Quality Systems Overview of FDAs Quality System Regulation CFR 820

1
Quality Systems Overview of FDAs Quality System
Regulation CFR 820

• U.S. Food and Drug Administration
• Center for Devices and Radiological Health

2
Harmonization of Quality System Requirements

• ISO 13485 revised reissued 2003 as a stand
  alone quality system standard for medical device
  manufacturers
• ISO 13485 2003 and 21 CFR Part 820 are
  harmonized Each may have additional
  requirements but they do not conflict with one
  another.

3
Definition Quality System

• Quality system means the organizational
  structure, responsibilities, procedures,
  processes, and resources for implementing quality
  management
• 21 CFR 820.3(v)

4
How can the QS Regulation cover so many types of
devices?

• Flexible regulation
• Requirements are stated in general terms

• Each manufacturer shall Establish and maintain a
  quality system that
• Is appropriate for the specific medical device(s)
  designed and/or manufactured
• Meets the requirements of this part (part 820)
• 21 CFR 820.5

5
7 Subsystems of the Quality System
Corrective Preventive Action Control
Design Control
Production Process Control
Management Control
Facility Equipment Control
MaterialControl
Documents, Records Change Control
6
Introduction Management Controls

• Purpose of Subsystem
• Responsibility and authority
• Quality Policy
• Organization
• Management representative
• Management review
• Quality System procedures

7
Management Control Subsystem

• Purpose
• To provide adequate resources for operations
• To monitor the quality system, make necessary
  adjustments, and assure the quality system is
  functioning properly

8
Definition Management with Executive
Responsibility

• Management with executive responsibility means
  those senior employees of the manufacturer who
  have the authority to establish or make changes
  to the manufacturers quality policy and quality
  system
• 21 CFR 820.3(n)

9
Definition Quality Policy

• Quality policy means the overall intentions and
  direction of an organization with respect to
  quality, as established by management with
  executive responsibility
• 21 CFR 820.20(u)

10
Quality Policy

• Management with executive responsibility shall
• Establish its policy and objectives for, and
  commitment to quality
• Ensure that the quality policy is understood,
  implemented, and maintained at all levels of the
  organization
• 21 CFR 820.20(a)

11
Organization

• Establish and maintain an adequate organization
  structure to ensure that devices are designed and
  produced in accordance with the requirements of
  this part.
• 21 CFR 820.20(b)

12
The Preamble on Organization

• The organizational structure should ensure that
  the technical, administrative and human factors
  functions affecting the quality of the device
  will be controlled, whether these functions
  involved hardware, software, processed materials,
  or services. All such control should be oriented
  towards the reduction, elimination, or ideally,
  prevention of quality nonconformities.
• Preamble, Comment 46

13
Appointment of Management Representative

• Management with executive responsibility shall
• Appoint a member of management as management
  representative
• Document such appointment
• 21 CFR 820.20(b)(3)

14
Management Representatives Responsibilities

• Ensure that quality system requirements are
  effectively established and effectively
  maintained in accordance with this part
• Report on the performance of the quality system
  to management with executive responsibility for
  review
• 21 CFR 820.20(b)(3)

15
Management Review

• Management with executive responsibility shall
  review the effectiveness of the quality system
• At defined intervals
• With sufficient frequency
• According to established procedures
• to ensure that the quality system satisfies the
  requirements of this part and the manufacturers
  established quality policy and objectives
• 21 CFR 820.20(c)

16
Management Review

• Document dates and results of quality system
  reviews
• Manufacturers are not required to make management
  review reports available to FDA employees during
  inspections
• Manufacturers must make procedures for management
  reviews available to FDA employees for review
  during inspections
• 21 CFR 820.20(c) 820.180(c)

17
Quality System Procedures

• Establish quality system procedures and
  instructions
• Establish an outline of the structure of the
  documentation used in the quality system where
  appropriate
• 21 CFR 820.20(e)

