1. The Quality System Inspection Technique (QSIT)
Paul R. Whitby
CONSUMER
SAFETY OFFICER
FDA/ORA/LOS-DO

2. REGULATIONS code of federal regulations
Food and Drugs 21
PARTS 800 to 1299
Revised as of April 1, 1998
Please do not confuse QSIT with the
Quality System Regulation
Quality System Regulation 21 CFR Part 820

3. QSIT is an Inspection Technique
QSIT Guide
Purpose and Importance
Objectives
Flow charts
Narratives
Sampling Plans
QSIT is not the QS Regulation
Preannounce
QSIT step towards harmonization

4. The QSIT Approach What is important is:
QSIT focuses on evaluating whether the Quality System and subsystems have been implemented effectively.
QSIT acknowledges that nonconforming product and quality problems happen.
What is important is:
Did the manufacturer identify the nonconforming product or quality problem?
Did the manufacturer take effective corrective and preventive action?

5. QSIT QSIT is a Top down approach
Key quality system sub-systems are audited
QSIT provides directions for sampling of records
The binomial staged sampling plans outlined in the QSIT guide help to indicate what the extent of any deficiencies may be

6. MANAGEMENT QSIT is based an auditing seven systems
Reports of Corrections and Removals
Medical Device Tracking
Medical Device Reporting
Corrective
&
Preventive Actions
Facility
&
Equipment Controls
Design
Controls
MANAGEMENT
QSIT is based an auditing seven systems
The four major systems are MC, DC, CAPA and P&PC
Production
&
Process Controls
Material Controls
Records/
Documents/
Change Controls
Sterilization Process Controls

7. QSIT Focuses on Four Major Subsystems
Management Controls
Design Controls
Corrective & Preventive Action Controls
Production & Process Controls

8. The Three Other Subsystems
Facility & equipment controls
Product controls
Documents, records & change controls

9. Satellites
Sterilization Process Controls are inspected as a satellite system to the Production and Process Controls Subsystem
Medical Device Reporting, Reports of Corrections and Removals, and Medical Device Tracking are satellites of CAPA

10. Management Controls Production & Design Controls Process Controls
Corrective &
Preventive
Actions
Equipment &
Facility Controls
Material Controls
Records, Documents, &
Change Controls
Emphasis is on Management Controls
Start and end the inspection with MC
Controls

11. Management Controls - Purpose
Provide adequate resources for device design, manufacturing, quality assurance, distribution, installation and servicing
Assure proper function of quality system
Monitor quality system
Make necessary adjustments

12. Management Controls - Inspectional Objectives
1. Verify that a quality policy, management review and quality audit procedures, quality plan, and quality system procedures and instructions have been defined & documented.
2. Verify that a quality policy and objectives have been implemented.
Underlined words are directions of activities to the investigator
You can review the QSIT book and see what we are directed to verify

13. Management Controls - Inspectional Objectives
3. Review the firm’s established organizational structure to confirm that it includes provisions for responsibilities, authorities and necessary resources.
4. Confirm that a management representative has been appointed. Evaluate the purview of the management representative.

14. Management Controls - Inspectional Objectives
5. Verify that management reviews, including a review of the suitability and effectiveness of the quality system are being conducted.
6. Verify that quality audits, including re-audits of deficient matters, of the quality system are being conducted.

15. Design Controls-Purpose
Control the design process to assure that devices meet:
user needs
intended uses
specified requirements

16. Focusing the Inspection of Design Controls...
52 Objectives (Design Control Inspectional Strategy)
36 Objectives (Design Control Report and Guidance)
15 Objectives (QSIT)

17. Design Controls - Inspectional Objectives
1. Select a single design project.
2. For the design project selected, verify that design control procedures that address the requirements of Section of the regulation have been defined and documented.
Inspectional Objectives for review of DC

18. Design Controls - Inspectional Objectives
3. Review the design plan for the selected project to understand the layout of the design and development activities including assigned responsibilities and interfaces.
4. Confirm that design inputs were established.

19. Design Controls - Inspectional Objectives
5. Verify that the design outputs that are essential for the proper functioning of the device were identified.
6. Confirm that acceptance criteria were established prior to the performance of verification and validation activities.
sampling tables are used

20. Design Controls - Inspectional Objectives
7. Determine if design verification confirmed that design outputs met the design input requirements.
sampling tables are used
8. Confirm that design validation data show that the approved design met the predetermined user needs and intended uses.

21. Design Controls - Inspectional Objectives
9. Confirm that the completed design validation did not leave any unresolved discrepancies.
10. If the device contains software, confirm that the software was validated.
11. Confirm that risk analysis was performed.

