasing device conformity, including design, intended purpose, manufacturing processes, and risk management.
• Post-Market Surveillance: Establish a system to monitor and analyze device performance and safety, promptly investigate complaints or adverse events, and take corrective actions.
• Unique Device Identification (UDI): Assign a unique device identifier (UDI) to enable traceability and provide corresponding information in a UDI database.
• Clinical Evaluation and Investigation: Conduct a clinical evaluation based on available data to assess device safety and performance, with clinical investigations if needed.
• Labeling and Instructions: Properly label devices and provide clear instructions for use, including intended purpose, handling, storage, and relevant warnings or contraindications.

The MDR 2017/745 revolutionizes the medical device industry by emphasizing safety, performance, and post-market surveillance.

Notably, the regulation expands its scope to include medical devices without a medical purpose. By encompassing these devices, the MDR addresses the evolving landscape of healthcare technologies and their impact on human health.

By partnering with MDx CRO, manufacturers can ensure compliance with the MDR and successfully bring their Medical Devices without an Intended Medical Purpose to the European market.

MDx CRO offers expertise in navigating the complex regulatory landscape, providing guidance and support throughout the compliance process. Together, we can ensure that these innovative devices meet the necessary safety and performance standards, opening doors to new opportunities in the European healthcare market.

FAQs

How does MDR define “intended medical purpose” for medical devices?

The MDR 2017/745 focuses on the term “intended purpose”, which means the use for which a device is intended according to the data supplied by the manufacturer on the labeling, in the instructions for use, or in promotional materials.

While the MDR does not provide an explicit definition for “intended medical purpose,” it is generally understood as the purpose for which a medical device is intended to be utilized within the medical field. The intended purpose of a medical device refers to the specific medical functions it is intended to perform, such as diagnosis, treatment, monitoring, prevention, or alleviation of disease or injury.

Are there any exemptions or special considerations for medical devices without an intended medical purpose?

Yes, the MDR 2017/745 provides some special considerations for medical devices without an intended medical purpose. The main considerations are:

Manufacturers of products without an intended medical purpose shall comply with the relevant common specifications for those products, based on Article 9(4) of MDR. The common specifications related to these products shall address, at least, the application of risk management as set out in Annex I of MDR and, where necessary, clinical evaluation regarding safety.

Regarding the clinical evaluation, the requirement to demonstrate a clinical benefit in accordance with Chapter VI and Annexes XIV and XV of MDR 2017/745 shall be understood as a requirement to demonstrate the performance of the products without an intended medical purpose, according to article 61(9). Clinical evaluations of those products shall be based on relevant data regarding safety, including data from post-market surveillance, post-market clinical follow-up, and, if applicable, specific clinical investigations. Clinical investigations shall be conducted for these products unless reliance on existing clinical data from an analogous medical device is duly justified.

Considering Annex I of MDR 2017/745, Chapter I(9), the general safety requirements established in Sections 1 and 8 shall be understood to mean that these devices, when used under the conditions and for the purposes intended, do not present a risk at all or present a risk that is no more than the maximum acceptable risk related to the product’s use which is consistent with a high level of protection for the safety and health of persons.

Are there any specific labeling or instructions for use (IFU) requirements for medical devices without an intended medical purpose under MDR 2017/745?

Yes, devices without an intended medical purpose have specific requirements for IFU, but not for labeling. According to Annex I of MDR 2017/745, point 23.4 (x), information regarding the absence of a clinical benefit and the risks related to the use of the device should be included in the IFU.