The MDCG issued new guidance on the minimum contents expected in an Investigator’s Brochure. It is available: HERE
An editable Word version of MDCG 2024-5, Appendix A is available: HERE
The Investigator’s Brochure (IB) is a required element of a clinical trial application.
The EU MDR’s requirements are outlined under Annex XV (‘Clinical Investigations’), Chapter II (‘Documentation regarding the application for clinical investigation’), Section 2 (‘Investigator’s Brochure’). Further, the preparer should also consider ISO 14155:2020, Clinical investigation of medical devices for human subjects – Good clinical practice.
MDCG 2024-5 provides more detail on the expected minimum contents, and overall structure for the IB. “Brochure” is a bit of a misnomer, as the IB and its attachments can be a fairly extensive document.
Please refer to the guidance document for complete details, including a glossary of abbreviations.
The first few pages should contain:
This section should include the below (as applicable):
Include the manufacturer’s instructions, information to be placed on the label (to the extent possible), implant card, if applicable, and information relating to any relevant training required, plus plans for training if applicable.
Sponsor should verify local language requirements for the labeling and instructions for use.
Include a summary of pre-clinical testing, together with an evaluation of the results of such testing. The data should justify its use on/in human subjects.
As the investigational device must conform to the MDR’s Annex I General Safety and Performance Requirements (GSPRs), this may include technical and biological safety testing, pre-clinical evaluation, and provisions in the field of occupational safety and accident prevention. If any aspects of pre-clinical testing have not been completed prior to the clinical investigation application, it should be highlighted and justified.
See the MDCG guidance for how the summarized information could be provided. As well, further detail on minimum testing expectations, e.g., on performance, reliability, interoperability and compatibility, usability, mechanical, electrical safety and electromagnetic compatibility, biocompatibility and biological safety, software verification and validation, cybersecurity, etc.
Include existing data, such as:
Include a summary of the benefit-risk analysis and risk management, including known or foreseeable risks, undesirable side-effects, contraindications, and warnings. Further, an assessment of anticipated frequency of occurrence of serious adverse events and serious adverse device effects.
If the investigational device is already CE Marked and the investigation is outside of the CE Marking’s intended purpose, ensure that 1) any differences in use and new risks are appropriately addressed, and 2) are clearly described in the Instigator’s Brochure.
See the MDCG guidance for more detail on risk management expectations, including recommendations to refer to ISO 14971:2019, ISO/TC 24971:2020, and Annex H in ISO 14155:2020.
Include detailed information on the medicinal substance or on the tissues, cells, or their derivatives. Readers are recommended to consult with the European Medicines Agency (EMA) guidance documents on Investigational Medicinal Product Dossiers.
Include an overview of which GSPRs apply to the investigational device and a brief justification for any that are not applicable. Further, provide objective evidence on how compliance to each applicable GSPR was achieved. This can include any standards and common specifications applied.
If any GSPRs have not yet been met, but will be covered by the investigation, 1) clearly identify them and 2) indicate how every precaution has been taken to protect the health and safety of the subjects and other users.
This will ideally be presented in checklist format, such as the one provided in MDCG 2021-8. Note that MDCG 2021-8 also includes the MDR clinical investigation application/notification form and Appendix of supporting documents that should be attached (such as the Investigator’s Brochure).
Include a detailed description of the clinical procedures and diagnostic tests used in the course of the clinical investigation. It should particularly highlight and address any deviations from normal clinical practice, and describe what would be considered normal clinical practice as a baseline.
Further, specify any other devices or medicinal products to be used in combination with the investigation device and provide their regulatory status.
This is a cross-reference against each requirement under MDR Annex XV, Chapter II ‘Documentation regarding the application for clinical investigation’. By using this checklist, the sponsor can better ensure they have addressed each section.
The MDCG guidance contains a PDF copy (pages 30-34). An editable Word version of Appendix A is also available: HERE
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