U.S. FDA Approach to
Auditing Including QSIT
Christine Nelson
Center for Devices & Radiological Health
Food & Drug Administration
25 Sept. 2003
Frankfurt, Germany
1
FDA-Speak Terms
 Inspection = Audit
 Investigator = Auditor
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Frankfurt, Germany
2
Why does FDA inspect device
manufacturers?
 To evaluate compliance with the
following FDA device regulations:
 Quality Systems
 Medical Device Reporting
 Medical Device Tracking
 Reports of Corrections and
Removals
 Registration and Listing
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Frankfurt, Germany
3
Who conducts inspections for FDA?
1. FDA investigators in 20 FDA District
Offices around the U.S.
2. FDA-trained Auditors from Conformity
Assessment Bodies in the European
Union (EU)
3. In the future, FDA-trained auditors from
independent third parties accredited by
FDA
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Frankfurt, Germany
4
How does FDA decide who to
inspect?
 Registration database identifies who
manufactures devices for distribution in
the U.S.
 Listing database identifies what devices
they distribute
 FDA prioritizes inspections by risk and
gives higher risk devices/situations a
higher priority
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What is high priority for inspection?
 Device manufacturers that:
 Make
class III devices
 Make
implantable devices and life
supporting and life sustaining devices
 Recently
introduced a new device to the
market
 Have
had significant violations in the
past
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Does FDA notify the manufacturer
of an upcoming inspection?
 FDA calls domestic manufacturers about
5 days before the inspection
 FDA contacts foreign manufacturers 2 - 3
months in advance to schedule inspection
 Manufacturer is requested to send Quality
System Manual or equivalent for preinspection review
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What happens when the FDA
investigator arrives at the site?
 The FDA investigator will:
 Ask
to see the top management
 Present
credentials (identifies person
as an FDA investigator)
 Issue
notice of inspection explaining
FDA’s legal authority to inspect (only
in the U.S.)
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What happens during the
inspection?
 Investigator may tour the facility to get
an idea of layout, workflow, and areas
that may need closer inspection
 This helps the investigator
decide how to organize
the inspection
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What happens next?
 The investigator will:
 Ask
about size and structure of
company, who is in charge, what
products are manufactured there
 Review
registration and listing
 Evaluate
compliance with FDA
regulations using the Quality System
Inspection Technique (QSIT)
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Frankfurt, Germany
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What is QSIT?
www.fda.gov/ora/in
spect_ref/igs/qsit/q
sitguide.htm
FOOD AND DRUG
ADMINISTRATION
GUIDE TO INSPECTIONS OF
QUALITY SYSTEMS
August 1999
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What is QSIT?
 Identifies 4 major subsystems to
evaluate and states the purpose and
importance of each subsystem
 Provides flowcharts and inspectional
objectives to cover during inspection
 Offers advice
 Provides tables for statistical sampling
of records for review
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Frankfurt, Germany
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What are the four main subsystems?
Design
Controls
Corrective &
Preventive
Actions
Production &
Process Controls
Management
Material
Controls
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Records,
Documents, &
Change Controls
Frankfurt, Germany
Equipment &
Facility Controls
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What does FDA look for in the
Management Subsystem?
 Quality Policy established?
 Management representative
appointed?
 Management reviews conducted?
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What does FDA look for in the
Management Subsystem?
 Quality audit procedures
established and quality audits
conducted?
 Quality plan established?
 Quality system procedures
established?
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Frankfurt, Germany
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What does FDA look for in the
Design Control Subsystem?
 Design procedures and plan established?
 Design inputs or requirements for device
identified?
 Design outputs or specifications for
device identified?
 Design verification conducted?
 Design validation conducted?
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Frankfurt, Germany
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What does FDA look for in the
Design Control Subsystem?
 Software validation completed?
 Risk analysis carried out?
 Design reviews conducted?
 Design transfer to manufacturing
completed successfully?
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Frankfurt, Germany
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What does FDA look for in the Corrective
and Preventive Action Subsystem?
 CAPA procedures established?
 Sources of data analyzed to identify
nonconforming product and quality
problems?
 Statistical analysis across data
sources?
 Investigations conducted to identify root
cause of failures?
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Frankfurt, Germany
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What does FDA look for in the Corrective
and Preventive Action Subsystem?
 Nonconforming product controlled?
 Appropriate corrective actions and
preventive actions carried out?
 Those responsible are told about CAPA
activities?
 Management review of CAPA activities?
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What does FDA look for in the Production
and Process Control Subsystem?
 Processes are controlled and
monitored?
 Any rejects or nonconforming
product?
 Equipment adjusted, calibrated and
maintained?
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What does FDA look for in the Production
and Process Control Subsystem?
 Manufacturing processes validated
or fully verified?
 Software validated?
 Production employees trained and
qualified?
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What about the other subsystems?
