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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.

Essential Clinical Investigation Document EU MDR requirements ISO 14155:2020 requirements Guidance MDCG
Clinical Investigation Plan (CIP) Annex XV, Chapter II, Section 3 Annex A (normative) MDCG 2024-3, March 2024
Investigator’s Brochure Annex XV, Chapter II, Section 2 Annex B (normative) MDCG 2024-5, April 2024

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?

NAMSA can assist you at any stage of the clinical development process, from conception to approval, and in various geographical areas. If you are interested in speaking with us about global regulatory strategies, please Contact Us, or learn more about our Clinical and Regulatory experts here.

Sara Finocchietti, MEng, PhD

Sara Finocchietti has 15 years of experience in the medical device industry, having lived in multiple European countries and Japan. Her career started in public research developing innovative medical devices as well as providing clinical and regulatory strategy for market access in Europe. Her previous experiences include working as a Clinical Affairs Manager at a French manufacturer with a full orthopedic portfolio, defining the strategy to transition to the EU's Medical Device Regulation (MDR). Sara has a keen interest in new technologies and innovation. She has extensive experience working within cross-functional and cross-cultural teams.

Ariadna Navarro

Dr. Ariadna Navarro has a strong scientific background with a PhD in Cardiovascular Sciences and close to ten years of experience in preclinical and clinical research. During her academic career, she collaborated with In Vitro Diagnostic (IVD) manufacturers in the design of strategies and the set up of in vitro techniques to diagnose several cardiovascular and neurological disorders. Dr. Navarro’s medical device industry experience includes working as Clinical Research Scientist and Clinical Study Manager, gaining thorough knowledge in the design, set-up and conduct of clinical investigations according to ICH/GCP guidelines, ISO 14155 and ISO 20916. Ariadna has also developed a strong experience in Regulatory Affairs and Quality Assurance, and she has expert competence on the European regulatory landscape (MDR 2017/745, IVDR 2017/746 and the MEDDEV/MDCG guidance documents). She is a certified ISO 13485 Lead Auditor with experience in setting up medical device quality management system standards aiming to support manufacturers placing and maintain their devices in the market.