What is a substantial modification?
A modification will be considered substantial if:
• The modification may have a substantial impact on the safety, health or rights of the subjects
• The modification may have substantial impact on the robustness or reliability of the clinical data generated by the investigation
Further guidance on what may be considered a substantial modification can be found in the EU Commission’s guidance document MDCG 2021-6: Regulation (EU) 2017/745 – Questions & Answers regarding clinical investigation.
How do I submit a notification of a substantial modification?
The notification of the substantial modification should be submitted to NoMA by email to firstname.lastname@example.org, and to REK via the REK-portal
. The notification must be submitted to NoMA and REK on the same day.
What documentation should be submitted?
• Notification form: Fill out the form Clinical investigation – Substantial modification of clinical investigation under Medical Device Regulation (attachment to MDCG 2021-28 Substantial modification of clinical investigation under Medical Device Regulation).
• Modified documents: The modified documents must be submitted in both a clean version and a track changes version to facilitate the assessment of the modification(s).
• Changes to investigator or investigational site: When new investigators or sites are included in the clinical investigation, the sponsor must document that the new investigators or sites can conduct the clinical investigation in accordance with the investigational plan (CIP).
- The competency of the investigator must be documented by his or her CV. This applies to the principal investigator at each site.
- The above also applies if the principal investigator is substituted by a new principal investigator at a previously approved investigational site.
- The suitability of the site must be documented by a certification issued by the person responsible for the investigational site.
When can the modifications be implemented?
The sponsor may implement the notified changes no earlier than 38 days after the notification has been submitted NoMA and REK, unless the notification is rejected, or other feedback is given.
The processing time will be extended by an additional 7 days if there is a need to consult external experts in the assessment of the modification notification. The sponsor will be notified if this is the case.