18
Introduction Design Controls

• Design verification
• Design validation
• Design transfer
• Design changes
• Design history file

• Purpose
• Design Planning
• Design input
• Design output
• Design review

19
Purpose of the Design Control Subsystem

• To control the design process to assure that the
  devices meet
• -User needs
• -Intended uses
• -All specified requirements, including
  regulatory requirements
• The design control requirements are not intended
  to apply to development of concepts and
  feasibility studies.
• Preamble Comment, 62

20
Design Control Scope 820.30(a)

• Design control requirements apply to
• All Class II and Class III devices
• The following class I devices
• Devices automated with computer software
• Tracheobronchial suction catheters
• Surgeon's gloves
• Protective restraints
• Manual radionuclide applicator system
• Radionuclide teletherapy source

21
Design Development Planning - 820.30(b)

• Establish and maintain plans that
• Describe or reference design and development
  activities
• Define responsibility for implementation
• Identify or describe interfaces with different
  groups or activities
• Review, update and approve plans as design and
  development evolves

22
Design Input - 820.30(c)

• Design input means the physical and performance
  requirements of a device that are used as a basis
  for device design
• Establish and maintain procedures to assure that
  device design requirements
• Are appropriate
• Address the intended use of the device
• Include in procedures a mechanism for addressing
  requirements that are
• Incomplete
• Ambiguous
• Conflicting

23
Types of Design Inputs

• Intended Use
• User Needs
• Physical characteristics
• Performance characteristic
• Safety
• Reliability
• Environmental limits

• Standards
• Regulatory requirements
• Labeling
• Human factors
• Maintenance
• Compatibility with other devices
• Sterilization

24
Design Output - 820.30(d)

• Design output means the results of a design
  effort at each design phase and at the end of the
  total design effort. The finished design output
  is the basis for the device master record. The
  total finished design output consists of the
  device, its packaging and labeling, and the
  device master record
• Establish and maintain procedures for
• Defining and documenting design output in terms
  that allow an adequate evaluation of conformance
  to design input requirements
• Containing or referencing acceptance criteria
• Ensuring design outputs essential for the proper
  functioning of the device are identified

25
In other words...

• Design output are the design specifications
  which should meet design input requirements, as
  confirmed during design verification and
  validation and ensured during design review.
• The output includes the device, its labeling and
  packaging, associated specifications and
  drawings, and production and quality assurance
  specifications and procedures.
• Preamble, comment 76

26
Design Review - 820.30(e)

• Establish and maintain procedures for design
  reviews
• Plan and conduct formal documented design reviews
  of the design results at appropriate stages
• Include at each design review
• Representatives of all functions concerned
• An individual without direct responsibility for
  the stage being reviewed
• Any specialists needed

27
Design Verification 820.30(f) vs. Design
Validation 820.30(g)
Design Verification Did I make the product
right? i.e. Specified requirements have been
fulfilled Design Validation Did I make the
right product? i.e. device specifications conform
with user needs and intended use(s)
28
Design Verification 820.30(f)

• Establish and maintain procedures for verifying
  the device design
• Confirm design output meets design input
  requirements

29
Design Validation 820.30(g)

• Establish and maintain procedures for validating
  the device design
• Perform design validation
• Under defined operating conditions
• On initial production units, lots or batches or
  their equivalents
• Under actual or simulated use conditions

30
Design Transfer 820.30(h)

• Establish and maintain procedures to ensure that
  the device design is correctly translated into
  production specifications
• FDA did not intend the requirements for Design
  Release to prohibit manufacturers from beginning
  the production process until all design
  activities have been completed.
• Preamble, comment 86

31
Design Changes - 820.30(i)

• Establish and maintain procedures for . . .
• the identification, documentation, validation or
  where appropriate verification, review, and
  approval of design changes before their
  implementation
• Minimum Design Change Requirements
• Establish design change control procedures,
  determine the risk presented by the change and
  implement design control requirements to the
  extent appropriate for that risk

