1. FDA Quality System Regulation
General Training

2. Introduction to FDA’s QSR
Quality Systems for US FDA regulated products are known as current Good Manufacturing Practices (cGMP’s).
Appropriate Quality Systems are found in the Quality System Regulations (QSR)
21 CFR Part 820, last updated and published in the Federal Register in October 1996.
It’s the LAW!
FDA QSR Overview and Training

3. Introduction to FDA’s QSR
21 CFR Part 820 is just one section of many that apply to this industry
Overall, the Food, Drug, and Cosmetic Act governs everything in our industry
The Safe Medical Devices Act of 1990 has been the latest to modernize the requirements for the medical device industry
What does the FDCA cover?
Adulteration - Fines - Inspection
Detention - Warning Letter
Injunction - Seizure - Recall
Prosecution
FDA QSR Overview and Training

4. 21 CFR Part 820 - The QSR There are 15 Subparts to the QSR
General Provisions - Quality System Requirements
Design Controls - Document Controls
Purchasing Controls - ID and Traceability
Production and Process Controls
Acceptance Activities
Nonconforming Product
Corrective and Preventive Action
Labeling and Package Control
Handling, Storage, Distribution and Installation
Records - Servicing
Statistical Techniques
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5. 21 CFR Part 820 - The QSR FDA QSR Overview and Training
Management Responsibility
Personnel and Training
Purchasing Controls
Material Controls, ID, Traceability
Installation & Service
Design Controls
Process Controls
Documentation Control
Customer
Satisfaction
CAPA
Equipment Control
Internal KPI’s, Complaints, etc.
Facility Control
Review/Analyze
Act
Acceptance Controls
Production
Contracts
FDA QSR Overview and Training

6. 21 CFR Part 820 - The QSR When FDA comes a’ callin’
An FDA inspection occurs every two years or so
It’s been over three years for us. (Who’s that knockin’ at the door?)
An FDA inspection utilizes a program called QSIT
Quality System Inspection Technique
It is a circular technique encompassing
Management Responsibility
Design Control
Corrective and Preventive Action
Production and Process Control
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7. 21 CFR Part 820 - The QSR The QSIT Circle of Control Management MDR’s
CAPA
MDR’s
Corrections and removals
Device Tracking
Design Control
Facility and Equipment Control
Material Control
Records Document Change Control
Production & Process Control
Sterilization Process Control
The QSIT Circle of Control
Management
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8. 21 CFR Part 820 - The QSR Management Responsibility
A quality policy, management review and quality audit procedures, quality plan, and quality system procedures and instructions have been defined and documented.
Quality policy and objectives have been implemented.
An organizational structure includes provisions for responsibilities, authorities and necessary resources.
A management representative has been appointed.
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9. 21 CFR Part 820 - The QSR Management Responsibility
Management reviews, including a review of the suitability and effectiveness of the quality system, are being conducted.
Quality audits, including re-audits of deficient matters, of the quality system are being conducted.
All of the above should show that...
Management with executive responsibility ensures that an adequate and effective quality system has been established and maintained.
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10. 21 CFR Part 820 - The QSR Design Controls
Lack of proper design controls is major cause of all device recalls
Intrinsic quality of devices, including their safety and effectiveness, is established during the design phase
Applies to all pre-production stages of development of Class III, II, and some Class I devices
Does not apply to development of concept and feasibility studies
Devices deemed unsafe by FDA Inspectors during inspections will be reported to CDRH
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11. 21 CFR Part 820 - The QSR Design Controls
Design Control Procedures must be established and maintained
Design and Development Planning
Design Input
Establish and maintain procedures to ensure design requirements are
Design Output
Design outputs are the design specifications that meet the design inputs
confirmed via verification and validation testing and ensured during design review
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12. 21 CFR Part 820 - The QSR Design Controls Design Verification
Design verification is the testing required to determine whether the design outputs meet functional and operational requirements of the design inputs
Design Validation
Validation follows successful verification
Verification is not a substitute for validation
Validation means establishing by objective evidence that device specifications conform with user needs and intended uses
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13. 21 CFR Part 820 - The QSR Design Controls Design Validation
Tested for performance under actual conditions or simulated use conditions or environments
Conduct such tests when changes to device design or manufacturing processes are made that could affect safety and effectiveness
Risk analysis must be conducted
Any risks judged unacceptable must be mitigated or eliminated
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14. 21 CFR Part 820 - The QSR Design Controls Design Transfer
Ensures that the design basis for the device is correctly translated into production methods and procedures
Design Changes
Applies to all design changes after initial design review that approves initial design inputs
Design History File
Contains or references all the records necessary to establish compliance with the design plan and the regulation
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15. 21 CFR Part 820 - The QSR Corrective and Preventive Action
CAPA system procedure(s) address the requirements of the quality system regulation and have been defined and documented.
