Authorisation Process for Substantial Modifications in Clinical Investigations in Denmark

1. Definition of Substantial Modification

Substantial modifications are those likely to have a substantial impact on the safety, health or rights of subjects, or on the robustness or reliability of the clinical data generated. Source: Danish Medicines Agency Substantial Modifications Application Page https://laegemiddelstyrelsen.dk/en/devices/clinical-investigations/application-for-authorisation-of-substantial-modifications/

2. Requirement for Authorisation

Substantial modifications must be authorised by the Danish Medicines Agency before implementation. The ethics committee must complete its assessment before the Agency decides. Source: Danish Medicines Agency Substantial Modifications Application Page https://laegemiddelstyrelsen.dk/en/devices/clinical-investigations/application-for-authorisation-of-substantial-modifications/

3. Submission Process

Applications are submitted by email to the Danish Medicines Agency and the relevant ethics committee (Regional Research Ethics Committee for investigations authorised before 26 May 2021; Medical Research Ethics Committees for those authorised after). Include a description of the modification with rationale and updated documents (e.g., investigation plan, investigator’s brochure, participant information) with changes clearly marked (e.g., tracked changes). Source: Danish Medicines Agency Substantial Modifications Application Page https://laegemiddelstyrelsen.dk/en/devices/clinical-investigations/application-for-authorisation-of-substantial-modifications/

4. Required Information

Provide details on whether the investigation is ongoing, number of included subjects, and how the modification may affect subject safety or data reliability. Use specific application forms depending on authorisation date. Source: Danish Medicines Agency Substantial Modifications Application Page https://laegemiddelstyrelsen.dk/en/devices/clinical-investigations/application-for-authorisation-of-substantial-modifications/

5. Non-Substantial Modifications

For minor modifications, continuously submit new documents to the Danish Medicines Agency for information only. Source: Danish Medicines Agency Substantial Modifications Application Page https://laegemiddelstyrelsen.dk/en/devices/clinical-investigations/application-for-authorisation-of-substantial-modifications/

6. Timelines and Safety

The Agency has 38 days to assess. If safety risks arise, sponsors must immediately notify the Agency and take protective measures. Source: Danish Medicines Agency Substantial Modifications Application Page https://laegemiddelstyrelsen.dk/en/devices/clinical-investigations/application-for-authorisation-of-substantial-modifications/

7. Guidance

Refer to MDCG 2021-6 Rev. 1 for questions and answers on clinical investigations under MDR. Source: Danish Medicines Agency Substantial Modifications Application Page https://laegemiddelstyrelsen.dk/en/devices/clinical-investigations/application-for-authorisation-of-substantial-modifications/