32
Design History File - 820.30(j)

• Establish and maintain a design history file for
  each type of device
• Include in the DHF or reference records necessary
  to demonstrate that the design was developed in
  accordance with the design plan and part 820
  requirements
• Design history file (DHF) means a compilation of
  records which describes the design history of a
  finished device

33
Introduction Material Control

• Purpose of Subsystem
• Purchasing controls
• Statistical techniques
• Receiving, in-process, and finished device
  acceptance
• Acceptance status
• Additional Requirements

34
Material Control Subsystem

• Purpose To assure that all products that are
  accepted, used, and distributed meet
  specifications
• Products includes components, manufacturing
  materials, in-process devices, finished devices,
  and returned devices

35
Procedures for Purchasing Controls

• Establish and maintain procedures to ensure that
  all purchased or otherwise received product and
  services conform to specified requirements
• 820.50

36
Statistical Techniques

• Establish and maintain procedures, where
  appropriate, for identifying valid statistical
  techniques for establishing, controlling and
  verifying the acceptability of process capability
  and product characteristics
• 820.250(a)

37
Receiving Acceptance Activities

• General
• Establish and maintain procedures for acceptance
  of incoming product
• Inspect, test or otherwise verify that incoming
  product conforms to specified requirements
• Document acceptance or rejection
• 820.80(b)

38
In-process Acceptance Activities

• Establish and maintain acceptance procedures,
  where appropriate, to ensure that in-process
  product
• Meets specified requirements
• Is controlled until required inspections, tests
  or other verification activities have been
  completed, or necessary approvals are received
  and documented
• 820.80(c)

39
Final Acceptance Activities

• Establish and maintain procedures for finished
  device acceptance to ensure that each production
  run, lot or batch meets acceptance criteria
• Hold finished devices in quarantine or control
  them until released
• 820.80(d)

40
Final Acceptance Activities Release for
Distribution

• Conduct the following activities before releasing
  finished devices for distribution
• Complete all activities required in the DMR
• Review associated data and documentation
• Designated individual authorizes release by
  signature and date
• 820.80(d)

41
Acceptance Status

• Identify by suitable means the acceptance status
  of product to indicate conformance or
  nonconformance with acceptance criteria
• Maintain identification of acceptance status
  throughout manufacturing, packaging, labeling,
  installation, and servicing to ensure that only
  product that has passed required acceptance
  activities is distributed, used or installed
• 820.86

42
Material Control Subsystem

• Additional requirements
• Traceability 820.65
• Handling 820.140
• Storage 820.150
• Distribution 820.160

43
Introduction Documents, Record and Change Control

• Purpose of the Subsystem
• Document controls
• Records/General requirements
• Device master record
• Device history record
• Quality system record

44
Documents, Records and Change Control Subsystem

• Purpose - to assure
• Specifications and procedures are adequate
• Only current documents are used
• Changes are reviewed, approved and incorporated
  into documents
• Documents are maintained for the required length
  of time

45
Document Controls

• Establish and maintain procedures to control all
  documents required by Part 820
• Procedures shall provide for
• Document approval and distribution
• Document changes
• 21 CFR 820.40

46
Document Control - Distribution

• Documents required by Part 820 shall be available
  at all locations for which they are designated,
  used, or otherwise necessary. Remove all
  obsolete documents promptly or otherwise prevent
  their unintended use
• 21 CFR 820.40(a)

47
Records some general requirements

• Maintain all records required by Part 820 at
  manufacturing site or location that is reasonably
  accessible to manufacturer and FDA
• Make required records readily available for
  review and copying
• Records shall be legible and stored to prevent
  loss
• Retain all records required by Part 820 for the
  expected life of the device or at least 2 years
  from the date of release for commercial
  distribution -- if the device is short-lived
• 21 CFR 820.180

48
Definition Device Master Record

• Device master record (DMR) means a compilation of
  records containing the procedures and
  specifications for a finished device.
• 21 CFR 820.3(j)

