Transcript Design Controls - Indiana Medical Device Manufacturers Council

Quality System
Regulation
IMDMC FDA Regulatory 101
August 19, 2014
Agenda
• A Brief History & Comparison
• The QSR Big Picture
• The Four Major QSR Subsystems
– (A break in here somewhere…)
• Documents & Records
• Back-up slides
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This will be an
overview
presentation
This won’t be
a verbatim
recitation of the
regulation
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QSR – A Little History
• 1976 – Food, Drug, and Cosmetic Act (“The Act”)
expanded to include medical devices
– 1978 – Part 820 – Good Manufacturing Practice (GMP)
regulation for medical devices issued
• 1990 – Safe Medical Devices Act (SMDA) passed
– 1996 – Part 820 becomes the Quality System
Regulation (QSR) with expanded requirements for
medical devices
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Old QSR vs. “New” QSR
Part 820 - 1978
Part 820- 1996
• ~5000 Words
• ~7000 words
• 159 “Shall”
statements
• 218 “Shall”
statements
• “Establish” –used 7
times (all tenses)
• “Establish” –used 71
times (all tenses)
• Design Controls silent
• Design Controls –
major subpart
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Old QSR vs. “New” QSR
Complaint Files - 1978
(a) Written and oral complaints relative to the identity quality,
durability, reliability, safety, effectiveness or performance
of a device shall be reviewed, evaluated and maintained
by a formally designated unit. This unit shall determine
whether or not an investigation is necessary. When no
investigation is made, the unit shall maintain a record
that includes the reason and the name of the individual
responsible for the decision not to investigate.
(b) Any complaint involving the possible failure of a device to
meet any of its performance specifications shall be
reviewed evaluated, and investigated. Any complaint
pertaining to injury, death, or any hazard to safety shall
be immediately reviewed, evaluated, and investigated by
a designated individual(s) and shall be maintained in a
separate portion of the complaint file.
(c) When an investigation is made, a written record of each
investigation shall be maintained by the formally
designated unit identified in paragraph (a) of this section.
The record of investigation shall include the name of the
device, any control number used, name of complainant,
nature of complaint, and reply to complainant.
(d) Where the formally designated unit is located at a site
separate from the actual manufacturing establishment, a
duplicate copy of the record of investigation of any
complaint shall be transmitted to and maintained at the
actual manufacturing establishment in a file designated
for device complaints.
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Complaint Files - 1996
(a) Each manufacturer shall maintain complaint files. Each manufacturer shall establish and maintain procedures
for receiving, reviewing, and evaluating complaints by a formally designated unit. Such procedures shall
ensure that:
(1) All complaints are processed in a uniform and timely manner;
(2) Oral complaints are documented upon receipt; and
(3) Complaints are evaluated to determine whether the complaint represents an event which is required to be
reported to FDA under part 803 of this chapter, Medical Device Reporting.
(b) Each manufacturer shall review and evaluate all complaints to determine whether an investigation is
necessary. When no investigation is made, the manufacturer shall maintain a record that includes the
reason no investigation was made and the name of the individual responsible for the decision not to
investigate.
(c) Any complaint involving the possible failure of a device, labeling, or packaging to meet any of its specifications
shall be reviewed, evaluated, and investigated, unless such investigation has already been performed
for a similar complaint and another investigation is not necessary.
(d) Any complaint that represents an event which must be reported to FDA under part 803 of this chapter shall be
promptly reviewed, evaluated, and investigated by a designated individual(s) and shall be maintained in
a separate portion of the complaint files or otherwise clearly identified. In addition to the information
required by 820.198(e), records of investigation under this paragraph shall include a determination of:
(1) Whether the device failed to meet specifications;
(2) Whether the device was being used for treatment or diagnosis; and
(3) The relationship, if any, of the device to the reported incident or adverse event.
