VI. Appendix 1 Process for follow-up of ICSRs

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VI.Appendix 1

VI.App.1.1. Follow-up of ICSRs by competent authorities in Member States and marketing authorisation holders

Figure VI.2. Business process map – Follow-up of ICSRs by competent authorities in Member States (NCAs) and marketing authorisation holders (MAHs). See steps description in Table VI.2.

Table VI.2. Process description – Follow-up of ICSRs by competent authorities in Member States (NCAs) and marketing authorisation holders (MAHs). See process map in Figure VI.2.

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) and record it in the pharmacovigilance database. Go to step 2.1 NCA/MAH
2.1 Is ICSR valid? Is the report received from the reporter a valid ICSR
in accordance with VI.B.2.?
If Yes, go to step 3.
If No, go to step 10.		 NCA/MAH
3 ICSR is valid. The report received from the reporter is a valid ICSR.
The clock start (D0) for the submission of the valid
ICSR is the date of receipt of the report (see VI.B.7.
for day zero definition). Go to step 3.1.		 NCA/MAH
3.1 Submit initial ICSR to EV. Submit the initial valid ICSR (EEA and non-EEA serious and EEA non-serious) to EudraVigilance (EV) 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 6.2 for the end of the process for this
ICSR.
Go to step 3.2 for follow-up activity.
NOTE: NCA/MAH can organise the submission of the initial and follow-up report in accordance with the appropriate time frames. If time permits and the follow-up information can be obtained and processed within the initial submission time frame, the NCA/MAH is not required to submit the initial and the follow-up report separately.		 NCA/MAH
3.2 Is follow-up required? Is follow-up with the reporter required for the valid ICSR?
If Yes, go to step 4.
If No, go to step 7.		 NCA/MAH
4 Follow-up is required. The ICSR is valid. Follow-up is necessary to obtain significant missing information for the evaluation of the ICSR. This includes information on the patient age or age group if missing, or the mandatory information on the medicinal product batch number when it is missing and the reaction is suspected to be related to a biological medicinal product [DIR Art 102(e) and IR Art 28 (3)]. With respect to this, it is recommended to specify in the case narrative if information on the batch number has been requested, when it is missing in the initially submitted ICSR. Go to step 4.1. NCA/MAH
4.1 Request information from reporter. Contact the reporter to obtain additional information pertinent to the valid case. (see follow-up guidance in VI.B.3. and VI.C.6.2.2.7.). Go to step 4.2. Note: Stakeholders should define in their SOPs how many attempts to contact the reporter should be made until the follow-up information is obtained (or the follow-up attempts can be ceased). NCA/MAH
4.2 Is follow-up information obtained? Has follow-up information been obtained from the reporter on the ICSR?
If Yes, go to step 5.
If No, go to step 8.		 NCA/MAH
5 Additional information obtained. Additional follow-up information has been obtained from the reporter. Go to step 5.1. NCA/MAH
5.1 Record outcome of follow-up. Record the follow-up information in the pharmacovigilance database. Go to step 5.2. NCA/MAH
5.2 Is new information significant? Determine if the new obtained information is significant enough (see VI.C.6.2.2.7. Subsection a for examples of significant and non-significant information) to be submitted to EV.
If Yes, go to step 6.
If No, go to step 9.		 NCA/MAH
6 New information is significant. The new follow-up information is significant enough to be submitted to EV. Go to step 6.1. NCA/MAH
6.1 Submit follow-up ICSR to EV. Submit the follow-up ICSR (EEA and non-EEA serious and EEA non-serious) with the new information to EV 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 6.2. NCA/MAH
6.2 End. The ICSR is stored in EV for signal detection and data quality analyses following recoding and duplicate detection (see VI.App.6 for ICSRs data quality monitoring in EV, and VI.App.7 for duplicate detection and management). It is also available for rerouting to the relevant NCA (See VI.App.3.4), and for access to MAHs to fulfil their pharmacovigilance activities. Go back to step 1 on the receipt of a new information for the ICSR. NCA/MAH
