The Medical Device Coordination Group (MDCG) is a regulatory body made up of industry experts appointed by each of the member states of the European Union.

The Investigator’s Brochure (IB) is part of the required documentation of the MDR which states that the investigator shall have access to technical and clinical data regarding the device that is being investigated. This includes the intended purpose(s), design, the basic fundamental scientific principles behind the design and the level of objective evidence already in place, to assure its safety and functionality during the investigation.

This guidance document is intended to support sponsors in developing their IB by describing in greater detail what type of information is expected in the respective IB sections, in order to preempt questions from the competent authorities during the assessment of the clinical investigation application. The guidance is based on the requirements of both the MDR and ISO14155:2020 as well as experience from the competent authorities.

MDCG issues guidance on Investigator’s Brochure

• The guidance states that “the description should be as clear and fundamental as reasonably possibly, not assuming that all intended readers are already experts in the field”.
• The guidance provides a comprehensive list of information that manufacturers should submit to authorities. It covers administrative information, information on the device’s clinical performance, information on device labeling, and a summary of preclinical and clinical information on the device.
• The brochure should include labels and instructions for use, including a manufacturer’s instructions for installation and maintenance, and any storage and handling requirements.
• Sponsors should also submit the results of preclinical testing, including in vitro tests, ex vivo tests, animal tests, as well as the results of clinical data from the scientific literature relating to the device’s safety, performance, clinical benefits to patients, design characteristics and intended purpose of the device and or similar devices.
• Sponsors should also submit an Anticipated Serious Adverse Events (SAEs) and Serious Adverse Device Effects (SADEs), which should be based on internal risk management documents. Manufacturers are also asked to provide detailed information on quality aspects required for the competent authority’s assessment in a separate document.

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:

This section includes an identification and description of the device, its intended purpose, the risk classification and the applicable classification rule used to come to that conclusion, as well as the design and manufacturing of the device and references to previous and similar generations of the device.

• Identification of the device
• Intended purpose
• Intended clinical performance
• Qualification and classification
• Literature and evaluation supporting the design and intended use
• General description of the device
• Summary of relevant manufacturing processes
• Reference to previous and similar generations of the device
• Overview of identified equivalent or similar devices

Labels and Instructions for Use:

Investigator’s brochure will need to include instructions for installation, maintenance, maintaining hygienic standards, and using the device, including storage and handling requirements. And also include any available information that will be placed on the label and its instructions for use.

• Instructions for Use: For non-CE-marked devices, 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, 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, we 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, animal tests, electrical or mechanical tests, evaluation of biocompatibility, and software verification and validation.

Existing Clinical Data:

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, we 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 ADEs): 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.

Conclusion:

The MDCG’s guidance emphasizes the importance of a well-prepared investigator’s brochure to facilitate smooth and compliant clinical investigations. Properly drafted and maintained, the IB is crucial for ensuring that investigators have the information needed to conduct studies safely and effectively, while also meeting regulatory and ethical standards.