The Medical Device Regulation (MDR) 2017/745 has transformed the EU’s regulatory landscape for medical devices. It aims to boost patient safety and transparency. The regulation sets strict criteria for clinical investigations. In this context, MDCG 2021-6 Rev. 1 is key. Issued by the Medical Device Coordination Group (MDCG), it underwent a revision in December 2023.
This update offers valuable insights. It addresses common questions about clinical investigations under MDR. The impact is wide-reaching. Manufacturers, sponsors, competent authorities, research centers, ethics committees, legal representatives, and CROs are all affected. This guide explores MDCG 2021-6 Rev. 1’s vital aspects. Moreover, it highlights its implications for these stakeholders.
Introduction to MDCG 2021-6 Rev. 1
MDCG 2021-6 Rev.1 is a cornerstone document for those embarking on clinical investigations of devices within the scope of the Medical Device Regulation (EU) 2017/745 (MDR). Designed for sponsors, this evolving guide may expand with more questions and answers over time. It clarifies the use of the term ‘device’ in line with MDR. This includes medical devices, their accessories, and specific products listed in Annex XVI.
The guide also standardizes the definition of “clinical investigation.” It aligns with Article 2(45) of the MDR, focusing on investigations aimed at assessing a device’s safety or performance. Moreover, it introduces the broader concept of “clinical study.” This encompasses a range of research activities within medical science. It includes clinical trials of medicines, device investigations, and in vitro diagnostic studies. These elements are vital for understanding the full scope of clinical research.
This document touches on key topics crucial for navigating the regulatory landscape:
- Proof of Concept Studies: Offering insights into the initial stages of device development.
- Article 82 Clinical Studies: Clarifying the scope of broader research activities under MDR.
- Pilot Stage Investigations: Defining early feasibility and its regulatory implications.
- Regulatory Pathways: Shedding light on navigating clinical investigations amidst the interplay of MDR, the Clinical Trial Regulation (CTR), and local laws.
- Combined Trials: Addressing the complexities of studies involving both medicinal products and medical devices.
- Invasive or Burdensome Considerations: Guiding sponsors on ethical and participant safety considerations.
- Usability Testing: Outlining when such tests are considered clinical investigations.
- Retrospective Testing: Distinguishing between prospective data collection and the analysis of existing data.
- Submissions and Modifications: Offering guidance on navigating regulatory submissions and changes during the clinical investigation process.
- Legal Representation: Emphasizing the role of legal representatives in ensuring compliance.
Some of the Key Highlights of MDCG 2021-6 Rev. 1
MDCG 2021-6 Rev. 1 offers an in-depth exploration into the clinical investigations aspects under the Medical Device Regulation (EU) 2017/745 (MDR). This document is instrumental in bridging the regulatory gaps and ensuring a harmonized approach across the European Union. Here are the refined key highlights based on the updated request:
Regulatory Pathways and Documentation
The document elaborates on navigating the regulatory landscape for conducting clinical investigations. It includes guidance on choosing the correct regulatory pathway, be it for a novel device entering early-stage clinical investigation or for further assessment of a CE-marked device. Detailed documentation requirements facilitate sponsors in preparing comprehensive applications, streamlining the approval process.
Legal Representative’s Role and Responsibilities
The document provides clarity on the responsibilities of the sponsor’s legal representative, which is pivotal for non-EU manufacturers. It underlines the need for a legal representative within the EU to ensure compliance with MDR requirements. This representative acts as a point of contact between the non-EU sponsor and the EU regulatory authorities, facilitating the submission and communication processes.
Substantial Modifications
Understanding what constitutes a substantial modification is crucial for the continuity and compliance of clinical investigations. MDCG 2021-6 Rev. 1 details the criteria for identifying substantial modifications that could impact the safety, health, or rights of subjects, or the reliability and robustness of the clinical data.
This guidance aids sponsors in navigating the process for notifying competent authorities about such modifications, ensuring that the integrity and validity of the investigation are maintained.
Relationship with the CTR, Combined Trials, and Combination Products
The document delves into the interplay between medical device regulations and the Clinical Trials Regulation (CTR), particularly in the context of combined trials and combination products. It highlights the importance of navigating both regulatory frameworks when a study involves medical devices and medicinal products. This includes guidance on conducting clinical studies that collect data for both devices and associated medicinal products, ensuring compliance with the MDR and CTR. The document’s insights into handling combination products—where devices and medicinal substances are integrated—are crucial for sponsors planning such studies.
Clarifications on Specific Aspects of Clinical Investigations
MDCG 2021-6 Rev. 1 sheds light on several nuanced areas of clinical investigations:
- Usability Testing: It clarifies when usability tests are considered clinical investigations.
