U.S. FDA Approach to Auditing Including QSIT

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U.S. FDA Approach to Auditing Including QSIT

• Christine Nelson
• Center for Devices Radiological Health
• Food Drug Administration

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FDA-Speak Terms

• Inspection Audit
• Investigator Auditor

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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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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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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 pre-inspection 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 FDAs 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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What is QSIT?

• www.fda.gov/ora/inspect_ref/igs/qsit/qsitguide.htm
  

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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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What are the four main subsystems?
Corrective Preventive Actions
Design Controls
Production Process Controls
Management
Equipment Facility Controls
MaterialControls
Records, Documents, Change 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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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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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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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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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, documents and change control
• Facility and equipment control
• Material 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 the deficiencies

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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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Center for Devices Radiological Health
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Office of Compliance

• Division of Enforcement A
• Dental, ENT Ophthalmic Devices
• OB/GYN, Gastro Urology Devices
• General Hospital Devices
• General Surgery Devices

• Division of Enforcement B
• Cardiovascular 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
  manufacturers violations of FDA regulations and
  requesting a reply within 15 days

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Warning Letter Automatic Detention

• FDA sends Warning Letter describing
  manufacturers violations of FDA regulations and
  requesting a reply within 15 days
• Manufacturers 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/QSITGU
  IDE.PDF
• http//www.fda.gov/ora/inspect_ref/igs/qsit/qsitgu
  ide.htm
• Inspections of Medical Device Manufacturers
  Compliance Program 7382.845 http//www.fda.gov/or
  a/cpgm/default.htmdevices More . . .

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Where can I get more information about FDA
inspections and regulations?

• Quality system regulation http//www.accessdata.f
  da.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFR
  Part820
• General quality system info http//www.fda.gov/cd
  rh/devadvice/32.html
• Investigations Operations Manual
  http//www.fda.gov/ora/inspect_ref/iom/default.htm
  More . . .

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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_at_cdrh.fda.gov
• Christine Nelson E-mail mcn_at_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