Appropriate sources of product and quality problems have been identified; data from these sources are analyzed to identify existing product and quality problems that may require corrective action.
Sources of product and quality information that may show unfavorable trends have been identified and are analyzed to identify potential product and quality problems that may require preventive action.

16. 21 CFR Part 820 - The QSR Corrective and Preventive Action
Appropriate statistical methods are employed (where necessary) to detect recurring quality problems. Results of analyses are compared across different data sources to identify and develop the extent of product and quality problems.
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17. 21 CFR Part 820 - The QSR Corrective and Preventive Action
Failure investigation procedures are followed.
The degree to which a quality problem or nonconforming product is investigated is commensurate with the significance and risk of the nonconformity.
Failure investigations are conducted to determine root cause (where possible). Verify that there is control for preventing distribution of nonconforming product.
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18. 21 CFR Part 820 - The QSR Corrective and Preventive Action
Appropriate actions have been taken for significant product and quality problems identified from data sources.
Corrective and preventive actions are effective and verified or validated prior to implementation.
Corrective and preventive actions do not adversely affect the finished device.
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19. 21 CFR Part 820 - The QSR Corrective and Preventive Action
Information regarding nonconforming product and quality problems and corrective and preventive actions has been properly disseminated, including dissemination for management review.
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20. 21 CFR Part The QSR
Be careful when implementing corrective action
Without proper planning or proper judgement, the best intentions can go wrong….
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21. Nonconforming product
21 CFR Part The QSR
Corrective and Preventive Action
Product
Nonconforming product
Processes
(including audits)
Review of issue
Safety, systemic, or trend issue identified?
CAPA Investigation
KPI’s
Yes
Complaints
Quality Records
Service, installation feedback
Returned Product No
Third party information
Perform necessary actions and continue to monitor
Management Review
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22. 21 CFR Part 820 - The QSR Product and Process Controls
There’s the management stuff and the RA/QA stuff….
And then there’s the rest
These are the elements that control the day to day functions of a business
FDA QSR Overview and Training

23. 21 CFR Part 820 - The QSR Document Control
Document approval and distribution
Ensure control of the accuracy and usage of current versions of the documents
Document and data changes
Maintain change records
Approved changes must be communicated in a timely manner to appropriate personnel
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24. 21 CFR Part 820 - The QSR Purchasing Controls
Evaluate and select suppliers on the basis of their ability to meet the specified requirements.
Evaluation must be documented
Establish and maintain records of acceptable suppliers, contractors and consultants.
Purchasing Data
Approval of the purchasing data or information on the purchasing document used to purchase a product or service
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25. 21 CFR Part 820 - The QSR Identification Traceability
Ensure that all products, including manufacturing materials, used in the manufacture of finished devices are properly identified
Traceability
Establish and maintain procedures for identifying devices for surgical implant into the body with a control number, and where appropriate, components.
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26. 21 CFR Part 820 - The QSR Production and Process Controls
Intended to ensure that each manufacturer produces devices that conform to their specifications.