- Invasiveness Considerations: The document defines what constitutes invasive procedures and the implications for clinical investigations, emphasizing the importance of assessing the invasiveness level when planning studies.
- Retrospective Studies: Insights are provided on the role of retrospective studies within clinical investigations, delineating when such studies fall under the scope of clinical investigation definitions and how they contribute to clinical evaluations.
- Proof of Concept Studies: Guidance on conducting proof of concept studies is highlighted, including their significance in the early stages of device development and their regulatory considerations under the MDR.
In-Depth Highlights of MDCG 2021-6 Rev. 1 for Specialized Clinical Investigations
Proof of Concept Studies according MDCG 2021-6 Rev. 1
Proof of Concept (PoC) studies are instrumental in the nascent phases of medical device development. These studies aim to demonstrate the feasibility and potential clinical benefits of a device, laying the groundwork for subsequent development stages. MDCG 2021-6 Rev. 1 provides comprehensive guidance on PoC studies, emphasizing their critical role in validating device concepts and navigating the regulatory framework of the MDR.
PoC studies serve as a foundational element in device development, enabling sponsors to assess a device’s early clinical viability and address potential design modifications before advancing to more comprehensive clinical trials. The guidance from MDCG 2021-6 Rev. 1 ensures that these studies are conducted within a framework that prioritizes patient safety, scientific validity, and regulatory compliance.
By focusing on detailed planning, ethical conduct, and adherence to specified regulatory pathways, PoC studies under the guidance of MDCG 2021-6 Rev. 1 facilitate a smoother transition through the early stages of device development.
MDCG 2021-6 Rev. 1 delineates the regulatory pathways essential for conducting PoC studies that support the conformity assessment of the device under investigation. It specifies the need for a meticulously detailed Clinical Investigation Plan (CIP), ensuring that PoC studies are grounded in solid scientific rationale and ethical considerations. This guidance is particularly highlighted in:
- Question 7, which discusses the regulatory pathways for clinical investigations aimed at supporting device conformity assessments.
- Question 11, focusing on the investigational use of CE-marked devices for new potential applications or further PoC studies.
- Question 8, which identifies clinical investigations considered at the pilot stage, setting the stage for PoC studies.
- Question 9, providing a roadmap for conducting early feasibility and first-in-human studies under the MDR, underscoring the importance of thorough risk assessment and ethical considerations.
Combined Trials
Combined Trials represent a pivotal area of focus within the regulatory landscape of clinical investigations, particularly when these involve both medical devices and medicinal products.
The MDCG 2021-6 Rev. 1 and MDCG 2022-10 documents offer a comprehensive overview of the complexities and regulatory pathways for conducting such trials, highlighting the necessity for compliance with the Medical Device Regulation (EU 2017/745, MDR) and the Clinical Trials Regulation (EU 536/2014, CTR), as well as with the In Vitro Diagnostic Regulation (EU 2017/746, IVDR).
- Questions 15 and 16 in MDCG 2021-6 Rev. 1 and the detailed guidance in MDCG 2022-10 illuminate the pathway for combined trials involving medical devices and medicinal products. This guidance is crucial for sponsors planning studies that bridge the gap between medical devices and pharmaceuticals, offering clear directives on navigating combined trials.
- The concept of “combined trial” is further elaborated to include simultaneous investigation of a medicinal product (clinical trial authorized under the CTR) and an IVD (clinical performance study), subject to the requirements of both the CTR and IVDR.
- Sponsors are encouraged to thoroughly understand and comply with both MDR/IVDR and CTR requirements, ensuring that all aspects of the combined trials are adequately addressed.
Usability Studies
Usability studies are paramount in ensuring that medical devices meet the highest standards of safety and performance through effective user interface design. The MDCG 2021-6 Rev. 1 document, alongside the EN 62366-1:2015 standard, provides comprehensive guidance on when and how usability studies are considered within the scope of clinical investigations under the MDR.
It emphasizes the crucial role of usability studies in integrating user feedback into the device design and development processes. This aligns with the focus of EN 62366-1:2015 on user interface characteristics that foster both safety and user satisfaction, highlighting the importance of these studies in enhancing device usability and overall patient care.
Usability testing evaluates how well users can interact with a device within specified environments, aiming to enhance the user interface to promote performance, safe, and satisfying use.
- Question 17 of MDCG 2021-6 Rev. 1 clarifies when usability studies are regarded as clinical investigations under the MDR. The classification hinges on the study’s scope, purpose, and the extent to which users are exposed to the device.
- Usability testing that exposes users to device-related risks or where poor usability could impact patient or user safety is more likely to fall under the definition of a clinical investigation. Manufacturers must document their rationale for classifying a usability test as outside the scope of a clinical investigation when human subjects are involved.
