MDCG Guidance on Substantial Modification of Clinical Investigation

by | Dec 15, 2021 | Clinical Writing

The latest MDCG Guidance (2021-28) explained

Earlier this month, December 2021, the MDCG published a new guidance document alongside an accompanying template. These documents are directed towards the sponsors of a clinical investigation and provide information as to how to report the occurrence of a substantial modification within a clinical investigation, whilst retaining conformance with the MDR 2017/745.

A clinical investigation, as described in the MDR 2017/745, is;

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

Clinical investigations can either be conducted prior to a device being CE marked for the first time (pre-market), or over a period of time when a device is actually on the market (post-market). Pre-market clinical investigations are usually conducted to provide an initial demonstration of the claimed performance and safety characteristics of a device. A post-market clinical investigation however, may either be conducted if a current device has been modified to provide new indications, or, if the post-market surveillance system of a device identifies a risk which requires further investigation.

Not all devices require clinical investigations to evaluate their performance or safety profiles. Many lower risk and lower classification devices are able to use the currently available scientific literature, alongside the data collected from pre-clinical studies (tests that don’t involve human subjects). Clinical investigations are expensive to conduct and can take a number of years to complete; in instances whereby concerns arise regarding participant safety, or the data produced by the investigation may not be as usable as once thought, a sponsor may have to introduce a substantial modification to the clinical investigation.

The contents of the newly released MDCG 2021-28 guidance firstly define the term ‘substantial modification’ as modifications;

 ‘that are likely to have a substantial impact on the safety, health or rights of the subjects or on the robustness or reliability of the clinical data generated by the investigation

The guidance also states that any modifications recognised as being substantial have a one week period, whereby the sponsor of the investigation will be required to notify the relevant Member State, and that this notification should be ‘by means of the same electronic system’. The latter part of this statement relates to the EUDAMED electronic database, which is currently incomplete, and therefore an alternative template document has been provided to serve this purpose in the meantime. The guidance also references documents MDCG 2021-20 (Instructions for generating CIV-ID for MDR Clinical Investigations) and MDCG 2021-08 (Clinical investigation application/notification documents), as resources available for sponsors to help support clinical investigation procedures with respect to the MDR. The MDCG 2021-08 guidance is specifically referenced to be a document in which sponsors should use to aid them in the recognition as to which documents will require adaptation, following the clinical investigation modification. It should also be noted that although the use of the provided template is encouraged by the MDCG, additional national requirements may be absent, as these may vary dependent on the Member State in which the clinical investigation has been conducted or planned.

If you need regulatory advice when declaring a substantial modification to your clinical investigation, or anything else, just get in touch with IMed at or by telephone on 01295 724286.

Jacob Tyson

Jacob Tyson

Medical Writer

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