by: Nashmia Zia

Understand Pharmacovigilance
Define Postmarketing Surveillance
Describe the role of Center for Drug Evaluation and
Research (CDER) in FDAs Postmarketing Surveillance
programme.
Understand components of postmarketing drug
safety surveillance.
Understand the FDA Adverse Event Reporting
System (FAERS) and describe how adverse event
reports are collected and analyzed by
FDA/CDER/DPV
Understand regulatory requirements and the role of
MedWatch for reporting postmarketing safety
information.
by: Nashmia Zia

The science and activities relating to the

identification, recording, reporting and analysis of
safety information so that any safety signals that
arise at any stage of life cycle of drug are quickly
identified and acted upon.

by: Nashmia Zia

 Reported information on a
possible causal relationship
between an adverse event and a
drug
The relationship being
previously unknown or
incompletely documented
Usually requires more than a
single case report to generate a
signal

by: Nashmia Zia

New unlabeled adverse

events
An observed increase in
a labeled event OR a
greater severity or
specificity
New interactions

Newly identified
atrisk population

Preclinical
Safety
&
Biological
Activity

Phase 1 Phase 2 Phase 3

Safety
&
Dosage

Safety
&
Efficacy

Safety
&
Efficacy

A
P
P
R
O
V
A
L

PostMarketing
Safety
Surveillance

Safety Concerns

Strategies and Actions to Minimize Risk

by: Nashmia Zia

by: Nashmia Zia

Center for
Food
Safety &
Applied
Nutrition
(CFSAN)

Center for
Veterinary
Medicine
(CVM)

Center for
Devices &
Radiological
Health (CDRH)

by: Nashmia Zia

Center for
Biologics
Evaluation
& Research
(CBER)

Center for
Drug
Evaluation
& Research
(CDER)

Center for
Tobacco
Products (CTP)

Office of
Regulatory
Affairs (ORA)

Center for
Drug
Evaluation
& Research
(CDER)

Office of
Surveillance &
Epidemiology

CDER evaluates
the safety
profiles of drugs
available to
American
consumers
throughout the
life cycle of the
drugs

use this
information to

by: Nashmia Zia

CDERs data of
premarket
safety
evaluation.

CDER's data from

active
postmarketing
surveillance and
risk assessment
programs

1. identify drug safety

concerns
2. recommend actions
to improve product
safety

by: Nashmia Zia

Postmarketing surveillance (PMS) (also post

market surveillance) is the practice of
monitoring the safety of a pharmaceutical
drug or medical device after it has been
released on the market.

by: Nashmia Zia

 Size of the patient population studied

Narrow population often not providing sufficient data on
special groups
Narrow indications studied
Short duration

by: Nashmia Zia

The ability to study the following:

Low frequency reactions (not identified in clinical trials)

High risk groups
Longterm effects
Drugdrug/food interactions
Increased severity and / or reporting frequency of known
reactions

by: Nashmia Zia

1. reporting of cases (Mandatory/voluntary)

2. Post-marketing studies (voluntary or required)

National (FDA MedWatch)

Scientific literature publications
Observational studies (including automated healthcare
databases)
Randomized clinical trials

3. Active surveillance

Sentinel initiative

by: Nashmia Zia

 Voluntary

Reporting for Consumers and

Healthcare Professionals
Mandatory Reporting for Regulated Industry
and User Facilities

Report a Serious Medical Product Problem

Online by MEDWATCH
Online Dietary Supplement Problem Reporting &
Online Tobacco & biologics Product Problem
Reporting by SAFETY REPORTING PORTAL (SRP)

by: Nashmia Zia

by: Nashmia Zia

Adverse Effects
Any incident in which a medical product was suspected to
have resulted in an undesirable experience for the patient.
Product Use Error
Any medication or medical product error regardless of
patient involvement and outcome. Also report
circumstances that have the capacity to cause error, such
as similar label appearance.
Product Problem
Any concerns about the quality, authenticity, performance,
or safety of any medication or device
Problem with Different Manufacturer of Same Medicine
Any differences in therapeutic response after switching
from one manufacturer to another

by: Nashmia Zia

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http://www.fda.gov/Safety/MedWatch/HowToReport/DownloadF
orms/default.htm link for downloadable forms

by: Nashmia Zia

 Online
(www.fda.gov/medwatch)
Download the form
Mail
Fax 18003320178

For questions about the form:

18003321088

by: Nashmia Zia

Online Dietary Supplement & biologics Problem Reporting & Online Tobacco Product
Problem Reporting
https://www.safetyreporting.hhs.gov/fpsr/WorkflowLoginIO.aspx?metinstance=F3364E
33E164EBA7A4FE95252FEC184FCC304D42 link

by: Nashmia Zia

Media attention
Litigation (class action lawsuits)
Nature of the adverse event
Type of drug product and indication
Length of time on market
Extent and quality of manufacturers surveillance
system
Rx or OTC product status
Reporting regulations

by: Nashmia Zia

by: Nashmia Zia

Patients, consumer, and healthcare professionals

Voluntary

Voluntary

Manufacturer

FDA MedWatch

Regulatory
Requirements

FDA
FAERS
Database

5% of all reports

95% of all reports

FAERS reports are analyzed by CDERS &

CBERS to identify

SAFETY SIGNAL

The FDA Adverse Event Reporting System (FAERS)

is a database that contains information on
adverse event and medication error reports
submitted to FDA

