The document outlines updates to Module IX of the GVP including shorter timelines for informing health authorities of emerging safety issues, submitting updates to product information or risk management plans within 3 months of signal validation, and reviewing EudraVigilance data more frequently. It indicates major potential impacts including setting up processes to meet new timelines and requirements as well as training personnel and managing resources accordingly.

1. GVP Module IX Rev. 1 and Addendum
1 (draft) – What to expect
Himanshu Bhatnagar

2. Disclaimer
• The guidelines are still in draft phase.
• With an expected release date in Q4 2017, there
might be some changes to the final form of the
Module, however, major revisions are not
expected going forward.

3. Important Sections Updated
• IX.B.2. to 4. – Signal detection
• IX.C.2. – Analysis of EudraVigilance data
• IX.C.3. – Procedure for validated signals

4. IX.C.2 – EudraVigilance data
monitoring
• MAH have to review the EudraVigilance database
periodically.
▫ Routine recommendation is monthly monitoring of the
database, but not less than 2/year (for established
products)
▫ For products under additional monitoring, it can be as
frequent as once in two weeks.*
• Potential Impact – Major
▫ Database review process to be set up
▫ Planning and pilot phase
▫ Personnel training
▫ Enhanced resource management
*Unless the additional monitoring is a PASS

5. IX.C.3 – Procedure for validated signals
• IX.C.3.1 – Emerging safety issues (ESI)
▫ Updated definition for ESI – “A safety issue…[with a]…
potential major impact on the risk-benefit balances of the
product and/or on patient or public health, that could
warrant prompt regulatory action and communication to
patients and healthcare professionals.”
• In case of an ESI, Health Authorities are to be informed
within two days of validation
• Potential Impact – Major
▫ Process update to ensure timely information delivery to HA
for ESI
▫ Process update to incorporate the shortened timelines
▫ Information dissemination to concerned functions

6. IX.C.3 – Procedure for validated signals
• IX.C.3.2 – If a change in Product Information or
RMP is mandated, it has to be submitted within
3 months. (NOTE – Day Zero is the date of
signal validation, not the date of decision on
signal after assessment)
• Potential Impact – Major
▫ Process update
▫ Information dissemination
▫ Enhanced resource management

7. IX.C.3 – Procedure for validated signals
• IX.C.3.3 – If a PSUR/PBRER Data Lock Point is
within 3 months of signal validation and it
doesn’t meet the criteria for ESI, it can be
included therein
• IX.C.3.4 – If a validated signal does not meet
any of the above criteria, the MAH is required to
submit a completed signal validation form
within 30 days of validation

8. IX.B.2 – Signal Detection
• Greater detail on sources for signals
• Statistical guidance for signal detection provided
in Addendum 1
• Potential Impact - Minor
▫ SOP updates
▫ Information dissemination to concerned functions

9. IX.B.3 – Evaluation of evidence
supporting a signal
• Greater detail on the elements to consider while
evaluating the evidence for a signal
▫ Strength of a signal (eg. Number of cases, patterns in
event occurrence, consistency, plausibility etc)
▫ Clinical relevance (eg. Severity, patterns in special
population groups)
▫ Previous awareness (presence on label, class action
etc)
▫ Additional sources (clinical data, literature, healthcare
databases)
• Potential Impact – Minor
▫ SOP updates
▫ Information dissemination to concerned functions

10. IX.B.4 – Signal Prioritization
• Elements to consider
▫ Severity, seriousness, and outcome
▫ Patient exposure, special populations, frequency
▫ Consequences of therapy discontinuation
▫ Anticipated extent of regulatory intervention
• Potential Impact – Minor
▫ SOP updates
▫ Information dissemination and training for
concerned functions

11. Summation
• Shortened timelines need an agile safety team
able to hit the ground running
• Signal validation process becomes more crucial
• Eudravigilance data review will necessitate
enhanced resource management
• Speed and Accuracy are of the utmost
importance – no time or scope for error!