Pharmacovigilance sytem in United States of America (USA)

Pharmacovigilance System
in United States
Guidance Document

© PharmXL, 2020 All Rights Reserved
2 What is Pharmacovigilance?
3 CDER Organogram
4 Lifecycle of Products
5 Pharmacovigilance regulations in United States
6 Safety Signals
7 Risk Evaluation & Mitigation Strategy (REMS)
1 About PharmXL

3
WHO ARE WE
Regulatory Affairs
India Entry Services
360 degree
Pharma
solutions
NDA, ANDA, IND, MAA,
Dossiers, DMFs, SPCs,
PILs, Data review, Gap
analysis, Due diligence Protocol
development, site
selection strategies,
CRFs, ICDs, Data
Management,
Monitoring,
Biostatistics
Dedicated
Consultants
Deep stick study, Market
research, Partner search,
Distributor Search,
Company incorporation
SAE Narratives,
Annual safety report
writing, CCSI, CCDS,
SmPC, RSIs,
Brochures,
Feasibility reports
ICSRs, Reporting,
QPPV/PvOI, PSMFs,
PSURs, PBRERs,
Signal Detection,
Literature Search
is an emerging life sciences consulting company,
serving Globally.
 We provide support to our clients from pharmaceutical and Healthcare
field, with our complete range of regulatory services for Drug and
Medical Devices.
 We offer CRO services like Clinical research and trials; Regulatory
support in obtaining registration, approval, import license etc;
Pharmacovigilance services and Post-Marketing surveillance and
medical writing services to our clients.
 Our ambitious and dynamic leadership team is comprised of
enthusiastic, focused and experienced directorial. Working together
closely with our employees, their knowledge and expertise come
together to make a difference for all our clients –healthcare providers,
Pharmaceutical companies and communities around the globe.

4
What is Pharmacovigilance ?
WHO describes Pharmacovigilance as
“The science and activities relating to the detection, assessment, understanding, and prevention
of adverse effects or any other drug-related problems.”
• Drug safety is one of the foremost aspects, which is assessed during clinical trials and further
monitored throughout the drug’s lifecycle.
• Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research (CDER) under Food
and Drug Administration (FDA) are responsible authority for Pharmacovigilance activities in United
States.
• Further, it is described in organogram in following slide.

5
CDER Organogram
Office of
Compliance
Office of
Translational
Sciences
Office of
Surveillance &
Epidemiology
Office of
New Drugs
Office of
Generic
Drugs
Office of
Pharmaceutical
Quality
Office of
Pharmacovigilance
& Epidemiology
Office of Medication
Error Prevention &
Risk Management

6
Lifecycle of Products
Safety and
Biological
activity
Safety and
Dosage
Safety and
Efficacy
Safety and
Efficacy
Approval
and
Marketing Safety
Surveillance
Risk Minimization Plan
Pre-Clinical Phase 1 Phase 2 Phase 3
Phase 4:
Postmarketing
Safety Concerns

8
Pharmacovigilance regulations in United States
• FDA released two different guidance document for industry for Pharmacovigilance activities.
• In March 2005, FDA released a guidance document for Good Pharmacovigilance Practices and
Pharmacoepidemiologic Assessment.
• In April 2005, FDA released guidance document E2E Pharmacovigilance planning.
• As per 21 CFR, part 314 subpart B and subsection 314.80 discusses the postmarketing
reporting of adverse drug experience.

9
Postmarketing Safety Reporting Requirements
• FDA describes Adverse Drug Experience as any adverse event associated with the use of a drug in humans, whether
or not considered drug related, including the following:
• An adverse event occurring in the course of the use of a drug product in professional practice;
• an adverse event occurring from drug overdose whether accidental or intentional;
• an adverse event occurring from drug abuse;
• an adverse event occurring from drug withdrawal; and any failure of expected pharmacological action.
• Under 21 CFR 314.80 Postmarketing safety reports, two types of report must be submitted to the agency :
• 15-day Alert reports:
• Serious and unexpected adverse experience from all sources (domestic and foreign)
• Periodic Adverse Experience Reports:
• Serious and expected
• Non-serious and unexpected
• Non-serious and expected
• Quarterly for the first 3 years then annually
• Under 21 CFR 314.80, FDA may withdraw the approval if MAH found non-compliant to this establishment.