Contains human drug and therapeutic biologic

reports
> 7 million reports since 1969
The reports in FAERS are evaluated by clinical
reviewers in the Center for Drug Evaluation and
Research (CDER) and the Center for Biologics
Evaluation and Research (CBER) to monitor the
safety of products after they are approved by FDA

by: Nashmia Zia

FAERS Statistics: provides numbers of reports

that FDA has received for drug and therapeutic
biologic products over the past ten years.
FAERS Data Files: provides raw data consisting of
individual case safety reports extracted from the
FAERS database. A simple search of FAERS data
cannot be performed with these files by persons
who are not familiar with creation of relational
databases.
Individual case safety reports from the FAERS
database can also be obtained by sending
a Freedom of Information (FOI) request to FDA.

by: Nashmia Zia

Growing Number of Adverse Event Reports

1,000,000

900,000
800,000

PERIODIC (Non-Expedited)

15-DAY (Expedited)

Number of Reports

700,000

DIRECT

600,000

500,000

400,000

300,000

200,000

100,000

2001

2002

2003

2004

2005

2006

2007

Calendar Ye ar

by: Nashmia Zia

2008

2009

2010

2011

2012

 Includes all U.S.

marketed products
Includes broad
patient populations:

elderly, children,
pregnant women,
comorbidities

Simple, relatively
inexpensive reporting
system

by: Nashmia Zia

Useful for events that

occur shortly after
exposure
Detection of events not
seen in clinical trials
signal generation
Identification of trends,
possible risk factors,
populations, and other
clinically significant
emerging safety concerns

Worsening of preexisting disease

Issue is beyond the name of the drug
Disease is reflected in the adverse event
Looking for drug interactions
Reporting Biases

by: Nashmia Zia

Did you
see it??
signal

by: Nashmia Zia

by: Nashmia Zia

 Mathematical tool identifies higher

thanexpected frequency of
productevent combinations
Tool for hypothesis generation or
support for further work on a
hypothesis
Supplements FAERS data review
Does not replace expert clinical case
review

by: Nashmia Zia

by: Nashmia Zia

 Use FAERS, published literature, Datamining and other

sources to identify safety signal.
Use knowledge of the clinical course of the disease to
perform a thorough database search strategy based on
Medical Dictionary for Regulatory Activities (MedDRA)
coding

by: Nashmia Zia

 Labeling changes i.e. Warnings, Precautions, Adverse

Reactions
Pharmacovigilance activities enhanced surveillance
registry, epidemiology studies
Risk Evaluation and Mitigation Strategy (REMS)
Communication plan, restricted use

Market withdrawal

by: Nashmia Zia

by: Nashmia Zia

 MedWatch Safety Alerts

Drug Safety Newsletter
Postmarket Drug and Biologic Safety Evaluations (FDAAA
915)
Potential Signals of Serious Risks/New Safety Information
Identified from FAERS (FDAAA 921)
Published literature and scientific meetings
Video and teleconferences with foreign regulatory
agencies:
European Medicines Agency, Canada, Australia, New Zealand
by: Nashmia Zia

CASE REPORTS
(MEDWATCH + SRP)
Voluntary & mandatory

FAERS
Identification of safety signal

Data mining
Different data bases + Sentinel database

Labeling changes
Enhanced Pharmacovigilance activities

Market withdrawal
by: Nashmia Zia

by: Nashmia Zia

Arthur N et al. The Importance of Pharmacovigilance Safety Monitoring of Medicinal

Products. WHO 2002.
Drug Safety Communications: http://www.fda.gov/Drugs/DrugSafety/ucm199082.htm
FDA Patient Safety News: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/psn/index.cfm
Guidance for )ndustry Postmarketing Safety Reporting for Human Drug and Biological
Products including Vaccines, March 2001:
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Gui
dances/Va ccines/ucm074850.htm
Guidance for )ndustry Good Pharmacovigilance Practices and Pharmacoepiemiologic
Assessment, March 2005:
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126834.pdf
MedWatch: The FDA Safety Information and Adverse Event
Reporting Program:
http://www.fda.gov/Safety/MedWatch/default.htm
MedWatch Medical Product Safety Information:
http://www.fda.gov/Safety/MedWatch/SafetyInformation/
default.htm
MedWatch Safety Alerts: http://www.fda.gov/Safety/MedWatch/ucm287881.htm
MedWatch Safety Alert RSS Feed:
http://www.fda.gov/AboutFDA/ContactFDA/StayInformed/RSSFeeds/MedWat
ch/rss.xml
Postmarket Drug Safety Information for Patients and Providers (FDAAA 915):
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProv
iders/defa ult.htm
Postmarketing Drug and Biologic Safety Evaluations: (FDAAA 915):
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/ucm2
04091.htm
Potential Signals of Serious Risks/New Safety Information Identified from AERS (FDAAA 921):
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Surveillance/Advers
eDrugEffec ts/ucm082196.htm#QuarterlyReports
by: Nashmia Zia