22. Design Controls - Inspectional Objectives
12. Determine if design validation was accomplished using initial production devices or their equivalents.
13. Confirm that changes were controlled including validation or where appropriate verification.

23. Design Controls - Inspectional Objectives
14. Determine if design reviews were conducted.
15. Determine if the design was correctly transferred.
What the CSO is directed to do

24. Using QSIT-
Sample
Review
Confirm
Verify

25. Sampling for Confidence
Using Table 1 and reviewing a population of 35 randomly selected records of one type (DHR) and finding just one deviation.
The investigator can be 95% certain that less than or equal to only 15% percent of the set of records contain unrecognized non-confirming data points (test results)
15% is the Ucl (Upper confidence Level)
The Binomial Sampling tables are used for endpoints that have only two outcomes e.g., the DHR is compliant or not

26. “Top Down”     Review Design Control Procedures
Sample Design Control Records
 
Review Design Control Records
DHF

27. A “Top Down” Example...    
Design
Verification
Were Design Verification Procedures Defined? Documented?
 
Sample Design Control Records
 
Do verification activities confirm that design output meets design input requirements? Does the DHF contain the required information?
Verification
Records

28. “Vertical Probes” Design Input Design Output Design Verification
Design Validation
Design Change
Design Review
Design Transfer

30. Design Controls - Review
Establish a method for the examination of a design to determine the adequacy of the design requirements, that the design meets those requirements, and to identify problems with the design.

31. Design Controls - Verification of Outputs
Determines if manufacturer did what they intended to do.
Verifies output meets input.
Confirm by examination and provision of objective evidence that specific requirements have been met

32. Design Controls - Verification
Requirement:
Input Test/Exam Method Output

33. Design Controls - Validation
To assure that the device conforms to defined user needs and intended uses
Performed under operating conditions with initial production units or their equivalent
Actual or simulated use conditions

34. Design Controls - Transfer
To assure the product design is correctly transferred into production specifications
Procedures
Training
Documentation
Process Validation
Link to Production and Process controls

35. Corrective and Preventative Actions
CAPA often links the systems during an inspection
All inspection will include an evaluation of the CAPA system usually with a sampling of some complaint or non conformance information.

36. CAPA - Inspectional Objectives
1. Verify that CAPA system procedure(s) that address the requirements of the quality system regulation have been defined and documented.
2. Determine if appropriate sources of product and quality problems have been identified. Confirm that data from these sources are analyzed to identify existing product and quality problems that may require corrective action.

37. CAPA - Inspectional Objectives
3. Determine if sources of product and quality information that may show unfavorable trends have been identified. Confirm that data from these sources are analyzed to identify potential product and quality problems that may require preventive action.
4. Challenge the quality data information system. Verify that the data received by the CAPA system are complete, accurate and timely.
sampling tables are used

38. CAPA - Inspectional Objectives
5. Verify that appropriate statistical methods are employed (where necessary) to detect recurring quality problems. Determine if results of analyses are compared across different data sources to identify and develop the extent of product and quality problems.

39. CAPA - Inspectional Objectives
6. Determine if failure investigation procedures are followed. Determine if the degree to which a quality problem or nonconforming product is investigated is commensurate with the significance and risk of the nonconformity. Determine if failure investigations are conducted to determine root cause (where possible). Verify that there is control for preventing distribution of nonconforming product.
sampling tables are used

40. CAPA - Inspectional Objectives
7. Determine if appropriate actions have been taken for significant product and quality problems identified from data sources.
sampling tables are used
8. Determine if corrective and preventive actions were effective and verified or validated prior to implementation. Confirm that corrective and preventive actions do not adversely affect the finished device.

41. CAPA - Inspectional Objectives
9. Verify that corrective and preventive actions for product and quality problems were implemented and documented.
sampling tables are used
10. Determine if information regarding nonconforming product and quality problems and corrective and preventive actions has been properly disseminated, including dissemination for management review.

42. CAPA satellite systems
Medical Device Reporting (MDR)
sampling tables are used
Reports of Corrections and Removals (recalls)
Medical Device Tracking

43. Production & Process Controls (P&PC)

44. P&PC-Inspectional Objectives
1. Select a process for review based on:
a. CAPA indicators of process problems; b. Use of the process for manufacturing higher risk devices; c. Degree of risk of the process to cause device failures; d. The firm's lack of familiarity and experience with the process; e. Use of the process in manufacturing multiple devices; f. Variety in process technologies and Profile classes; g. Processes not covered during previous inspections; h. Any other appropriate criterion as dictated by the assignment

45. P&PC-Inspectional Objectives
2. Review the specific procedure(s) for the manufacturing process selected and the methods for controlling and monitoring the process. Verify that the process is controlled and monitored.
sampling tables are used

46. P&PC-Inspectional Objectives
3. If review of the Device History Records (including process control and monitoring records, etc.) reveals that the process is outside the firm's tolerance for operating parameters and/or rejects or that product non-conformances exist:
a. Determine whether any non-conformances were handled appropriately; b. Review the equipment adjustment, calibration and maintenance; and c. Evaluate the validation study in full to determine whether the process has been adequately validated.