49
Device Master Record

• Include in the DMR
• Device specifications
• Production process specifications
• Quality assurance procedures and specifications
• Packaging and labeling specifications
• Installation, maintenance and servicing
  procedures and methods
• 21 CFR 820.181

50
Definition Device History Record

• Device history record (DHR) means a compilation
  of records containing the production history of a
  finished device.
• 21 CFR 820.3(i)

51
Device History Record

• DHR shall include
• Dates of manufacture
• Quantity manufactured
• Quantity released for distribution
• Acceptance records which demonstrate the device
  is manufactured in accordance with DMR
• 21 CFR 820.184

52
Quality System Record

• Maintain Quality System Record (QSR)
• Prepare and approve per 21 CFR 820.40
• Include or refer to location of
• Procedures and documentation of activities
  required by Part 820 that are not specific to a
  particular type of device
• Records required by 21 CFR 820.20
• 21 CFR 820.186

53
Introduction Facility Equipment Control
Subsystem

• Purpose of Subsystem
• Design facilities that work
• Qualify equipment installation
• Maintain equipment
• Calibrate equipment
• Control environment
• Implement contamination controls

54
Facility Equipment Control Subsystem

• Purpose
• To assure that devices are not adversely
  affected by the manufacturing environment,
  buildings or equipment

55
Buildings

• Buildings should be of suitable design and
  contain sufficient space to perform necessary
  operations, prevent mixups, and assure orderly
  handling
• 21 CFR 820.70(f)

56
Equipment Installation

• Ensure that all equipment used in the
  manufacturing process meets specified
  requirements and is appropriately designed,
  constructed, placed and installed to facilitate
  maintenance, adjustment, cleaning and use.
• 21 CFR 820.70(g)

57
Equipment Requirements

• Establish and maintain equipment maintenance
  schedules and procedures.
• Conduct and document periodic inspections in
  accordance with procedures
• Post any limitations or allowable tolerances
  visibly close to equipment or make it readily
  available to persons performing periodic
  adjustment
• 21 CFR 820.70(g)(1),(2) and (3)

58
Environmental Control

• Where environmental conditions could reasonably
  be expected to have an adverse effect on product
  quality, establish and maintain procedures to
  adequately control environmental conditions
• Periodically inspect environmental control
  system(s) to verify that the system, including
  necessary equipment, is adequate and functioning
  properly
• Document and review environmental control
  activities
• 21 CFR 820.70(c)

59
Contamination Control

• Establish and maintain procedures to prevent
  contamination of equipment or product by
  substances that could reasonably be expected to
  have an adverse effect on product quality
• 21 CFR 820.70(e)

60
Introduction Production and Process Control

• Purpose of subsystem
• Manufacturing SOPs, control and monitoring
• Production and Process Changes
• Personnel practices

61
Production and Process Control

• Purpose
• to manufacture products that meet
  specifications

62
General Process Controls

• Develop, conduct, control and monitor production
  processes to ensure that a device conforms to its
  specifications
• Where deviations from device specifications could
  occur as a result of the manufacturing process,
  establish and maintain process controls necessary
  to ensure conformance to specifications.
• 21 CFR 820.70(a)

63
Production and Process Changes

• Establish and maintain procedures for changes to
  a specification, method, process or procedure.
• Verify or where appropriate validate changes
  according to 21 CFR 820.75 before implementation
• Approve changes in accordance with 21 CFR 820.40

64
Personnel Practices - Production

• Establish and maintain requirements for the
  health, cleanliness, personnel practices, and
  clothing of personnel if contact between such
  personnel and product or environment could
  reasonably be expected to have an adverse effect
  on product quality
• 21 CFR 820.70(d)

65
Introduction CAPA

• Purpose of Subsystem
• Terms, correction, corrective action and
  preventive action
• Requirements
• Preamble discussions