10
Serious Adverse Experience
• An Adverse Drug Experience, which results in any of these outcomes are considered Serious:
• Other Medically significant events are adjudged based upon appropriate medical judgment, they may
jeopardize the patient and require intervention to prevent a serious outcome.
Death
Life-
threatening
Hospitalization
Significant
Disability
Congenital
Birth Defect
Other
Medically
Significant
Events

11
15-Day Alert Reports
• The MAH must report each adverse drug experience that is both serious and unexpected.
• Both foreign and domestic cases must be reported, as soon as possible but no later than 15 calendar days from
initial receipt of the information by the MAH.
• FDA expects MAH to actively follow-up and investigate the alert reports and report the same. If additional
information is not obtainable, records should be maintained of the unsuccessful attempts to obtain additional
information.
• MAH must look for medical journals and scientific literatures publishing any ADE case reports from formal clinical
trials. A 15-day Alert report based on information in the scientific literature must be accompanied by a copy of the
published article.
• MAH is not required submit 15 Day alert reports from postmarketing studies, unless the MAH concludes that there
is a reasonable possibility that the drug caused the adverse experience.

12
15-Day Alert Reports
• FDA states characteristics of Good Case Reports as following:
• Description of the adverse events or disease experience, including time to onset of signs or symptoms;
• Suspected and concomitant product therapy details with NDC, Lot no. and other relevant details
• Patient characteristics, including demographic information (e.g., age, race, sex), and all other details
• Documentation of the diagnosis of the events, including methods used to make the diagnosis;
• Clinical course of the event and patient outcomes (e.g., hospitalization or death);
• Relevant therapeutic measures and laboratory data at baseline, during therapy
• Information about response to dechallenge and rechallenge; and
• Any other relevant information (e.g., other details relating to the event or information on benefits received
by the patient, if important to the assessment of the event).

13
Periodic adverse drug experience reports (PADER)
• The MAH is obliged to report periodic report at quarterly intervals for first 3 years and then annually.
• Quarterly reports should be submitted within 30 days of end of quarter and annual reports should be submitted
within in 60 days of end day of annual period.
• The MAH must report each adverse drug experience that is not reportable as 15-day alert reports i.e non-serious
cases and serious expected cases and it also includes analysis of 15-day alert reports barring foreign cases.
• FDA states contents of PADER:
Contents Description
Descriptive Information •A narrative summary and analysis of the information
•An analysis of the 15-day Alert reports barring Foreign case
•A history of actions taken since the last report because of
adverse drug experiences
•An index consisting of a line listing
ICSRs •All Serious expected and Non-serious Adverse Drug Experiences
barring foreign cases

14
Electronic Reporting of ICSRs
• Per 21 CFR 314.80, MAH are required to submit the reports in electronic format.
• Obliged Safety report submissions, including ICSRs, ICSR attachments, and the descriptive information in periodic
reports, must be in an electronic format that FDA can process, review, and archive.
• FDA will issue guidance on how to provide the electronic submission (e.g., method of transmission, media, file
formats, preparation and organization of files).
• The FDA Adverse Event Reporting System (FAERS) is a database that contains information on adverse event and
medication error reports submitted to FDA. The FAERS database adheres to the international safety reporting
guidance ICH E2B. Adverse events and medication errors are coded to terms in the Medical Dictionary for
Regulatory Activities (MedDRA) terminology.
• FDA uses FAERS data to monitor, identify and analyze adverse event and medication errors and regularly examine
the FAERS database as part of routine safety monitoring. When a safety signal is identified from FAERS data, it is
further evaluated
Medication
errors
Adverse Events
Product
problem

15
Database
Flow of ICSRs
Manual reporting
Patients, Consumers and healthcare professionals
Manufacturer
Voluntary
reporting
E2B reporting

