Title: Quality Systems Overview of FDAs Quality System Regulation CFR 820
1Quality Systems Overview of FDAs Quality System
Regulation CFR 820
- U.S. Food and Drug Administration
- Center for Devices and Radiological Health
2Harmonization 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.
3Definition Quality System
- Quality system means the organizational
structure, responsibilities, procedures,
processes, and resources for implementing quality
management - 21 CFR 820.3(v)
4How 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
57 Subsystems of the Quality System
Corrective Preventive Action Control
Design Control
Production Process Control
Management Control
Facility Equipment Control
MaterialControl
Documents, Records Change Control
6Introduction Management Controls
- Purpose of Subsystem
- Responsibility and authority
- Quality Policy
- Organization
- Management representative
- Management review
- Quality System procedures
7Management 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
8Definition 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)
9Definition 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)
10Quality 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)
11Organization
- 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)
12The 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
13Appointment 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)
14Management 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)
15Management 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)
17Quality 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)
18Introduction Design Controls
- Design verification
- Design validation
- Design transfer
- Design changes
- Design history file
- Purpose
- Design Planning
- Design input
- Design output
- Design review
19Purpose 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
20Design 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
21Design 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
22Design 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
23Types 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
24Design 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
25In 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
26Design 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
27Design 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)
28Design Verification 820.30(f)
- Establish and maintain procedures for verifying
the device design - Confirm design output meets design input
requirements
29Design 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
30Design 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
31Design 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
32Design 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
33Introduction 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
35Procedures for Purchasing Controls
- Establish and maintain procedures to ensure that
all purchased or otherwise received product and
services conform to specified requirements - 820.50
36Statistical 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)
37Receiving 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)
38In-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)
39Final 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)
40Final 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)
41Acceptance 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
42Material Control Subsystem
- Additional requirements
- Traceability 820.65
- Handling 820.140
- Storage 820.150
- Distribution 820.160
43Introduction Documents, Record and Change Control
- Purpose of the Subsystem
- Document controls
- Records/General requirements
- Device master record
- Device history record
- Quality system record
44Documents, 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
45Document 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
46Document 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)
47Records 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
48Definition 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)
49Device 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
50Definition 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)
51Device 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
52Quality 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
53Introduction Facility Equipment Control
Subsystem
- Purpose of Subsystem
- Design facilities that work
- Qualify equipment installation
- Maintain equipment
- Calibrate equipment
- Control environment
- Implement contamination controls
54Facility Equipment Control Subsystem
- Purpose
- To assure that devices are not adversely
affected by the manufacturing environment,
buildings or equipment
55Buildings
- 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)
56Equipment 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)
-
57Equipment 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)
58Environmental 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)
59Contamination 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)
60Introduction Production and Process Control
- Purpose of subsystem
- Manufacturing SOPs, control and monitoring
- Production and Process Changes
- Personnel practices
61Production and Process Control
- Purpose
- to manufacture products that meet
specifications
62General 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)
63Production 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
64Personnel 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)
65Introduction CAPA
- Purpose of Subsystem
- Terms, correction, corrective action and
preventive action - Requirements
- Preamble discussions
66Purpose 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
67Purpose 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
68Definition 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)
69Definition 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)
70Definition 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)
71CAPA 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
72CAPA 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
73Communicating 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
-
74The 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
75The 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
76Inspecting 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.
777 Subsystems of the Quality System
Corrective Preventive Action Control
Design Control
Production Process Control
Management Control
Facility Equipment Control
MaterialControl
Documents, Records Change Control
78Additional Quality System requirements not
discussed
- Non-conforming product
- Labeling and Packaging Control
- Process validation
- Training
- Quality audits (Internal audits)
- Complaint Files
- Servicing
79Summary
- Overview of 7 subsystems of Part 820 Quality
System Regulation. - Why comply with quality management system
standard?