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Tuesday, 16 June 2020

Timelines for adverse drug reports in Pharmacovigilance


Have you wondered why PV professionals seem to be under stress regarding meeting timelines? Its friday evening and you have plans but then the last minute SUSAR comes in inbox and your friday is gone.We all have some or the other time faced this as PV professionals.

What are the timelines in PV and why they are so urgent and important?

We can divide this topic in 2 sections for ease of understanding.

1. ICSR timelines (Individual Case Safety Reports)/Adverse drug event reports.*
2. Aggregate report timelines
3. Others

In this blog i wanted to cover ICSR timelines and Aggregate report consisting of ICSRs, so as to keep the length of blog short and easy for comprehension.

Every Health Authority (HA) has there own timelines as per regulations, i will highlight four main HA timelines i.e. EU, US, India and Japan.

1.  Europe

a) Spontaneous ICSRs:

Submit the valid ICSR (EEA) (European Economic Area) and non-EEA serious (non life threatning and non -fatal) within 15 days from initial receipt of the information, and EEA non-serious ICSR within 90 days from initial receipt of the information to EudraVigilance (EV)).

 Non-serious non-EEA ICSRs should not be submitted to EV.

We should remember it says within 15 days, most of the HA mean it as soon as possible but within 15 days, this is important to understand and make sure to write it this way in internal SOPs. 
Also, serious (fatal and life threatening) ICSR the timeline is within 7 days for EEA and Non-EEA.

b) Clinical ICSRs:

SUSARs (suspected serious unexpected adverse reactions) that are fatal or life-threatening are submitted as soon as possible but within 07 days and relevant follow-up information within an additional 08 days from initial receipt of the information .
In addition to reporting to EU, this needs to be submitted to Ethics Committee and Investigators. 

All other suspected serious unexpected adverse reactions  (non life threatening and non -fatal) are submitted to the HAs concerned and to the Ethics Committee concerned as soon as possible but within 15 days from initial receipt of the information

2. United States

a) Spontaneous ICSRs:

ICSRs that are serious and unexpected, whether foreign or domestic, are to be submitted as soon as possible but within 15 calendar days from initial receipt of the information and must submit follow-up reports within 15 calendar days of receipt of new information to FDA.

The non-SUSAR cases timelines are covered in aggregate reporting timelines.

b) Clinical ICSRs

Submit unexpected fatal or life-threatening suspected adverse reaction (SUSARs) as soon as possible but within 7 calendar days from initial receipt of the information to FDA.

In addition to FDA, they are to be submitted to all participating investigators  in an IND safety report  as soon as possible, but within 15 calendar days from receipt of information and to Ethics committee as applicable.

3. INDIA

a) Spontaneous ICSRs:


All serious AEs/ADR (adverse events (AE) and adverse drug reactions (ADR)) must be reported to regulatory authority CDSCO/PvPI, IPC within 15 days from receipt of information .

All non-serious AEs/ADR must be reported to CDSCO/NCA-PvPI, IPC within 30 days from receipt of information.


b) Clinical ICSRs: All serious adverse events must be submitted to DCGI within 14 calendar days receipt of information.

In addition to DCGI, it needs to be submitted to ethics committee (local and national) and Investigators. 

One important thing to note here is, for India, it says licensing authority and regulatory authority. Licensing authority can be DCGI or state FDA and regulatory authority is CDSCO but submission to  PVPI is needed too. This is my understanding. There is email (xml file + DCGI format) and paper submission.

4. Japan

 ICSRs:

ICSRs that are serious and unexpected (unpredictable), are to be submitted as soon as possible but within 15  days from initial receipt of the information to PMDA.

ICSRs that are serious and expected (predictable) within 30 days. This excludes serious death expected ICSR which were caused by new drug  within 2 years of approval and ICSR from drug which is under EPPV program (Early phase post marketing vigilance) which are to be submitted within 15 days.

Non serious unexpected (unpredictable) ICSRs are submitted annually and non serious listed (predicatble) not submitted. 

EPPV-Early phase post marketing vigilance - This  is for newly approved drugs when 2 years have not passed from the date of approval for drugs


Aggregate reports:

1. US:

ICSRs that are serious listed, non-serious unlisted and listed are submitted at quarterly intervals, for 3 years from the date of approval of the application, and then at annual intervals.Each quarterly report is submitted within 30 days of the close of the quarter and each annual report within 60 days of the anniversary date of approval of the application. Follow-up information to adverse drug experiences submitted in a periodic report may be submitted in the next periodic report.

*for the sake of ease i have considered ICSR and Adverse drug reaction report and event as equivalent, however they are not and standard definitions can be found in HA guidance documents.


References:




 Written by:


Dr.shraddha Bhange.

Content co-developed by:

Dr.Sridhar Yeshamaina
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