Regulatory pathways for clinical investigations
The guidance emphasizes that the sponsor is responsible for determining the correct regulatory pathway for its clinical investigations. It contains a helpful visual overview of the different pathways that are outlined in the MDR:
Modifications to clinical investigations
The MDR provides that if a sponsor wants to modify a clinical investigation and such modification is likely to have a substantial impact on either the safety, health, or rights of the subjects or on the robustness or reliability of the clinical data generated by the investigation, the sponsor must notify the Member State(s) concerned. The guidance helps sponsors determine when modifications are substantial, and its Annex II contains a non-exhaustive list of examples.
Annex II provides specific examples of when the following modifications are “likely” to be considered substantial:
- amendments related to the protocol or subject information,
- amendments related to the benefit/risk of the clinical investigation,
- amendments related to the use of the investigational device,
- amendments related to other information, or
- amendments relating to the manufacturing process
Burdensome or invasive procedures
Furthermore, the document provides helpful guidance on the meaning of “additional procedures which are burdensome or invasive” within the meaning of Article 74(1).
According to this Article, where a clinical investigation is conducted with an already CE-marked device, within the scope of its intended purpose, and where the investigation would subject patients to invasive or burdensome procedures, the sponsor must notify the Member State(s).
In these cases, the guidance provides the following:
- The determination of whether an additional procedure is burdensome is generally determined from the perspective of the person bearing the burden. It may include, inter alia, procedures that may cause pain, discomfort, fear, potential risks or complications/side effects, disturbances of lives and personal activities, or otherwise unpleasant experiences.
- Additional procedures that are invasive include, for example, penetration inside the body through the surface of the body, including through mucous membranes of bodily orifices, or penetration of a body cavity via a bodily orifice.
Transitional period
The guidance sets out that because the clinical investigation module in Eudamed will not be ready by May 26, 2021, sponsors should contact the national competent authorities for additional information, for example on how to submit an application for a clinical investigation under the MDR.
The guidance also clarifies the rules applicable to ongoing clinical investigations conducted in accordance with the Medical Devices Directive.
The guidance provides that these clinical investigations may continue to be conducted after May 26, 2021. However, when the MDR is fully applicable, serious adverse events and device deficiencies occurring during the clinical investigation must be notified to the Member States in accordance with Article 80 of the MDR.
The current version of the MDCG 2021-6 guidance document may be supplemented in due course with further questions and answers.
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Manufacturers of medical devices are advised to review the guidance and familiarize themselves with the new obligations. In particular, the clarifications regarding the transitional rules and the applicable reporting obligations until the clinical investigation module in Eudamed is ready, should help sponsors of clinical investigations navigate the coming months of transition.
