MDCG 2024-5: Guidance on the Investigator’s Brochure Explained

The Medical Device Coordination Group (MDCG) 2024-5 document provides guidance on the content of the Investigator's Brochure (IB) for clinical investigations of medical devices. The IB is a required document when submitting an application for a clinical investigation under Article 70(1) of Regulation 2017/745 (EU MDR).

The investigator's brochure ensures that investigators have access to comprehensive technical and clinical data about the investigational device before and during the study.

MDCG 2024-5 is aimed at helping sponsors develop their IB in accordance with both EU MDR and ISO 14155:2020, the international standard on the clinical investigation of medical devices. You can think of this guidance as an attempt to reconcile what the standard recommends with regulatory requirements in EU MDR.

This article summarizes the recommendations of the guidance and will act as an overview of what goes into the IB to help you get your bearings as you begin putting it together.

Here’s what goes into the investigator’s brochure.

BONUS RESOURCE: Click here to download a free checklist that will help ensure the minimum IB requirements for validation of the application per 
article 70 of the EU MDR.

Administrative Details

The IB should be clearly identified, including the name of the investigational device, document reference number, version, and date. It must include the sponsor's and manufacturer's contact details, a confidentiality statement, a summary of revision history, and a table of contents.

Investigational Device Information

In this section, you’ll need to include an identification and description of the device, its intended purpose, the risk classification and the applicable classification rule you used to come to that conclusion, as well as the design and manufacturing of the device and reference to previous and similar generations of the device.

• Identification of the Device: The IB should explain if multiple names are used for the same device and ensure consistent terminology throughout the documentation.
  
  
• Intended Purpose: The intended purpose must be stated clearly, specifying indications, contraindications, target patient groups, and intended users. Any differences between the clinical investigation's intended purpose and the market's intended purpose should be noted.
  
  
• Intended Clinical Performance: Here, you’ll describe the clinical performance the device aims to achieve, explaining how the device's technical and functional characteristics lead to clinical benefits. For products without an intended medical purpose, performance demonstration is required.
  
  
• Qualification and Classification: In this section, you’ll need to provide a rationale for the device's qualification as a medical device and its risk class that aligns with MDR definitions and classifications. For borderline products, you’ll need to include the scientific rationale for device qualification.
  
  
• Literature and Evaluation Supporting the Design and Intended Use: This section is a summary of the literature, previous research, and evaluations supporting the device's design and intended use.
  
  
• General Description of the Device: The investigator’s brochure must contain a description of the device's design, including key functional elements, materials used, and technical specifications. This should include diagrams, photographs, and drawings along with a sufficient written explanation of them.
  
  
• Summary of Relevant Manufacturing Processes: Here, you’ll provide a summary of manufacturing processes and quality controls, ensuring the device's quality and robustness.
  
  
• Reference to Previous and Similar Generations of the Device: In this section, you’ll give an overview of previous and similar versions of the device, focusing on clinical use and late-stage development.
  
  
• Overview of Identified Equivalent or Similar Devices: The sponsor should provide an overview of equivalent or similar devices available in the market, highlighting the investigational device's novelty.

Labels and Instructions for Use

Your investigator’s brochure will need to include instructions for installation, maintenance, maintaining hygienic standards, and using the device, including storage and handling requirements. You’ll also include any available information that will be placed on the label and its instructions for use. Be sure to check national legislation, as some countries may require labeling and instructions for use (IFU) to be in a national language.

• Instructions for Use: For non-CE-marked devices, you’ll need to include detailed instructions for use in this section. For CE-marked devices used outside their intended purpose, both the CE-marked IFU and study-specific IFU should be provided.
• Labels: Labels should include information required for market placement, including "exclusively for clinical investigation" for investigational devices.
• Training: Here, you’ll describe any training needs and plans for said training.
• Implant Card: For implantable devices, a study implant card should be provided for patient safety, including detailed content as per MDR and MDCG guidance.

Pre-clinical Evaluation

In this portion of the investigator’s brochure, you’ll need to include a pre-clinical evaluation based on any relevant pre-clinical testing and experimental data. That could include a host of different tests, such as in-design calculations, in vitro tests, ex vivo tests, animal tests, electrical or mechanical tests, evaluation of biocompatibility, and software verification and validation.

• General Recommendations: Your pre-clinical tests must be completed before the clinical investigation application, supporting the planned device use. If there is a situation where some aspects of pre-clinical testing have not been completed prior to the clinical investigation, you’ll need to clearly highlight that fact and justify it. The IB should include a summary of pre-clinical testing and evaluations.
  
  
• Specific Recommendations: Your IB should detail performance, reliability, interoperability, and compatibility tests, usability tests, and device-specific tests (mechanical, electrical safety, biocompatibility, software verification, and cybersecurity).

BONUS RESOURCE: Click here to download a free checklist that will help ensure you include the minimum IB requirements for validation of the application per 
article 70 of the EU MDR.

Existing Clinical Data

Your IB should include existing clinical data from literature and previous investigations related to the device's safety, performance, and clinical benefits. This includes data on equivalent or similar devices and summaries of ongoing and completed investigations.

Risk Management of the Investigational Device

Here, you’ll need to provide a summary of the benefit-risk analysis and risk management, detailing known and foreseeable risks, side-effects, contraindications, and warnings. The risk management process should be described, including risk analysis, evaluation, and control measures.

Anticipated Serious Adverse Events (SAEs) and Serious Adverse Device Effects (SADEs): The IB should assess the anticipated frequency of SAEs and SADEs based on internal risk management documents, presenting the outcomes in a tabular format. This assessment helps determine the clinical investigation's risk-benefit ratio.

Devices Incorporating Medicinal Substances or Biological Materials

For devices incorporating medicinal substances, human blood or plasma derivatives, or non-viable tissues or cells of human or animal origin, the IB should provide detailed information on quality, safety, and compliance with relevant requirements.

• Quality Aspects: Sponsors should provide detailed information on the quality aspects required for competent authority assessment, including manufacturing process, specifications, and stability data.
• Information on Incorporation of Medicinal Substances: The IB must include sufficient information to evaluate the quality of the medicinal substance after incorporation into the device, detailing the incorporation process, quality and purpose of excipients, and the complete composition of the final device.

Fulfillment of General Safety and Performance Requirements

Your IB should list how the investigational device meets the relevant General Safety and Performance Requirements (GSPR) set out in Annex I of the MDR, including applied standards and evidence of conformance.

Procedures

The IB should include a detailed description of the clinical procedures and diagnostic tests used in the clinical investigation, highlighting any deviations from normal clinical practice.

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