VI.App.3.1. Modalities applicable to competent authorities in Member States and to marketing authorisation holders

Location:
VI. Appendix 3

Figure VI.4. Business process map – ICSRs submission in EU by competent authorities in Member States (NCAs) and marketing authorisation holders (MAHs). See steps description in Table VI.6.

Table VI.6. Process description – ICSRs submission in EU by competent authorities in Member States (NCAs) and marketing authorisation holders (MAHs). See process map in Figure VI.4.

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 ICSR. Create an individual case safety report (ICSR). Go to step 2.1. NCA/MAH
2.1 Is ICSR valid? Is the report a valid ICSR in accordance with VI.B.2.?

If no, follow-up on the ICSR as described in VI.App.1.1.

If yes, go to step 3.

 NCA/MAH
3 Is ICSR serious? Is the ICSR serious?

If No go to step 3.1.

If Yes, go to step 4.

 NCA/MAH
3.1 Is ICSR from EEA? Is the ICSR from EEA?

If No go to step 3.2.

If Yes, go to step 4.

 NCA/MAH
3.2 End. The ICSR is not serious and it is not from the EEA. It should not be sent to EV. NCA/MAH
4 Submit ICSR to EV. Submit the 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 frame (15 or 90 days, as applicable). Non-serious non-EEA ICSRs should not be submitted to EV. Go to step 5.

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
5 Message received in EV. Receive the message in the EV. Go to step 6. EMA
6 Technical Validation (EV Business Rules). Every message received in EV is validated against the EudraVigilance Business Rules and an acknowledgement message (ACK) is created specifying whether the message & ICSR(s) therein are correct.

The acknowledgement message is sent to the sender (Go to step 7).

  • E2B(R2) messages will receive an E2B(R2) acknowledgement. – E2B(R3) messages will receive an E2B(R3) acknowledgement.
  • A correct E2B(R2) ICSR will have an E2B(R2) ACK code 01 (ACK_B.1.8).
  • An E2B(R2) ICSR not correct will have an E2B(R2) ACK code 02 (ACK_B.1.8).
  • An E2B(R2) message will receive a transmission acknowledgement code 03 (ACK_A.1.6) if the message is not correctly formatted.
  • A correct E2B(R3) ICSR will have an E2B(R3) ACK code “CA” (ACK.B.r.6).
  • An E2B(R3) ICSR not correct will have an E2B(R3) ACK code “CR” (ACK.B.r.6).
  • An E2B(R3) message will receive a transmission acknowledgement code “AR” (ACK.A.4) if the message is not correctly formatted.
 EMA
7 ACK message sent. The acknowledgement message created in step 6 is transmitted to the sender no later than 2 business days following the receipt of the ICSR.

Go to step 11 for the EMA’s next step.

Go to step 8 for MAH/NCA’s next step

 EMA
8 Receive ACK message. Receive the ACK message.

Associate it with the relevant ICSR and check that it was considered valid. Go to step 9.

 NCA/MAH
9 Is ICSR ACK positive? Is a positive acknowledgement code received for the ICSR?

If yes, go to step 9.1.

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 10 to correct the ICSR.

Neither an ICSR not correct (with an E2B(R2) ACK code 02 or E2B(R3) ACK code “CR”), nor a message not correct (with an E2B(R2) transmission acknowledgement code 03 or E2B(R3) transmission acknowledgement code “AR”) constitute new information.

 NCA/MAH
9.1 End. End the process for this ICSR. Normal follow-up activities should continue and if any follow-up report is received, return to step 1. NCA/MAH
10 Correct ICSR. Correct the ICSR to remove the errors identified in the ACK. Go to step 10.1. NCA/MAH
10.1 Resubmit corrected ICSR. Resubmit the corrected ICSR to EV.

Go back to step 5 for the receipt of the corrected ICSR in EV.

 NCA/MAH
11 Store ICSR in EV. Once the ICSR has been technically validated (step 6) and the acknowledgement message is transmitted to the sender (step 7), the ICSR is stored in the EV. Go to step 12. EMA
12 Was ICSR ACK positive? Did the technical validation of the ICSR in step 6 create a positive ACK code?

If no, perform no further processing on this version of the ICSR and go to step 12.1

If Yes, go to step 13.

 EMA
12.1 Await corrected case. 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 stored in EV (step 11) while waiting for corrected version. Go back to step 5 upon receipt of the corrected ICSR.

 EMA
13 End. The ICSR is now stored in EV.

It is available for signal detection and data quality analyses following duplicate detection and recoding.

If the ICSR occurred in the EU and was transmitted to EV by a MAH, it will be rerouted to the relevant NCA (see VI.App.3.4).

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