(e) When an investigation is made under this section, a record of the investigation shall be maintained by the
formally designated unit identified in paragraph (a) of this section. The record of investigation shall
include:
(1) The name of the device;
(2) The date the complaint was received;
(3) Any device identification(s) and control number(s) used;
(4) The name, address, and phone number of the complainant;
(5) The nature and details of the complaint;
(6) The dates and results of the investigation;
(7) Any corrective action taken; and
(8) Any reply to the complainant.
(f) When the manufacturer's formally designated complaint unit is located at a site separate from the
manufacturing establishment, the investigated complaint(s) and the record(s) of investigation shall be
reasonably accessible to the manufacturing establishment.
(g) If a manufacturer's formally designated complaint unit is located outside of the United States, records required
by this section shall be reasonably accessible in the United States at either:
(1) A location in the United States where the manufacturer's records are regularly kept; or
(2) The location of the initial distributor.
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Medical Devices and the CFR’s
Premarket
Postmarket
Part 812 (IDE) with
Parts 50 &56
Part 820.20
(Management
Responsibility)
Part 820.30 (Design
Controls)
Part 803 (MDR)
Part 806 (Corrections &
Removals) & Part 7
(Enforcement)
Part 820.100 (CAPA), 820.198
(Complaints), and 820.200
(Servicing)
Commercialization
Part 814 (PMA)
Part 807 (Premarket
Notification/510(k))
Part 820 (Multiple)
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QSR – Subparts as Issued
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
Subpart A--General Provisions
Subpart B--Quality System Requirements
Subpart C--Design Controls
Subpart D--Document Controls
Subpart E--Purchasing Controls
Subpart F--Identification and Traceability
Subpart G--Production and Process Controls
Subpart H--Acceptance Activities
Subpart I--Nonconforming Product
Subpart J--Corrective and Preventive Action
Subpart K--Labeling and Packaging Control
Subpart L--Handling, Storage, Distribution, and Installation
Subpart M--Records
Subpart N--Servicing
Subpart O--Statistical Techniques
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QSR – Major Subsystems
• Management
Responsibility
• Design Control
• Production and
Process Controls
• Corrective and
Preventive Action
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http://balancedscorecard.org
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MANAGEMENT
RESPONSIBILITY
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Management Responsibility Subsystem
Management
Responsibility
.20
Audit
• .22
Quality
System
Record
Training
• .25
.186
Management Responsibility
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MANAGEMENT RESPONSIBILITY
• Direction
– Quality Policy
– Implemented at all levels
• Empowerment
– Resources – adequately trained
– “Management Representative”
• Evaluation
– Review
– Audit
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Management Responsibility - I
• (a)Quality policy. ..policy and objectives for, and commitment to,
quality…understood, implemented, and maintained at all levels
of the organization.
• (b)Organization. ..adequate organizational structure to ensure
that devices are designed and produced in accordance with the
requirements of this part.
– (1)Responsibility and authority. … responsibility, authority, and
interrelation … independence and authority necessary to perform
these tasks.
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Management Responsibility - II
– (2)Resources. ..adequate resources, including the assignment of
trained personnel, for management, performance of work, and
assessment activities, including internal quality audits, to meet the
requirements of this part.
– (3)Management representative. …shall have established authority
over and responsibility for:
– (i) Ensuring that quality system requirements are effectively
established and effectively maintained in accordance with this
part; and
– (ii) Reporting on the performance of the quality system to
management with executive responsibility for review.
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Management Responsibility - III
• (c)Management review. ..review the suitability and effectiveness of the
quality system … to ensure that the quality system satisfies the
requirements of this part and the manufacturer's established quality
policy and objectives.
• (d)Quality planning. Each manufacturer shall establish a quality plan
which defines the quality practices, resources, and activities relevant
to devices that are designed and manufactured. The manufacturer
shall establish how the requirements for quality will be met.
• (e)Quality system procedures. Each manufacturer shall establish
quality system procedures and instructions. An outline of the structure
of the documentation used in the quality system shall be established
where appropriate.
