VI.App.3.4. Rerouting to competent authorities in Member States of ICSRs submitted to EudraVigilance by marketing authorisation holders
Figure VI.5. Business process map – Rerouting to competent authorities in Member States (NCAs) of ICSRs submitted to EudraVigilance by marketing authorisation holders (MAHs). See steps description in Table VI.9.
Table VI.9. Process description – Rerouting to competent authorities in Member States (NCAs) of ICSRs submitted to EudraVigilance by marketing authorisation holders (MAHs). See process map in Figure VI.5.
| No. | Step | Description | Responsible Organisation |
|---|---|---|---|
| 1 | Start. | Receipt by the MAH of a report of suspected adverse reaction related to a medicinal product (ADR report). Go to step 2. | MAH |
| 2 | Create ICSR. | Create an individual case safety report (ICSR). Go to step 3. | 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 the 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 MAH (Go to step 6).
|
EMA |
| 6 | ACK message sent. | The acknowledgement message created in step 5 is transmitted to the MAH 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 MAH’s next step. |
EMA |
| 7 | Receive ACK message. | Receive the ACK message. Associate it with the relevant ICSR and check to ensure that it was considered valid. Go to step 8. | 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. |
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. | MAH |
| 9 | Correct ICSR. | Correct the ICSR to remove the errors identified in the ACK. Go to step 9.1. | 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. |
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. ICSR stored in EV (step 10) while waiting for corrected version. Go back to step 4 upon receipt of the corrected ICSR. |
EMA |
| 12 | Is ICSR from EEA? | Whenever a message has passed the technical validation (step 11), the ICSRs therein are immediately assessed to determine the primary source country 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 | End. | 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 for rerouting. | The ICSRs occurring in the EEA are extracted from the message for processing prior to retransmission to the relevant NCA.
For the retransmission of E2B(R2) messages the ‘Message sender identifier’ (ICH E2B(R2) M.1.5) of the sending MAH is inserted in data element ‘Sender organisation’ (ICH-E2B(R2) A.3.1.2) prior to retransmission. This is to permit the receiving National Competent Authority (NCA) to unambiguously identify the MAH responsible for transmitting the ICSR to EV. For the retransmission of E2B(R3) messages the data element N.2.r.2 ‘Message sender identifier’ remains unchanged with the MAH identifier. Go to step 14. 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. |
EMA |
| 14 | ICSR sent to relevant NCA. | The ICSR is transmitted to the relevant NCA with no other changes.
Where a Member State has more than one NCA responsible for post-marketing reports, the ICSRs occurring in that Member State are sent to all relevant NCAs. Go to step 15. |
EMA |
| 15 | Message received in NCA database. | Message with EEA ICSRs are received in the relevant NCA database. Go to step 16 | NCA |
| 16 | Technical Validation (EV Business Rules). | Every message should be validated against the EudraVigilance Business Rules (the same business rules as in step 5 and an Acknowledgement message (ACK) is created specifying whether the message and the ICSRs therein are valid.
The acknowledgement message is sent to EV (step 17).
|
NCA |
| 17 | ACK message sent. | The acknowledgement message created in step 16 is transmitted to EV within 2 business days following the receipt of the ICSR. Go to step 18. | NCA |
| 18 | ICSR stored. | The ICSR is stored in the NCA database. Go to step 19. | NCA |
| 19 | Was ICSR ACK positive? | Did the technical validation of the ICSR in step 16 create a positive ACK code?
If no go to step 19.1. If yes go to step 20. |
NCA |
| 19.1 | Await corrective action. | The concerned NCA with negative acknowledgement is contacted by EMA to resolve the technical issues and the message is retransmitted if needed.
The ICSR is stored in the NCA database (step 18 while waiting for a corrected version). Go back to step 15 upon receipt of the corrected ICSR. |
NCA |
| 20 | End. | The ICSR is now stored in the NCA database. It is available for signal detection and data quality analyses. | NCA |