7 Follow-up is not required. ICSR is valid. Follow-up may be performed as necessary to obtain administrative information not required for the scientific evaluation of the ICSR. Go to step 7.1. NCA/MAH
7.1 End. End of the process for this ICSR. Go back to step 1 on the receipt of a new information for the ICSR. NCA/MAH
8 No information has been obtained. The follow-up with the reporter is unsuccessful and no additional information on the ICSR can be obtained. Go to step 8.1. NCA/MAH
8.1 Record the outcome of follow-up. Record the fact that no further information has been obtained from the reporter. Go to step 8.2. NCA/MAH
8.2 End. End of the process for this ICSR. Go back to step 1 on the receipt of a new information for the ICSR.
Note: when the suspected medicinal product is a biological product and the batch number information is not available in the initially submitted ICSR, a follow-up (or amendment) report should be submitted when no information is received on the missing batch number despite contact attempts with the reporter (see step 4). This should be specified in the narrative and with the nullFlavor ASKU where applicable under ICH-E2B(R3) format.		 NCA/MAH
9 New information os not significant. The new follow-up information is not significant enough to be submitted to EV. Go to step 9.1. NCA/MAH
9.1 End. End of the process for this ICSR. Go back to step 1 on the receipt of a new information for the ICSR. NCA/MAH
10 ICSR is not valid. The report received from the reporter is NOT a valid ICSR in accordance with VI.B.2.. Go to step 10.1. NCA/MAH
10.1 Request missing info from reporter. Request the missing information for the non-valid ICSR from the reporter (see guidance in VI.B.3. and VI.C.6.2.2.7.). Go to step 10.2. NCA/MAH
10.2 Is follow-up information obtained? Is follow-up information obtained from the reporter?
If Yes, go to 11.
If No, go to 13.		 NCA/MAH
11 Follow-up information obtained. Follow-up information has been obtained for the nonvalid ICSR. Go to step 11.1. NCA/MAH
11.1 Record the outcome of follow-up with reported. Record the new follow-up information in the pharmacovigilance database. Go to step 11.2. NCA/MAH
11.2 Is the ICSR valid? Is the ICSR with the new follow-up information valid in accordance with the guidance in VI.B.2.
If Yes, go to 12.
If No, go to 14.		 NCA/MAH
12 ICSR is valid. The ICSR is now valid taking into account the new information obtained from the reporter. The clock start (D0) for the submission of the valid ICSR is the date of receipt of the new information (see VI.B.7. for guidance on day zero).
Go to step 12.1.		 NCA/MAH
12.1 Submit ICSR to EV. Submit the ICSR (EEA and non-EEA serious and EEA non-serious) with the new information to EV 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 12.2.		 NCA/MAH
12.2 End. The ICSR is stored in EV for signal detection and data quality analyses following recoding and duplicate detection (see VI.App.6 for ICSRs data quality monitoring in EV, and VI.App.7 for duplicate detection and management). It is also available for rerouting to the relevant NCA (See VI.App.3.4), and for access to MAHs to fulfil their pharmacovigilance activities. Go back to step 1 on the receipt of a new information for the ICSR. NCA/MAH
13 No information is obtained for non-valid ICSR. No further information is obtained from the reporter for the non-valid ICSR. Go to step 13.1 NCA/MAH
13.1 Record outcome of the follow-up. Record the fact that no further information has been obtained from the reporter for the non-valid ICSR.
Go to step 13.2.		 NCA/MAH
13.2 END. End of the process for this non-valid ICSR. It should be considered as applicable in the safety evaluation activities. Go back to step 1 on the receipt of a new information. NCA/MAH
14 ICSR is not valid. The ICSR remains non-valid despite the new followup information received from the reporter. Go to step 14.1. NCA/MAH
14.1 End. End of the process for this non-valid ICSR. It should be considered as applicable in the safety evaluation activities. Go back to step 1 on the receipt of a new information. NCA/MAH