Hi Maria,
1. All safety related email communications should be filed to Zone 07 Artifact 07.03.01.
2. Yes, all safety notifications to IRB or IEC and Regulatory are required to be file under 04.03.01 and 03.03.01 respectively.
3. Documents which needs review and approval from RA and EC should be filed under Submission classification. Even other essential notifications rather than safety also need to be filed under Submission.
4. Notification of trial termination artifact should include only end of trial notification correspondence and related documents. Other documents related to other event required to classified as per content.