Aggregate Reporting in Pharmacovigilance

Pharmacovigilance, the science of monitoring and evaluating the safety of medicines, relies on a robust system of data collection, analysis, and reporting. In this complex landscape, aggregate reporting emerges as a critical component, playing a pivotal role in safeguarding patient well-being and enhancing regulatory compliance.

What is Aggregate Reporting?

Aggregate reporting in pharmacovigilance involves the analysis and compilation of safety data from multiple sources to provide a comprehensive overview of a drug's safety profile. This process goes beyond individual case reports and seeks to identify broader trends and patterns related to adverse events. It allows regulatory authorities, pharmaceutical companies, and healthcare professionals to make informed decisions regarding drug safety.

1. Welcome
Aggregate Reporting in Pharmacovigilance
Dr.Sakthiyavathi K
B.D.S.
CSRPL_STD_IND_HYD_ONL/CLS_181/092023
10/01/2023
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Index
Introduction
Categories
Pre-approval Vs Post-approval
DSUR
PADER
PBRER
PADER Vs PBRER
Addendum of Clinical Overview
Reporting Timeline
Conclusion

3. Aggregate Reporting
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Comprehensive and cumulative safety profile of an investigational product
Systematically analyzed, summarised benefit/risk information
Throughout the product’s life cycle
Communicated to the appropriate regulatory health authorities in specified timelines
Appropriate action to enhance patient safety through effective risk minimization plans and
implementation needs to be taken, update the medicinal product’s label

4. Categories
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Pre-approval
Annual safety reports (ASR)
Europe
IND annual reports
U.S.
Development Safety Update
Report (DSUR)
ICH regions
Post-approval
PADER (Periodic Adverse Drug Experience
Report)
Periodic Benefit Risk Evaluation Report
(PBRER))/
Periodic safety update report (PSUR)
Addendum to Clinical Overviews (ACO)

5. Pre-approval Vs Post-approval
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*Cumulative summary of safety information
*Drug or molecules under clinical development/clinical Trial
*Non-clinical studies
*Safety data from the subjects participated in clinical trial
*Cumulative summary of safety information
*Drug or molecules from the marketing exposure
*Non-clinical & clinical studies
*Literature articles and spontaneous cases (ADR)

6. Developmental Safety Update Report
(ICH E2F, 2010)
What?
Report the evolving safety profile of investigational medicinal product
To the respective health authority and local regulatory bodies
Contains;
Significant safety findings, serious adverse reactions in line listings
Similar safety information from published literature
When?
Within 1 year after Developmental International Birth Date (IBD)
Annually, until the last visit of the last patient
Within 60 calendar days from the DSUR data lock point (DLP)
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7. What?
Post-marketing safety report
To the respective health authority and local regulatory bodies
Contains;
Assessment & summary of an approved drug product’s benefit risk
profile
serious and unlisted cases which include concise narratives and
summary analysis of 15-day ICSR reports
Regulatory actions taken during the reporting interval since last
PADER
When?
Quarterly for first three years after marketing authorisation
Annually, in market for more than 2 years
Periodic Adverse Drug Experience Report
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8. Periodic Benefit Risk Evaluation Report
(ICH E2C-R2, 2012)
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What?
Post-marketing safety report
Evaluating the benefits and risks of medicinal products in long
term use
Assessment of new safety information
Contains;
Summary of new safety information of approved drug product
Update on previous risk/safety information
Risk minimisation actions taken during the reporting interval
When?
6 months for first 2 years
And then annually

9. Individual case narratives for
cases with serious/unexpected
events
5 sections , relatively less
complex
Separate PADER is to be
submitted with each NDA
approval
DLP: Quarterly < 30 days
Annual < 60 days
PADER Detailed analysis on the benefit-
risk evaluation of the given
medicinal product
20 sections, more complex
One PBRER is for an IP with
different formulations, dosage
forms, or indications
DLP : Annual < 70 days
PBRER
PADER Vs PBRER
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10. What?
Aggregate safety report similar to PBRER
Safety information emphasised since last renewal/approval
When?
No later than 9 months before the marketing authorisation ceases (EMA)
Addendum to Clinical Overview
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11. Reporting Timeline
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USFDA*

PADER
* Quarterly,
3 years from DOA,
<30 DLP.
* Annually until
drug withdrawal,
<60 DLP

PBRER
* Annually, <70 DLP
EMA*

PSUR
* Half yearly,
2 years from DOA,
<70 DLP
* Annually,
next 2 years,
<90 DLP
* Thereafter once in
3 years (ad hoc)
<90 DLP
HAS*,Singapore

PBRER
* Half yearly,
2 years from DOA
* Annually,
next 3 years
* <70 DLP
until 12 months
* >90 DLP
after 12 months
USFDA- U.S. Food and Drug Administration; EMA-European Medicines Agency ; HAS-Health Sciences authority

12. Reporting Timeline
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TGA*, Australia

PSUR
* Annually for 3
years (or)
* Every 6 months
* <90 DLP
* After 3 years no
need to submit
PSUR unless
required
Health Canada

DCGI*, India

PSUR
*Half yearly,
2 years from DOA,
<30 DLP
*Annually,
next 2 years,
<30 DLP
*Thereafter as
required based on
the interest of
public health
TGA-Therapeutic Goods Administration; DCGI-Drugs Controller General of India
PBRER
* Annually, <70 DLP

PSUR
*Half yearly,
2 years from DOA,
<30 DLP
* Then annually

13. Conclusion
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Aggregate reporting is vital to help enhance the safety of the
investigational product throughout the drug life cycle, reported
periodically, thereby aiding to make necessary actions and risk
management plan for the safety of the product.

14. References
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1.Rathinavelsamy P. Overview of post marketing aggregate reports and global regulatory requirements. Int J Sci Rep. 2017
Dec;3(12):300-310
2.Kulkarni TN, Kulkarni NG. Authoring a periodic adverse drug experience report…here's what you need to know! Perspect Clin
Res. 2019 Apr-Jun;10(2):95-99. doi: 10.4103/picr.PICR_126_18. PMID: 31008077; PMCID: PMC6463498.
3.ICH Efficacy Guidelines, available at https://www.ich.org/page/efficacy-guidelines
4.Periodic Benefit-Risk Evaluation Report: ICH [Internet]. [cited 2019 Jun 26].
5.Guideline on the processing of renewals in the centralised procedure, Available from:
https://www.ema.europa.eu/en/documents/regulatory-procedural-guideline/guideline-processing-renewals-centralised-
procedure_en-0.pdf
6.Preparing and Submitting Summary Reports for Marketed Drugs and Natural Health Products - Guidance Document for Industry,
Available from: https://www.canada.ca/en/health-canada/services/drugs-health-products/reports-publications/medeffect-
canada/preparing-submitting-summary-reports-marketed-drugs-natural-health-products-guidance-industry.html

15. Thank You!
www.clinosol.com
(India | Canada)
9121151622/623/624
[email protected]

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