66
Purpose of the Corrective and Preventive Action
Subsystem

• To collect and analyze information to identify
  actual and potential product and quality problems
• To investigate product and quality problems and
  take appropriate and effective corrective or
  preventive action
• To verify or validate the effectiveness of
  corrective and preventive actions more

67
Purpose of the Corrective and Preventive Action
Subsystem

• To communicate corrective and preventive actions
  to the appropriate people
• To provide CAPA information for management review
• To document CAPA activities

68
Definition Corrective Action

• Corrective action action to eliminate the cause
  of a detected non-conformity or other undesirable
  situation.
• 1. There can be more than one cause for a
  nonconformity.
• 2. Corrective action is taken to prevent
  recurrence.
• 3. There is a difference between correction and
  corrective action.
• ISO 90002005(E)

69
Definition Correction

• Correction action to eliminate a detected
  nonconformity.
• 1. A correction can be made in conjunction with
  a corrective action.
• 2. A correction can be, for example, rework or
  regrade
• ISO 90002005(E)

70
Definition Preventive Action

• Preventive action action to eliminate the cause
  of a potential non-conformity or other
  undesirable situation
• 1. There can be more than one cause for a
  potential nonconformity.
• 2. Preventive action is taken to prevent
  occurrence.
• ISO 90002005(E)

71
CAPA Procedures

• Establish and maintain procedures for
  implementing corrective and preventive action
• Employ appropriate statistical methodology where
  necessary to detect recurring quality problems
• Investigate the cause of nonconformities relating
  to product, processes, and the quality system
• 21 CFR 820.100 more

72
CAPA Procedures

• Identify the action(s) needed to correct and
  prevent recurrence of nonconforming product and
  other quality problems
• Verify or validate the corrective and preventive
  action to ensure that such action is effective
  and does not adversely affect the finished device
  
• Implement and record changes in methods and
  procedures needed to correct and prevent
  identified quality problems
• 21 CFR 820.100 more

73
Communicating CAPA Information

• Disseminate information related to quality
  problems or nonconforming products to those
  directly responsible for assuring the quality of
  such product or the prevention of such problems
• Submit relevant information on identified quality
  problems, as well as corrective and preventive
  actions, for management review
• 21 CFR 820.100

74
The Preamble on Degree of Corrective and
Preventive Action

• FDA agrees that the degree of corrective and
  preventive action taken to eliminate or minimize
  actual or potential nonconformities must be
  appropriate to the magnitude of the problem and
  commensurate with the risks encountered. . . FDA
  does expect the manufacturer to develop
  procedures for assessing the risk, the actions
  that need to be taken for different levels of
  risk, and how to correct or prevent the problem
  from recurring, depending on that risk
  assessment.
• Preamble, Comment 159

75
The Preamble on User Error

• User error is still considered to be a
  nonconformity because human factors and other
  similar tools should have been considered during
  the design phase of the device. FDA acknowledges
  that a manufacturer cannot possibly foresee every
  single potential misuse during the design of a
  device, but when the manufacturer becomes aware
  of misuse, the corrective and preventive action
  requirements should be implemented to determine
  if redesign of the device or labeling changes may
  be necessary.
• Preamble, Comment 159

76
Inspecting CAPA Activities

• Some manufacturers try to restrict FDAs access
  to information on quality problems and
  nonconforming product by hiding CAPA activities
  in internal audits or management reviews.
  Although current procedures do not have FDA
  investigators reviewing the content of internal
  audits and management reviews specific
  information as it relates to CAPA can be viewed.

77
7 Subsystems of the Quality System
Corrective Preventive Action Control
Design Control
Production Process Control
Management Control
Facility Equipment Control
MaterialControl
Documents, Records Change Control
78
Additional Quality System requirements not
discussed

• Non-conforming product
• Labeling and Packaging Control
• Process validation
• Training
• Quality audits (Internal audits)
• Complaint Files
• Servicing

79
Summary

• Overview of 7 subsystems of Part 820 Quality
  System Regulation.
• Why comply with quality management system
  standard?