 The other three subsystems are covered
through links with the four main
subsystems:
 Records,
 Facility
and equipment control
 Material
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documents and change control
control
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What happens at the end of the
inspection?
 The investigator will:
 Meet
with management to discuss the
inspection
 Present
the FDA 483 list of
observations of any
significant deficiencies
 Discuss
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the deficiencies
Frankfurt, Germany
23
What should the manufacturer do
after the inspection?
 Send a letter to FDA identifying how they
have corrected deficiencies or will correct
them
 Provide documentation of any corrections
that have been completed
 Provide a timetable or estimated
completion date for future corrections
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Where should I send the letter?
Office of Compliance
Center for Devices and Radiological
Health (CDRH)
Food and Drug Administration
2094 Gaither Road, HFZ-300
Rockville, Maryland 20850
U.S.A.
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Frankfurt, Germany
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Center for Devices & Radiological Health
Office of the
Center Director
Office of Device
Evaluation
Office of In Vitro Diagnostic
Device Evaluation & Safety
Office of
Compliance
Office of Surveillance
& Biometrics
Office of Science
& Technology
Office of Systems
& Management
Office of Health &
Industry Programs
Division of Small Manufacturers,
International & Consumer Assistance
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Office of Compliance
Division of Enforcement A
Division of Enforcement B
 Dental, ENT &
 Cardiovascular &
Ophthalmic Devices
 OB/GYN, Gastro &
Urology Devices
 General Hospital
Devices
 General Surgery
Devices
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Neurological Devices
 Diagnostic X-ray
Devices
 Electronic Products &
Devices
 Orthopedic, Physical
Medicine &
Anesthesiology Devices
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What happens next?
 Investigator writes an “Establishment Inspection
Report” or EIR
 EIR is sent to the Office of Compliance, Center
for Devices and Radiological Health (CDRH)
 Inspection is classified based on inspectional
findings
 Office of Compliance reviewer writes Warning
Letter for inspection classified “OAI”
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How does FDA classify inspection
reports?
 NAI – No action indicated
 VAI – Voluntary action indicated – some
deficiencies identified but not serious
 OAI – Official action indicated –
serious deficiencies identified,
and FDA must take action to
assure correction
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What actions can FDA take to
address OAI inspections?
 For device manufacturers
outside the U.S.:
 Warning
Letter
 Warning
Letter +
Automatic Detention
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Warning Letter
 FDA sends “Warning Letter”
describing manufacturer’s violations
of FDA regulations and requesting a
reply within 15 days
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Warning Letter + Automatic Detention
 FDA sends “Warning Letter” describing
manufacturer’s violations of FDA
regulations and requesting a reply within
15 days
 Manufacturer’s products
are put on automatic
detention to prevent
them from entering the U.S.
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What will the Warning Letter say
about Automatic Detention?
 Given the serious nature of these violations of
the Act, all products manufactured at this
facility may be detained without physical
examination upon entry into the United
States. In order to prevent your devices from
being detained without physical exam, your
firm will need to respond to this Warning
Letter (as set forth below) and correct the
violations noted in this letter. In addition, the
agency usually needs to conduct a follow-up
inspection to verify that the appropriate
corrections have been implemented.
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How do I get my devices off
automatic detention?
 Submit documentation to FDA showing
that deficiencies have been corrected
 FDA will inspect you to confirm that
corrections are adequate before lifting
automatic detention
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Where can I get more information about
FDA inspections and regulations?
 QSIT:

http://www.fda.gov/ora/inspect_ref/igs/qsit/QSI
TGUIDE.PDF

http://www.fda.gov/ora/inspect_ref/igs/qsit/qsit
guide.htm
 Inspections of Medical Device Manufacturers
Compliance Program 7382.845:
http://www.fda.gov/ora/cpgm/default.htm#devi
ces
More . . .
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Where can I get more information about
FDA inspections and regulations?
 Quality system regulation:
http://www.accessdata.fda.gov/scripts/cdrh/cf
docs/cfcfr/CFRSearch.cfm?CFRPart=820
 General quality system info:
http://www.fda.gov/cdrh/devadvice/32.html
 Investigations Operations Manual:
http://www.fda.gov/ora/inspect_ref/iom/default
.htm
More . . .
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Frankfurt, Germany
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Where can I get more information about
FDA inspections and regulations?
 Other medical device regulations:
http://www.fda.gov/cdrh/devadvice/
 Division of Small Manufacturers, International
and Consumer Assistance - E-mail:
dsma@cdrh.fda.gov
 Christine Nelson – E-mail: mcn@cdrh.fda.gov
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Summary
 Quality System Inspection Technique (QSIT)
 How FDA conducts inspections
 What should a manufacturer do after an
inspection
 Warning Letter or Warning Letter + Automatic
Detention
 Where to go for more information
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