Where deviations from device specifications could occur, establish and maintain process control procedures that describe any process controls necessary to ensure conformance to specification
Documented instructions, SOP’s, methods
monitoring and control of process parameters and other characteristics
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27. 21 CFR Part 820 - The QSR Production and Process Changes
Establish and maintain procedures for changes to specifications, methods, process, or procedures
Verify, or where appropriate, validate changes before implementation
Environmental Control
Establish and maintain procedures where environmental conditions could reasonably be expected to have an adverse effect on product quality
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28. 21 CFR Part 820 - The QSR Personnel Contamination Control
Establish and maintain requirements for health and hygiene of personnel where such conditions could reasonably be expected to have an adverse effect on product quality
Contamination Control
Establish and maintain procedures to prevent contamination of equipment or product by any substance that could reasonably be expected to have an adverse effect on product quality
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29. 21 CFR Part 820 - The QSR Buildings Equipment
Buildings shall be of suitable design and contain sufficient space to allow for the proper manufacture of devices
Equipment
Equipment must be appropriately designed to facilitate maintenance, adjustment, cleaning, and use
Ensure that maintenance is carried out on schedule
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30. 21 CFR Part 820 - The QSR Manufacturing Material Automated Processes
Ensure removal of materials that could reasonably be expected to have an adverse effect on product quality
Maintain procedures for the use and removal of such materials
Automated Processes
Required to validate computers or automated data processing systems that are part of production or the quality system
Software used in production or quality system, whether it be in the designing, manufacturing, distributing, or tracing, must be validated
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31. 21 CFR Part 820 - The QSR Inspection, Measuring, and Test Equipment
Control of Inspection, Measuring, and Test Equipment
Establish and maintain procedures to ensure equipment is routinely calibrated, inspected, checked and maintained, and documented
Include specific directions and limits for accuracy and precision
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32. 21 CFR Part 820 - The QSR Process Validation
Where the results of a process cannot be fully verified, it shall be validated with a high degree of assurance and approved according to established procedures
Validation activities shall be documented, including date and signature
Specification Controls
Establish and maintain procedures for monitoring and control of process parameters
Validated processes are performed by qualified personnel
Revalidate when changes or process deviations occur
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33. 21 CFR Part The QSR
Receiving, In-Process and Finished Device Acceptance
Used in conjunction with Purchasing Controls to ensure suppliers, services, and contractors have the capability to provide quality product and services
Inspections and tests and other verification tools are also important to ensure components and finished devices conform to approved specifications
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34. 21 CFR Part 820 - The QSR Acceptance Status
Identify by suitable means the acceptance status of product
indicate conformance status
maintained during manufacturing, packaging, labeling, installation, and servicing of product
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35. 21 CFR Part 820 - The QSR Nonconforming Product
Control of nonconforming product
Nonconforming material must be
identified, documented, segregated, and have proper disposition
evaluation should consider the need for an investigation and notification of persons or organizations responsible for the nonconformance
The evaluation and investigation must be documented
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36. 21 CFR Part 820 - The QSR Nonconforming Product
Nonconformity review and disposition
Establish and maintain procedures that define responsibility for review and the authority for the disposition of product
Disposition is documented
include justification for use of nonconforming product (signature and date of authorizing person)
Establish and maintain procedures for rework
include re-testing and re-evaluation
rework and any determination of adverse effects shall be documented in the DHR.
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37. 21 CFR Part 820 - The QSR Labeling and Packaging Control
Establish and maintain procedures to control labeling activities
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38. 21 CFR Part 820 - The QSR Device Packaging Handling
Ensure that device packaging and shipping containers are designed and constructed to protect the device from alteration or damage during the customary conditions of processing, storage, handling, and distribution
Handling
Establish and maintain procedures to ensure that mix-ups, damage, deterioration, contamination, or other adverse effects to product do not occur during handling
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39. 21 CFR Part 820 - The QSR Distribution
Establish and maintain procedures for the control and distribution of finished devices
ensure only those devices approved for release are distributed
ensure purchase orders are reviewed to resolve ambiguities and errors before distribution
ensure expired product is not shipped
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40. 21 CFR Part 820 - The QSR Installation
Establish and maintain adequate installation and inspection instructions, and where appropriate, test procedures
Instructions shall include directions for ensuring proper installation so that the device will perform as intended
Manufacturer shall distribute the instructions and procedures with the device or otherwise make them available to the installer
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41. 21 CFR Part 820 - The QSR Installation
The person installing the device shall ensure that the installation, inspection, and any required testing are performed in accordance with the manufacturer’s instructions and procedures
The inspection and any test results shall be documented to demonstrate proper installation
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42. 21 CFR Part 820 - The QSR Records
All records required by this part shall be maintained at the manufacturing establishment or other location that is reasonably accessible
Records must be readily available for review and copying by FDA employees
Records shall be legible and stored to minimize deterioration
records stored in automated data processing systems shall be backed up
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43. 21 CFR Part 820 - The QSR Records
Records must be retained for the life of the device but in no case not less than two years from the date of release for distribution
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44. 21 CFR Part 820 - The QSR Device Master Record
The DMR is set up to contain or reference the procedures and specifications that are current on manufacturing floor for a finished device
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45. 21 CFR Part 820 - The QSR Device History Record
The DHR is the actual production records for a particular device and should be able to show the processes, tests, rework, and so on that went through from the beginning of manufacture through distribution, and if applicable, installation.
