Transcript The FDA’s Postmarketing Adverse Drug Experience Inspectional Program

The FDA’s Postmarketing
Adverse Drug Experience
Inspectional Program
Surveillance Programs Team
Office of Compliance
Center for Drug Evaluation and
Research
U.S. Food and Drug Administration
1
AGENDA

Postmarketing adverse drug experience
reporting regulations

Role of headquarters and field

Inspectional strategies
2
Purpose of ADE Regulations

To obtain additional information on
adverse events that may not have been
detected prior to marketing

To improve the labeling of drug products
3
Brief Overview of Reporting
Regulations

21 CFR Sections:
• 310.305 - RX drugs not subject to
approved applications
•
314.80 - RX drugs subject to
NDAs/ANDAs and OTCs associated with
approved applications
• 314.98- RX drugs subject to AADAs
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What is an Adverse Drug
Experience?

Any adverse event associated with the
use of drug in humans whether or not it
is considered drug related.
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Serious Adverse Drug Experience
Death
 Life threatening (per initial reporter)
 Permanently or significantly disabling
 Hospitalization
 Congenital anomaly/birth defect
 Important medical events

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Unexpected Adverse Drug
Experience

Not listed in current labeling

Listed in labeling but greater specificity
or severity
• e.g. renal impairment listed, patient
experiences renal failure
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Reporting Requirements

Within 15 calendar days if Serious and
Unexpected (domestic and foreign)

Follow-up information

Non-applicant notifies applicant within
five calendar days
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Periodic Report

Quarterly and Annual Reports
• Serious & Expected ADEs
• All Non-serious
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When does the Regulatory
Clock Start?

First day a firm or any affiliate receives
event data containing all four elements:
• An identifiable patient
• An identifiable reporter
• A suspect drug
• An adverse event or fatal outcome
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Forms

3500A (Medwatch Form)

Council for International Organization of
Medical Science (CIOMS I Foreign) or
other form if approved in advance
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The Headquarter/Field
Adverse Event Team
The headquarters scientists use
adverse event reports to evaluate the
safety of marketed drugs
 OC/ADE Team coordinates between
regulatory and scientific staff.
 The field investigators assure industry
compliance with reporting regulations

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Role of the Field Investigator

To verify through on-site visits that firms
are submitting all required reports of
adverse events to FDA and the reports
are complete, accurate and timely.
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Role of the Field Investigator

When reports of adverse events are not
submitted, or are incomplete, inaccurate
or late, then document to support
appropriate regulatory action.
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Role of the Field Investigator

Look for adverse events not cited on the
product labeling.

Do not make medical evaluation of
adverse events.

Do not evaluate labeling or make
labeling change recommendations
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Selection of the Firms
Risk Management Approach

Firms with ADE reporting problems

Firms with prior violative history

Recalls

AIP list

NDA field alerts

High-risk drugs
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References Used Prior,
During and After Inspection

CP 7353.001, Enforcement of the
Postmarketing Adverse Drug
Experience Reporting Regulations.

Regulations

Guidance documents

Inspectional package
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SOPs
Procedure to specify the minimum
qualifications of persons involved in
investigating and evaluating ADEs
 Make sure that current reporting
requirements are cited in SOPs
 SOPs should specify control activities to
ensure that ADEs are investigated,
followed-up, evaluated and sent to FDA.

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Source Documents

Complaint logs - numerical for
completeness

Medical Department Logs

Distribution records

Annual product reviews
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We are looking for...

Outcomes to identify problem areas for
inspectional coverage.

What system failure(s) caused the firm
not to comply with the regulations.
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Look for Discrepancies such as...

Omissions

Minimizing results

Lack of follow-up

Inadequate follow-up
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Significance of Deviations

Most serious - not submitting 15-day
reports

Serious - report accuracy

Moderately serious - timeliness
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If reports are found
that have not been filed...

Determine the nature of the event and
the cause for failure to report.

Determine what changes have been
made to prevent reoccurrence.
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When Discrepancies are Found

Review raw data

Ask questions and understand how the
event and investigation was handled

Look for patterns or trends

Document
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Type of Violations Uncovered

Serious and unlabeled events not
submitted in a timely manner (range 30
days up to ten years

Lack of assurance that all ADEs were
submitted

Foreign serious and unlabeled events
not submitted from foreign affiliates
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Cont. Violations Uncovered

Failure to conduct prompt and adequate
follow-up investigations of ADEs

Serious and unlabeled events not
assessed properly

No periodic reports submitted
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Cont. Violations Uncovered

Computer system used to process and
generate ADR reports is not validated

Coding errors in Medwatch forms

No approved SOPs
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Remember
Scientific evaluation of adverse events
depends upon the field investigator
assuring that industry submits reports
that are complete, accurate, and timely.
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For Additional Information...Contact
the Surveillance Program Team
Jay Schmid – 301-827-8929
[email protected]
•
Carol Krueger – 301-827-8989
[email protected]
•
Juliaette Johnson – 301-827-8928
[email protected]
•
Denis Mackey – 301-827-8926
[email protected]
•
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Internet Sites for ADR
Information

http://www.fda.gov/cder/aers/index.htm

http://www.fda.gov/cder/regguide.htm

http://www.fda.gov/medwatch
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