The article highlights the key points related to the information the Investigator’s Brochure should contain in order to meet the relevant regulatory requirements.
Table of content
The Medical Device Coordination Group (MDCG), an advisory body focused on further improvement of the medical device regulatory framework, has published a guidance document dedicated to the content of the Investigator’s Brochure for clinical investigations of medical devices.
The document provides an overview of the regulatory requirements set forth under the existing legal framework, as well as additional clarifications and recommendations to be taken into consideration by medical device manufacturers, study sponsors, and other parties involved in operations with medical devices intended to be marketed and used in the EU.
Introduction to Investigator’s Brochure (IB)
First of all, the MDCG mentions that when submitting a comprehensive application for a clinical investigation, as per Article 70(1) of the MDR, a responsible party should also provide the relevant documentation specified in Chapter II of Annex XV, with the Investigator’s Brochure (IB) being a crucial component thereto. This entails providing investigators access to technical and clinical data concerning the device under investigation.
The IB clarifies the device’s intended purpose, design, underlying scientific principles, and existing evidence of safety and functionality. The present document issued by the MDCG guides sponsors in IB development, aligning with MDR and ISO 14155:2020, drawing from regulatory requirements and authority insights.
The document also emphasizes the importance of communicating information related to the investigation in a timely manner in order to ensure compliance with the respective regulatory requirements.
Content of the Investigator’s Brochure
The document further describes the key aspects to be addressed in the IB in order to ensure completeness of the information it should contain for the study investigators to be properly informed.
According to the guidance, the IB’s initial pages should provide for clear identification, encompassing the device’s name, document reference, version, confidentiality statement, revision history, and a table of contents. Vital contact information for the sponsor and device manufacturer, if distinct, should also be provided. The MDCG additionally emphasizes the importance of proper numbering to facilitate document navigation and referencing.
Apart from the general information, the IB should also contain comprehensive information about the investigational device in question including, inter alia, the following aspects:
- Identification and Description: In this regard, the MDCG expects consistency in terminology when referencing the device. Variations in nomenclature should be clarified to prevent confusion across study documents.
- Intended Purpose: The IB should describe the device’s intended purpose, encompassing indications, contra-indications, target patient groups, and intended users. Any disparities between the investigational and market-intended purposes are to be delineated, especially concerning CE-marked devices.
- Intended Clinical Performance: Clinical performance delineation describes how the device achieves its intended purpose, correlating with manufacturer claims. The IB outlines clinical benefits, encompassing measurable patient outcomes and diagnostic efficacy, crucial for assessing device efficacy.
- Qualification and Classification: The rationale supporting device qualification as per regulatory definitions should be provided, alongside risk classification alignment with Annex VIII of the MDR. It is also explicitly stated that for borderline products, clarity on device qualification and alignment with regulatory guidelines is important. In cases of combined device and medicinal product studies, the regulatory status for both components should be detailed.
- Literature and Evaluation: The IB should also contain a summative overview of supporting literature, prior research, and evaluations validating the device’s design and intended use, bolstering the rationale behind its investigation.
Development of Investigator’s Brochure
The present MDCG guidance also clarifies the key points to be taken into consideration when developing the IB in order to ensure compliance with the regulatory requirements set forth under the existing legal framework.
- Checklist Adherence: Prior to submission, sponsors are advised to utilize the checklist in Appendix A to ensure IB compliance with Article 70 of the MDR. The inclusion of the completed checklist alongside the IB facilitates the validation of the application.
- Regulatory Compliance: Sponsors are encouraged to familiarize themselves with relevant regulations and standards, including the MDR and ISO 14155:2020, to ensure IB adherence to stipulated guidelines. Thorough understanding aids in comprehensive IB development, minimizing potential queries during regulatory assessment.
- Accessibility and Clarity: The IB should be accessible, concise, and without promotional content, fostering unbiased assessment by potential investigators and site teams. Information presentation should be clear and precise, enabling informed benefit-risk analysis and ensuring safe use of the device.
Updating and Notification Protocols
As mentioned before, it is visually important to ensure all the material updates regarding the device itself of the steps to be taken are communicated to the parties involved without undue delay, as this could impact the safety of study participants/patients, or affect the accuracy and reliability of study results.
- Timely Information Dissemination: Any updates or newly available information pertinent to the IB must be promptly communicated to investigators, facilitating informed decision-making and adherence to evolving regulatory standards.
- Notification Procedures: In accordance with the applicable regulatory requirements, sponsors are obliged to notify concerned member states within one week of IB updates, ensuring regulatory transparency and accountability. Changes to the IB should be clearly delineated for easy identification and comprehension.
Conclusion
In summary, the present guidance document developed by the MDCG emphasizes the pivotal role of the Investigator’s Brochure in facilitating regulatory compliance and ensuring the safety and efficacy of investigational devices. By adhering to outlined protocols and incorporating requisite information, sponsors can streamline the application review process, fostering efficient assessment by competent authorities. Furthermore, continuous adherence to regulatory updates and transparent communication protocols contributes to the integrity of clinical investigations, ultimately benefiting patient care and public health.
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