1. U.S. FDA Approach to Auditing Including QSIT
Christine Nelson
Center for Devices & Radiological Health
Food & Drug Administration
25 Sept. 2003
Frankfurt, Germany

2. FDA-Speak Terms Inspection = Audit Investigator = Auditor
25 Sept. 2003
Frankfurt, Germany

3. 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
When FDA inspects a medical device manufacturer, we evaluate the manufacturer’s compliance with FDA’s Quality System Regulation.
We also evaluate compliance with:
Registration and Listing regulation
The Medical Device Reporting regulation
Reports of Corrections and Removals regulation
Tracking Regulation for high risk devices
We inspect manufacturers of finished medical devices.
A finished medical device is one that is usable or capable of functioning. It does not have to be packaged or sterilized.
We also inspect contract manufacturers and contract sterilization facilities and others/
We do not inspect manufacturers of components, unless they are part of the finished medical device manufacturer.
25 Sept. 2003
Frankfurt, Germany

4. Who conducts inspections for FDA?
FDA investigators in 20 FDA District Offices around the U.S.
FDA-trained Auditors from Conformity Assessment Bodies in the European Union (EU)
In the future, FDA-trained auditors from independent third parties accredited by FDA
25 Sept. 2003
Frankfurt, Germany

5. 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
Device manufacturers are required to register with FDA and list the products they intend to distribute in the U.S.
FDA uses the registration database and the listing database to identify manufacturers for inspection.
FDA does not routinely inspect manufacturers of Class I devices.
We do prioritize our inspections by risk. We give a higher priority to inspecting manufacturers that make higher risk devices or are in high risk situations.
25 Sept. 2003
Frankfurt, Germany

6. 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
25 Sept. 2003
Frankfurt, Germany

7. Does FDA notify the manufacturer of an upcoming inspection?
FDA calls domestic manufacturers about 5 days before the inspection
FDA contacts foreign manufacturers months in advance to schedule inspection
Manufacturer is requested to send Quality System Manual or equivalent for pre- inspection review
25 Sept. 2003
Frankfurt, Germany

8. 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.)
25 Sept. 2003
Frankfurt, Germany

9. 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
25 Sept. 2003
Frankfurt, Germany

10. 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)
25 Sept. 2003
Frankfurt, Germany

11. What is QSIT? www.fda.gov/ora/inspect_ref/igs/qsit/qsitguide.htm
The Quality System Inspection Technique, or QSIT, is a plan for investigators to follow when evaluating a manufacturer’s compliance with regulations for Quality Systems, Medical Device Reporting, Corrections and Removals, and Tracking
Here is the internet site where you can obtain a copy of QSIT.
25 Sept. 2003
Frankfurt, Germany

12. 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
25 Sept. 2003
Frankfurt, Germany

13. What are the four main subsystems?
Corrective &
Preventive
Actions
Design
Controls
Production &
Process Controls
Management
FDA has identified 7 subsystems in the Quality System.
You can think of these subsystems as types of activities.
You want find these subsystems identified quite as clearly in the Quality System Regulation.
The four subsystems our investigators focus on are:
Management
Design control
Corrective and Preventive Actions and
Production and Process Control
When we inspect the Corrective and Preventive Action Subsystem, we will also evaluate compliance with the regulations for Medical Device Reporting, Reports of Corrections and Removals, and Tracking.
The QSIT handbook also includes guidance for covering sterilization when the Production and Process Control subsystem is inspected.
Equipment &
Facility Controls
Material Controls
Records, Documents, &
Change Controls
25 Sept. 2003
Frankfurt, Germany

14. What does FDA look for in the Management Subsystem?
Quality Policy established?
Management representative appointed?
Management reviews conducted?
25 Sept. 2003
Frankfurt, Germany

15. What does FDA look for in the Management Subsystem?
Quality audit procedures established and quality audits conducted?
Quality plan established?
Quality system procedures established?
25 Sept. 2003
Frankfurt, Germany

16. 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?
25 Sept. 2003
Frankfurt, Germany

17. 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?
25 Sept. 2003
Frankfurt, Germany

18. 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?
25 Sept. 2003
Frankfurt, Germany

19. 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?
25 Sept. 2003
Frankfurt, Germany

20. Processes are controlled and monitored?
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?
25 Sept. 2003
Frankfurt, Germany

21. Manufacturing processes validated or fully verified?
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?
25 Sept. 2003
Frankfurt, Germany

22. 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
25 Sept. 2003
Frankfurt, Germany

23. 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
25 Sept. 2003
Frankfurt, Germany

24. 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
25 Sept. 2003
Frankfurt, Germany

25. 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.
25 Sept. 2003
Frankfurt, Germany

26. Center for Devices & Radiological Health
25 Sept. 2003
Frankfurt, Germany

27. 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
25 Sept. 2003
Frankfurt, Germany

28. 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”
25 Sept. 2003
Frankfurt, Germany

29. 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
25 Sept. 2003
Frankfurt, Germany

30. What actions can FDA take to address OAI inspections?
For device manufacturers outside the U.S.:
Warning Letter
Warning Letter + Automatic Detention
25 Sept. 2003
Frankfurt, Germany

31. Warning Letter
FDA sends “Warning Letter” describing manufacturer’s violations of FDA regulations and requesting a reply within 15 days
25 Sept. 2003
Frankfurt, Germany

32. 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.
25 Sept. 2003
Frankfurt, Germany

33. 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.
25 Sept. 2003
Frankfurt, Germany

34. 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
25 Sept. 2003
Frankfurt, Germany

35. Where can I get more information about FDA inspections and regulations?
QSIT:
TGUIDE.PDF
guide.htm
Inspections of Medical Device Manufacturers Compliance Program : ces More . . .
25 Sept. 2003
Frankfurt, Germany

36. Where can I get more information about FDA inspections and regulations?
Quality system regulation: docs/cfcfr/CFRSearch.cfm?CFRPart=820
General quality system info:
Investigations Operations Manual: .htm More . . .
25 Sept. 2003
Frankfurt, Germany

37. Where can I get more information about FDA inspections and regulations?
Other medical device regulations:
Division of Small Manufacturers, International and Consumer Assistance -
Christine Nelson –
25 Sept. 2003
Frankfurt, Germany

38. 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
25 Sept. 2003
Frankfurt, Germany