16
Submission Methods
• There are two options for submitting ICSRs electronically
Safety Reporting Portal (SRP) Database-to-Database transmission (E2B)
Data is manually entered in web form
Do not have database-to-database capability
Must have an account to access the portal site
Gateway partners cannot use the SRP
Attachments must be in the PDF format
Use standardized ICH E2B(M) data elements
ICSRs must be submitted in the XML format
Attachments must be in the PDF format

17
FDA MedWatch
• MedWatch is the US-FDA’s “Safety Information and Adverse Event Reporting Program.” It interacts with the
FDA Adverse Event Reporting System (FAERS or AERS).
• MedWatch is used for reporting an adverse event or sentinel event. Founded in 1993, this system of voluntary
reporting allows such information to be shared with the medical community or the general public
• There are three types of MedWatch forms: MedWatch Form 3500 , MedWatch Form 3500A and MedWatch
Form 3500B
Form 3500 Form 3500A Form 3500B
For voluntary reporting
For use by HCP,
consumers, and patients.
 For Mandatory reporting
 For use by IND reporters,
manufacturers, distributors,
importers, user facilities
personnel.
For voluntary reporting for
consumers
A consumer-friendly version
of the 3500 reporting form.

18
FDA MedWatch
Form 3500 Form 3500A Form 3500B

20
Safety Signal
• What is Safety Signal?
• Safety signal refers to a concern about an excess of adverse events compared to what would be expected to be associated
with a product's use. Reported information on a possible causal relationship between an adverse event and a drug.
– Newly identified at-risk population.
– New unlabeled adverse events
– An observed increase in a labeled event OR a greater severity or specificity
– New interactions
– Usually supported by multiple case reports
• Sources of Safety Signal:
 Routine Pharmacovigilance
 FAERS, Data Mining and Periodic Safety Update Reports
 Study Results
 Medical Literature
 Media
 NDA Safety database
 Foreign regulatory agencies
 Others
• Based on potential of signal FDA may ask MAH to take certain action (Discussed in following slide).

21
FDA Actions: Warnings, Precautions & Adverse Reactions
Pharmacovigilance
-
Enhanced
Surveillance
Risk Evaluation
& Mitigation
Strategy
Drug Safety
Communication
Product
Information
Changes
Market
Withdrawal
Regulatory
Actions

23
Risk Evaluation Mitigation Strategies (REMS)
• A required risk management plan that uses risk minimization strategies beyond professional labeling to
ensure that the benefits of the drug outweigh the risks
• Each REMS has specific safety measures unique to the safety risks associated with a particular drug or class
of drugs
• MAH develop REMS programs; FDA reviews and approves them.
• The draft guidance documents were published on May 5, 2004, and the public was provided with an
opportunity to comment on them until July 6, 2004. FDA considered all of the comments received in
producing the final guidance documents.
1. Premarketing Risk Assessment (Premarketing Guidance)
2. Development and Use of Risk Minimization Action Plans (RiskMAP Guidance)
3. Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment (Pharmacovigilance Guidance)

24
Risk Evaluation Mitigation Strategies (REMS)
• Specifically, risk management is an iterative process of :
– Assessing a product’s benefit-risk balance
– Developing and implementing tools to minimize its risks while preserving its benefits
– Evaluating tool effectiveness and reassessing the benefit-risk balance
– Making adjustments, as appropriate, to the risk minimization tools to further improve the benefit-risk balance.
Medication Guide
or Package Insert
Elements to assure
safe use (ETASU)
Communication
plan for HCP
REMS
Implementation
Phase
REMS Requirement

THANKYOU
PharmXL International Pvt. Ltd.
B-3, Sector-6 Noida, Gautam Budh Nagar,
Uttar Pradesh -201301,
India
📧: contact@pharmxl.com
info@pharmxl.com
☏: +91-120-4563024;
+91-9266665231,
+91-9266665201
www.pharmxl.com

Pharmacovigilance sytem in United States of America (USA)

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Pharmacovigilance sytem in United States of America (USA)

Similar to Pharmacovigilance sytem in United States of America (USA) (20)

Recently uploaded

Recently uploaded (20)

Pharmacovigilance sytem in United States of America (USA)