47. P&PC-Inspectional Objectives
4. If the results of the process reviewed cannot be fully verified, confirm that the process was validated by reviewing the validation study.
5. If the process is software controlled, confirm that the software was validated.
The QSIT book contains a note in the Sterilization Process Controls section to verify that the manufacturer has assumed responsibility and assured the adequacy of the services of the contract sterilizer including software validation.

48. Sterilization Process Controls
Inspectional Objectives
1. Confirm that the sterilization process was validated by reviewing the validation study.
2. Review the specific procedure(s) for the sterilization process selected and the methods
for controlling and monitoring the process. Verify that the process is controlled and
monitored.
3. If review of the Device History Records (including process control and monitoring
records, acceptance activity records, etc.) reveals that the sterilization process is outside
the firm's tolerance for operating or performance parameters:
a. Determine whether the nonconformances were handled appropriately; and b. Review the equipment adjustment, calibration and maintenance
4. If the sterilization process is software controlled, confirm that the software was validated.
5. Verify that personnel have been appropriately qualified and trained to implement
the sterilization process.
I apologize for the small font size, but I wanted to show you the inspectional objectives for the auditing of the Sterilization Process Control Subsystem.
This is straight out of the QSIT handbook.
I have underlined the reference for

49. P&PC-Inspectional Objectives
6. Verify that personnel have been appropriately qualified to implement validated processes or appropriately trained to implement processes which yield results that can be fully verified.
sampling tables are used

50. P&PC-Inspectional Objectives
At the conclusion of the inspection…
7. Evaluate whether management with executive responsibility ensures that an adequate and effective quality system has been established and maintained.

51. Closing the Inspection
Management Controls (again)
Discussion With Management
Participants
No Surprises
List of Inspectional Observations (FDA-483)
Annotations (Be Prepared)
Response to FDA-483 (What Where When)

52. FDA 483 Items
From FDA Validation Study of QSIT

53. FDA-483 Annotation Reported corrected, not verified
Corrected and verified
Promised to correct
Under Consideration

54. Preparation and FDA Transparency
IOM CP
QSIT
MDR
C&R
21 CFR Part 11
CFR:
FD&C ACT
Other

55. Facilitating the Inspection
Be prepared
Department of Health and Human Services
Arrange for key employees to be available as the inspection proceeds through the QSIT sub-systems
If feasible, correct any quality system deviations during the inspection and ask for the Investigator to verify the correction
Remember, to correct the lack of an established procedure means more than just writing it. You must also implement it.
The Investigator will expect to issue the FDA-483 to the most responsible person on the premises at the conclusion of the inspection
Other key managers and professionals are invited to attend the exit interview when the FDA-483 is discussed
Send a written response to any FDA-483 to the District Director with a copy to the Investigator
Approximately days after the inspection, you should receive a copy of your Establishment Inspection Report (EIR) written by the Investigator
If there is a significant error in the EIR, then write to the District and ask for it to be corrected.

56. FDA Inspection Aspects
FDA Initiatives
Preannounced inspections
Request for records in advance
Quality Policy
Quality Manual
Quality Plan
Management Review Procedures
Annotation of FDA-483
Post Inspection letters and FMD-145

57. Presentation of History of Business Information
Organizational Charts
Who We Are and What We Make
Product Catalog, Labeling, Demos
Registration and Listing File
510(k) New Products, New Processes
Corrections to Previous FDA-483 Observations

58. Present Control of Systems/QSIT
Quality Policy and SOP Manual
Documentation of Management Review Activities
CAPA System
Record Keeping and Retrieval (Electronic Access)

59. Communication Daily Agenda Interviews Potential Observations
End of Day Recap
Briefing Management
Morning Recap and Lists

60. Adjusting the Agenda/Lists
Two Copies Please
Support for Copying Records
Pace, Breaks and Lunch
Interruptions
Minimizing Surprises

61. FDA WEB RESOURCES Medical Device Quality Systems Manual
QSIT “Guide”:
18. Factory Inspections
Guidance on Medical Device Patient Labeling; Final Guidance for Industry and FDA Reviewers

62. thank you