VI. Appendix 4 Submission of ICSRs to the World Health Organization (WHO)
Figure VI.6. Business process map – Submission of ICSRs to the World Health Organization (WHO) Collaborating Centre for International Drug Monitoring. See steps description in Table VI.10.
Table VI.10. Process description – Submission of ICSRs to the World Health Organization (WHO) Collaborating Centre for International Drug Monitoring. See process map in Figure VI.6.
| No. | Step | Description | Responsible Organisation |
| 1 | Start. | Receipt by the NCA or the MAH of a report of suspected adverse reaction related to a medicinal product (ADR report). Go to step 2. | NCA/MAH |
| 2 | Create and record ICSR. | Create an individual case safety report (ICSR). Go to step 3. | NCA/MAH |
| 3 | Submit valid ICSR to EV. | Submit the valid ICSR (EEA and non-EEA serious, and EEA non-serious) to EudraVigilance (EV) in ICHE2B(R2/R3) format as an XML message within the relevant time frames (15 or 90 days, as applicable). Non-serious non-EEA ICSRs should not be submitted to EV. Go to step 4.
Proceed as outlined in VI.App.1.1. if the ICSR is not valid. See guidance in the EU Individual Case Safety Report (ICSR) Implementation Guide (EMA/51938/2013) in case of system failure in safety message generation, submission, receipt, processing and rerouting |
NCA/MAH |
| 4 | Message received in EV. | Receive the message in EV. Go to step 5. | EMA |
| 5 | Technical Validation (EV Business Rules). | Every message that is received in EV is validated against the EudraVigilance Business Rules and an Acknowledgement message (ACK) is created specifying whether the message and the ICSR(s) therein are valid.
The acknowledgement message is sent to the sender (step 6).
|
EMA |
| 6 | ACK message sent. | The acknowledgement message created in step 5 is transmitted to the sender no later than 2 business days following the receipt of the ICSR.
Go to step 10 for EMA’s next step. Go to step 7 for NCA/MAH’s next step. |
EMA |
| 7 | Receive ACK message. | Receive the ACK message. Associate it with the relevant ICSR and check to ensure that the ICSR was considered valid. | NCA/MAH |
| 8 | Is ICSR ACK positive? | Is a positive acknowledgement code received for the ICSR?
If Yes, go to step 8.1. If no, then the regulatory timeline clock has not stopped and the ICSR should be corrected and retransmitted to EV within the relevant regulatory timelines. Day 0 remains as the day that the first information was received. Go to step 9 to correct the ICSR. Neither an ICSR not correct (E2B(R2) ACK code 02 or E2B(R3) ACK code “CR”), nor a message not correct (E2B(R2) transmission acknowledgement code 03 or E2B(R3) transmission acknowledgement code “AR”) constitute new information. |
NCA/MAH |
| 8.1 | End. | End the process of transmitting this version of the ICSR to EV. Normal follow-up activities should continue and if any follow-up is received, return to step 1. | NCA/MAH |
| 9 | Correct ICSR. | Correct the ICSR to remove the errors identified in the. Go to step 9.1. | NCA/MAH |
| 9.1 | Resubmit corrected ICSR. | Resubmit the corrected ICSR to EV.
Go back to step 4 for the receipt of the corrected ICSR in EV. |
NCA/MAH |
| 10 | ICSR stored in EV. | Once the ICSR has been technically validated (step 5) and the acknowledgement message is transmitted to the MAH (step 6), the ICSR is stored in EV. Go to step 11. | EMA |
| 11 | Was ICSR ACK positive? | Did the technical validation of the ICSR in step 5 create a positive ACK code? If no, perform no further processing on this version of the ICSR and go to step 11.1. If Yes, go to step 12. | EMA |
| 11.1 | Await corrected ICSR. | The sender should correct every ICSR with an error ACK and retransmit it within the appropriate regulatory timelines. EMA periodically assesses all ICSRs with an error ACK for which a corrected version has not been transmitted and contact the sender to inform of these missing corrected ICSRs. If a sender fails to correct the ICSRs, this information is incorporated into data quality assessments and the appropriate committee is informed.
The ICSR is stored in EV (step 10) while waiting for a corrected version. Go back to step 4 upon receipt of the corrected ICSR. |
EMA |
| 12 | Is ICSR from EEA? | Once a week, for every message that has passed the technical validation, the ICSRs therein are assessed to determine the country where the reaction occurred for regulatory reporting purposes.
Is the ICSR from EEA? If Yes, go to step 13. If No, go to step 12.1. |
EMA |
| 12.1 | EMA | The ICSR is now stored in EV. It is available for signal detection and data quality analyses following duplicate detection and recoding. | EMA |
| 13 | EEA ICSR processing. | Prior to sending the ICSRs to the World Health Organization (WHO) Collaborating Centre for International Drug Monitoring, the ICSRs occurring in the EEA are extracted in line with the EudraVigilance Access Policy for Medicines for Human Use64 . Go to step 14. | EMA |
| 14 | ICSRs sent to WHO. | The ICSRs are sent through the VigiBase API. Go to step 15. | EMA |
| 15 | Message received by WHO. | The submitted message with the EEA ICSRs is received by WHO Collaborating Centre. A Message ID for each submitted file is created and sent back to EMA. Go to step 16. | WHO |
| 16 | Technical Validation. | Technical validation is performed on the submitted ICSRs. A status code is recorded for each message. Go to step 17. | WHO |
| 17 | Status code sent to EMA. | The message status code created in step 16 is transmitted to EMA with the corresponding Message ID. Go to step 18. | WHO |
| 18 | ICSRs stored in WHO database. | Once the ICSRs have been validated, they are stored in the WHO database. Go to step 19. | WHO |
| 19 | Was status code positive? | Did the technical validation in step 16 create a positive status code?
If no, go to step 19.1. If yes, go to step 20 |
WHO |
| 19.1 | Await corrective action. | WHO UMC is contacted by EMA to resolve the technical issues and the message is retransmitted if needed.
ICSRs are stored in WHO database (step 18 while waiting for corrected version). Go back to step 15 upon receipt of the corrected ICSRs. |
WHO |
| 20 | End. | ICSRs are now stored in the WHO Collaborating Centre’s database and are available for signal detection. | WHO |