Navigating the New MDCG Guidance Documents on CIP and IB

The Medical Device Coordination Group (MDCG) has recently published two crucial guidance documents for Sponsors conducting clinical investigations under the European Union Medical Device Regulation (MDR): MDCG 2024-3, focusing on the Clinical Investigation Plan (CIP) content and MDCG 2024-5, offering detailed guidance to prepare the Investigator’s Brochure (IB).

These guidance documents were developed by the same MDCG working group, taking into consideration the legal requirements, standard of good clinical practice and feedback from national competent authorities, industry and other relevant stakeholders. While these documents are not legally binding, they are representative of the best practices in the field.

The primary objective of these documents is to aid Sponsors in the development of their CIPs and IBs by outlining detailed expectations for each section. Addressing these expectations contributes to a well-structured CIP and IB, helps anticipate questions from regulatory authorities and supports the successful conduct of clinical investigations.

We will delve into the requirements for CIP and IB, our recommendations for working with the new MDCGs and highlight interesting aspects of these guidance documents.

CIP and IB Requirements

The EU MDR describes the legal requirements for the CIP and IB in Annex XV. This annex also stipulates that Clinical Investigations should be conducted in accordance with good clinical practice. The standard that delineates good clinical practice in clinical investigations with medical devices is ISO 14155:2020.

While adherence to ISO 14155:2020 is not a legal obligation, Sponsors are nonetheless expected to follow this standard when designing and conducting a clinical investigation. Therefore, the EU MDR, in conjunction with ISO 14155:2020, provides the foundation for preparing compliant CIPs and IBs (see Table 1). This synergy ensures the highest standards of clinical practice are maintained, thereby safeguarding the integrity of the clinical investigation process.

Table 1. CIP and IB requirements according to EU MDR and ISO 14155.

How to use MDCGs 2024-3 and 2024-5?

• When preparing Clinical Investigation documentation, Sponsors should review both the MDR and the ISO 14155:2020 standard together with the newly released MDCG guidance documents, which provide more detailed information on each requirement. It is important to note that in the case of discrepancies, the EU MDR requirements take precedence.
• The legal requirements from Sections 2 (IB) and 3 (CIP) of Chapter II in Annex XV of the MDR must be explicitly addressed in the documentation or justified as “not applicable”.
• The MDCGs follow the regulation’s numbering system for easy cross-referencing to legal requirements.
• MDCG 2024-5 includes a checklist that manufacturers can use to ensure the IB meets the minimum requirements for validation of the Clinical Investigation application. Although not provided, a similar checklist would also be helpful for Sponsors when preparing their CIP.
• MDCG 2024-3, on the other hand, provides a template to prepare the Clinical Investigation Plan synopsis.

MDCG 2023-3: Clinical Investigation Plan (CIP)

The Clinical Investigation Plan (CIP) is a critical component of any clinical investigation. It outlines the strategy, objectives, and methodology for evaluating the safety and performance of a medical device.

This MDCG is aligned with Section 3 of Chapter II in Annex XV of the MDR, however, some content is presented in greater detail. For instance:

• If the Sponsor is not the manufacturer, a description of the agreement between the Sponsor and the manufacturer should be included in the CIP.
• Risk factors for health care personnel, family members or caregivers should be considered as well as risks related to the interpretation of study data.
• For CE-marked devices, a summary of the relevant post-market surveillance data should be included for the investigational device as well as comparator, if applicable.
• The study design justification should be based on the conclusions of the clinical evaluation.
• The guidance focuses on describing and maintaining procedures for critical processes within the clinical investigation (i.e. procedures for maintaining a list of participating sites and investigators, subject withdrawal and follow-up, reporting deviations from plans, verifying data accuracy, managing non-substantial modifications, recording and reporting CIP deviations, etc).

Highlights of MDCG 2023-5 Investigator’s Brochure

The Investigator’s Brochure (IB) provides essential information about the investigational device to investigators participating in the clinical study. MDCG 2024-5 offers detailed expectations for creating IBs, ensuring that investigators have the necessary knowledge to conduct the study effectively.

This MDCG is aligned with Section 2 of Chapter II in Annex XV of the MDR. While the IB MDR requirements can be fit in a bit more than one page, the MDCG 2024-5 sections focused on explaining the IBs extend over 20 pages, providing a great level of detail on the IB expectations. :

• Differences in the intended purpose in the clinical investigation vs. the planned intended purpose of the device when it is placed on the market should be stated.
• The IB should describe the device’s intended clinical performance and the mechanisms through which it achieves its intended purpose.
• Training needs should be described in the IB.
• The preclinical evaluation should also consider provisions in the field of occupation safety and accident prevention.
• When possible, information should be provided in tabular format (preclinical tests, clinical investigation summaries, risk management, etc). When referencing an external report, the reference should point to the specific section of interest.
• Specific recommendations are provided for bench tests, both horizontal and vertical. Recommendations are also provided for preclinical model studies, including non-GLP studies.
• Regarding risk management, the IB should indicate what information was used to estimate the risks (e.g., standards, articles, expert assessments, tests and simulations). Moreover, Sponsors should include an anticipated frequency of Serious Adverse Events (SAEs) and Serious Adverse Device Effects (SADEs).

How Can NAMSA Help?

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