Substantial modifications to a performance study

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, or
• The modification may have a substantial impact on the robustness or reliability of the data generated by the study.

What documentation should be submitted?

Notification form ​

The notification form Substantial modification of performance study under In Vitro Medical Device Regulation must be completed and signed. 

Modified documents

Documents that are changed due to the planned modification must be submitted in both a clean version and a track changes version.

Changes to investigator or investigational site

If the modification involves new principal investigators or investigation sites, the sponsor must document that new investigators or sites are suitable to conduct the performance study in accordance with the clinical performance study plan (CPSP). 

• The competency of the investigator must be documented by his or her CV. This applies to the principal investigator at each site. 

• ​Suitability of the investigation site shall be documented by a statement from the person in charge of the investigation site. 

How to submit a notifi​cation of a substantial modification?

Until Eudamed is available the notification must be submitted by email to ​​​kki@noma.no​. The subject heading should include "Substantial modification of performance study" and NOMAs case reference number. The email must include the PS-ID and title of the study, and information on the sponsor and contact person.

A separate notification must be sent to the Norwegian Ethics Committees for Clinical Trials on Medicinal Products and Medical Devices (REK KULMU) via the REK-portal. For more information, see REK KULMUs website. The notification must be submitted to NOMA and REK KULMU on the same day. 

When can the modification be implemented?

The sponsor may implement the notified modification no earlier than 38 days after the notification has been received NOMA and REK KULMU, unless:

• NOMA has rejected the notification, or 
• REK KULMU has issued a negative opinion

​The processing time will be extended by an additional 7 days if there is a need to consult experts in the assessment of the notification. The sponsor will be notified if this is the case.​​

Non-substantial modifications

Changes to performance studies that fall outside the category of "substantial modifications" do not require notification to NOMA.

For non-substantial modifications to the documentation mentioned in Chapter I of Annex XIV, the sponsor shall make the updated documentation available, cf. IVDR Article 66 (2). In the absence of Eudamed, NOMA requests that sponsors submit the updated documents by email to kki@noma.no, marked with the NOMA case reference number. We ask for confirmation that the changes have been assessed as non-substantial, cf. IVDR Article 71. It is not necessary to submit updated documentation if the changes are insignificant to the content of the text (e.g., linguistic improvements).

Non-substantial modifications must be notified to the Norwegian Ethics Committees for Clinical Trials on Medicinal Products and Medical Devices (REK KULMU) using the form "Endring og/eller henvendelse" (modification and/or notification) in the REK portal. For more information, see REK KULMUs website.