- Manufacturers should strategically design usability tests to limit human exposure to risks before investigating device performance and safety in clinical investigations.
- Documentation of usability considerations, as part of the technical documentation, is critical. This includes justifying why certain usability tests do not constitute clinical investigations, ensuring compliance with both MDCG 2021-6 Rev. 1 guidance and EN 62366-1:2015 requirements.
Invasive or Burdensome Considerations in MDCG 2021-6 Rev. 1
- Question 13 is particularly relevant for ensuring the ethical conduct and safety of participants in clinical investigations. It delves into what is considered burdensome or invasive, guiding sponsors in designing studies that minimize discomfort or risk to participants. This question is vital for maintaining ethical standards and participant welfare in both medical device and in vitro diagnostic studies under IVDR.
Impact on Medical Device Stakeholders
The MDCG 2021-6 Rev. 1 document significantly influences the medical device sector. It offers pivotal guidance that extends well beyond the regulatory framework to affect various stakeholders involved in the lifecycle of a medical device within the European Union.
Manufacturers and Sponsors
Manufacturers and sponsors find in MDCG 2021-6 Rev. 1 an essential roadmap. This guidance provides clarity on regulatory requirements, helping to streamline clinical investigations, mitigate risks, and shorten the time-to-market for innovative solutions.
- Strategic Planning and Execution: The document outlines regulatory pathways for different types of clinical investigations, facilitating better planning and execution.
- Risk Management: Emphasizes the importance of safety reporting and ethical considerations, aiding in the development of comprehensive risk management strategies.
Competent Authorities and Ethics Committees
Competent authorities and ethics committees are crucial in the regulatory oversight of medical devices. MDCG 2021-6 Rev. 1 enhances their ability to assess and ensure compliance with the MDR, promoting a unified application across the EU.
- Streamlined Review Processes: Provides clear guidelines that support more efficient review and approval processes, contributing to quicker decision-making.
- Enhanced Transparency and Consistency: Promotes transparency and consistency in the review of clinical investigations, bolstering the collaborative effort across Member States.
Research Centers and CROs
Research centers and Contract Research Organizations (CROs) play a vital role in conducting clinical investigations. The document offers them detailed guidance on designing and implementing studies that align with regulatory expectations and scientific rigor.
- Design and Conduct of Studies: Facilitates the incorporation of ethical considerations and safety reporting in study designs, ensuring the generation of reliable and meaningful data.
- Collaboration Enhancement: Aids in fostering collaborations between industry and research entities, ensuring that studies are conducted efficiently and effectively.
Legal Representatives
Legal representatives are instrumental in ensuring that the sponsor’s obligations under the MDR are met, particularly for non-EU sponsors. MDCG 2021-6 Rev. 1 clarifies their roles and responsibilities, ensuring compliance across the board.
- Regulatory Compliance: Guides legal representatives in navigating the MDR requirements, ensuring sponsors fulfill their regulatory duties.
Patients and the General Public
The ultimate beneficiaries of the MDCG 2021-6 Rev. 1 are patients, who gain access to safer and more performance-oriented medical devices.
- Access to Innovative Treatments: Enhances patient access to new and innovative medical devices, improving treatment options and patient care.
- Enhanced Patient Safety: Prioritizes patient safety through rigorous clinical investigation standards.
Conclusion
The MDCG 2021-6 Rev. 1 marks a significant stride in the EU’s approach to medical device regulation. This document is vital for navigating the complexities of the Medical Device Regulation (EU 2017/745, MDR). It offers a roadmap that impacts a wide range of stakeholders, from manufacturers to regulators and researchers.
- Guidance and Collaboration MDCG 2021-6 Rev. 1 details the path for clinical investigations under MDR. It covers regulatory pathways, changes in trials, and usability considerations. This guidance is crucial. It ensures that devices entering the market are both innovative and safe. The document encourages collaboration across the sector, highlighting the shared goal of enhancing patient care.
- Impact Across the Board Manufacturers, competent authorities, ethics committees, and others find value in this guidance. It clarifies MDR compliance, aiding in the efficient development and evaluation of medical devices. The emphasis is on using feedback, ensuring ethical conduct, and strategic planning. This collaborative effort advances medical device safety and innovation.
- Benefiting Patients and the Public Ultimately, patients and the public stand to gain the most. They benefit from safer, more performance-oriented medical devices. The document fosters an environment where patient care is at the forefront. Innovations in device technology directly enhance patient outcomes and treatment options.
- Moving Forward As the regulatory landscape evolves, staying informed and adaptable is key. Stakeholders must use MDCG 2021-6 Rev. 1 insights to meet the MDR’s demands. This commitment to high standards in device development and evaluation will continue to benefit European healthcare.