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46. 21 CFR Part 820 - The QSR Quality System Record
This section separates the procedures and documentation of activities that are not specific to a particular type of device from the device specific records
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47. 21 CFR Part 820 - The QSR Complaint Files
Establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit. The program shall ensure:
All complaints are processed in a uniform and timely manner
Oral complaints are documented upon receipt
Complaints are evaluated to determine whether the complaint represents an event which is required to reported to FDA under part 803 or (Medical Device Reporting)
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48. 21 CFR Part 820 - The QSR Complaint Files
Review and evaluate all complaints to determine whether an investigation is necessary
Determine if the complaint is valid
If valid, determine if the complaint needs to be investigated
If no investigation is required, document the justification not to investigate
justification requires signature of person making decision
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49. 21 CFR Part 820 - The QSR Complaint Files
Any complaint involving the possible failure of a device, labeling, or packaging to meet any of its specifications shall be
reviewed
evaluated
investigated
No investigation is required if a previous investigation has been conducted for a similar complaint
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50. 21 CFR Part 820 - The QSR Complaint Files
Any complaint that represents and event which must be reported under Part 803 or 804 must be promptly reviewed, evaluated, and investigated by a designated individual(s)
Records maintained in a separate portion of the complaint file or is clearly identified
Records of these investigations must include a determination of
failure to meet device specification
device used for treatment or diagnosis
relationship, if any, of the device to the reported adverse event
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51. 21 CFR Part 820 - The QSR Complaint Files
A record of each investigation must be maintained by the formally designated unit
Name of device
Date complaint was received
Device ID and any control number
Name, address, and phone no. of complainant
Nature and detail of the complaint
Dates and results of investigation
Any corrective action taken
Any reply to the complainant
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52. 21 CFR Part 820 - The QSR Complaint Files
When the formally designated complaint unit is located at a site separate from the manufacturing establishment, the investigated complaint(s) and the record(s) of the investigation shall be reasonably accessible to the manufacturing establishment
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53. 21 CFR Part 820 - The QSR Complaint Files
If the formally designated complaint unit is located outside of the US, required records must be reasonably accessible in the US at either
a location in the US where the manufacturer’s records are regularly kept
the location of the initial distributor
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54. 21 CFR Part 820 - The QSR Servicing
Where servicing is a specified requirement, establish and maintain procedures for performing and verifying that servicing meets the specified requirements
Assure that servicing is correctly performed and verified according to company specified requirements
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55. 21 CFR Part 820 - The QSR Servicing
Service shall be conducted by appropriately trained and experienced service personnel (820.25) in order to:
assure, to the extent feasible, that the process of device handling, diagnosis, and repair will not compromise the determination of the root cause of the device failure;
identify and correct the failure;
correctly report the service information; and
identify and report data related to a serious incident or adverse event.
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56. 21 CFR Part 820 - The QSR Servicing
The repair diagnosis should also try to determine, and/or provide adequate data to assist analysts in determining, the actual failure mechanism to the objective level necessary to correct or reduce the problem
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57. 21 CFR Part 820 - The QSR Servicing
Service reports must be analyzed with appropriate statistical methodology in accordance with (CAPA)
Develop sufficient trend data to make a reasonable determination as to whether corrective/preventive action is warranted
Any service report that represents a reportable event under part 803 or 804 shall automatically consider it a complaint and must be processed per
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