MDR requirements for pre-market clinical investigations – General considerations

The MDR sets out very detailed requirements regarding clinical investigations in comparison with the Directives 

MDR article 2(45) defines ‘clinical investigation’ as:

‘any systematic investigation involving one or more human subjects, undertaken to assess the safety or performance of a device.’

A pre-market clinical investigation, namely, a clinical investigation with a device that has not yet been CE marked, will need to comply with the MDD, AIMDD, or the MDR. When clinical investigations are conducted under the MDR, they will also need to comply with any applicable common specifications, defined in MDR Article 2(71) as:

‘a set of technical and/or clinical requirements, other than a standard, that provides a means of complying with the legal obligations applicable to a device, process or system.’

A clinical investigation will also need to comply with any applicable requirements of the national competent authority/authorities and ethics committee(s). Applicable European harmonized standards should be followed and other relevant international standards and European and national guidance documents should be taken into consideration. It is also important that sponsors are fully versed in the state of the art in medical practice related to the device technology involved, including relevant practice guidelines or other device-related guidance. This is important because the demonstration of compliance of a device with MDR safety and clinical performance requirements, for example, those specified in general safety and performance requirement (GSPR 1), must take account of the generally acknowledged state of the art.

The MDR sets out very detailed requirements regarding clinical investigations in comparison with the Directives. MDR Articles 62 through 80 address:

• general requirements regarding clinical investigations conducted to demonstrate conformity of devices
• informed consent
• clinical investigations on subjects requiring special consideration
• application process and assessment by Member States
• conduct of the clinical investigation
• electronic system on clinical investigations and other aspects

Implementing acts by the European Commission, intended to provide additional details, are covered in MDR Article 81. MDR Annex XV, Clinical Investigations, consists of three chapters: Chapter 1, General Requirements; Chapter 2, Documentation Regarding the Application for Clinical Investigation; and Chapter 3, Other Obligations of the Sponsor. The AIMDD and MDD each specify requirements regarding clinical investigations in only one article (AIMDD Article 10 and MDD Article 15), and parts of two annexes (AIMDD Annexes 6 and 7 and MDD Annexes VIII and X).

In spite of the detailed requirements included in the MDR, manufacturers with experience in conducting clinical investigations may find that many of these requirements are familiar. This is because similar requirements and procedures are described in the European harmonized standard, BS EN ISO 14155:2011, Clinical investigation of medical devices for human subjects – Good clinical practice, and in various European guidance documents related to clinical investigation. The European guidance documents are:

• MEDDEV 2.7/4 on the need for, and general principles of, clinical investigations
• MEDDEV 2.7/2 Rev 2 on clinical investigation validation and assessment by competent authorities
• MEDDEV 2.7/3 Rev. 3 on serious adverse event (SAE) reporting

In fact, the requirements in the MDR regarding clinical investigations were intentionally based on BS EN ISO 14155:2011 (see MDR ‘Whereas’ statement #64) and on the European guidance documents listed above.

It is important to note that BS EN ISO 14155:2011 has been revised. During its revision every effort was made to avoid conflicts with the MDR, while meeting international needs. The revised standard is expected to become a European harmonized standard regarding compliance with MDR clinical investigation requirements. Due to a delay in the harmonization process however, it is not possible to predict the timing of harmonization.

Regardless of its harmonization status, manufacturers are advised to purchase the standard as soon as it is available and implement all applicable procedures and practices, as it will reflect the state of the art regarding good clinical practice (GCP) for medical device clinical investigations. Any references made in this blog post to the revised standard apply to the Final Draft of ISO/FDIS 14155 in which only editorial changes can be made before publication of the final standard.

The European Commission is in the process of issuing guidance documents to aid in complying with the MDR, including clinical investigation requirements which will be available on the European Commission website.

This is an excerpt from the BSI medical devices white paper: Medical device clinical investigations – What’s new under the MDR? To browse our collection of medical device white papers, please visit the Insight page on the Compliance Navigator website.