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820.22 Quality audit.
• Each manufacturer shall establish procedures for quality audits
and conduct such audits to assure that the quality system is in
compliance with the established quality system requirements
and to determine the effectiveness of the quality system.
Quality audits shall be conducted by individuals who do not
have direct responsibility for the matters being audited.
• Corrective action(s), including a reaudit of deficient matters,
shall be taken when necessary. A report of the results of each
quality audit, and reaudit(s) where taken, shall be made and
such reports shall be reviewed by management having
responsibility for the matters audited. The dates and results of
quality audits and reaudits shall be documented.
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Training
Sec. 820.25 Training
• (a)General. Each manufacturer shall have sufficient personnel with the
necessary education, background, training, and experience to assure
that all activities required by this part are correctly performed.
• (b)Training. Each manufacturer shall establish procedures for
identifying training needs and ensure that all personnel are trained to
adequately perform their assigned responsibilities. Training shall be
documented.
– (1) As part of their training, personnel shall be made aware of device
defects which may occur from the improper performance of their specific
jobs.
– (2) Personnel who perform verification and validation activities shall be
made aware of defects and errors that may be encountered as part of
their job functions.
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DESIGN CONTROLS
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Design Controls
• Design Development and Planning
• Design Inputs
• Design Outputs
• Design Review
• Design Verification
• Design Validation
• Design Transfer
• Design Changes
• Design History File (DHF)
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Design Process
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PRODUCTION AND PROCESS
CONTROLS
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Process Control Subsystem
P&PC and Process Validation
.70 and .75
Purchasing
.50
ID & Trace
.60 and .65
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IMTE
.72
Acceptance
.80 and .86
Labeling
Packaging
.120 and
.130
HSDI
.140, .150,
.160, & .170
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Production and Process Controls (.70)
General
Process
Changes
Environmental
Personnel
Contamination
Buildings
Equipment
Manufacturing
material
Automated
processes
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Process Validation (.75)
• “Where the results of a process cannot be fully
verified by subsequent inspection and test, the
process shall be validated with a high degree of
assurance and approved according to established
procedures.”
• Monitoring and control procedures
– Qualified individuals
– Records – monitoring methods and data
• Changes and revalidation
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Purchasing Controls (.50)
• “Each manufacturer shall establish and maintain
procedures to ensure that all purchased or
otherwise received product and services conform
to specified requirements.”
• Supplier Evaluation
– Ability based selection
– Extent of control
– Records
• Purchasing Data
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Identification and Traceability
• Identification (.60)
– Procedures to identify throughout lifecycle
– “…to prevent mix-ups”
• Traceability (.65)
– Risk based additional requirements
– Batch numbers
– Facilitate corrective action
– Captured in DHR
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Inspection, Measuring, and Test Equipment (.72)
• IMTE Control
– Suitable and capable
– Control procedures with records
• Calibration
– Precision and accuracy limits.
– Remediation process
– Calibration standards
– Calibration records
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Acceptance Activities and Status
• Acceptance Activities (.80)
– Receiving Acceptance
– In-process Acceptance
– Final Acceptance (4 requirements for release)
– Records
• Acceptance Status (.86)
– Conformance/Nonconformance status throughout
product lifecycle
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Labeling and Packaging
• Labeling (.120)
– Label integrity
– Label Inspection
– Label Storage
– Labeling operations
– Control Number
• Packaging (.130)
– Product preservation to point of use
– Requirement touches on design and “execution”
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Handling, Storage, Distribution, & Installation
• Handling (.140) and Storage (.150)
– Prevent mix-ups and deterioration
• Distribution (.160)
– Ensure only approved, non-deteriorated devices are
shipped
– Shipment records to initial consignee
• Installation (.170)
– Accessible, adequate instructions for installation and
test
– Records to demonstrate proper installation
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CORRECTIVE & PREVENTIVE
ACTION
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CAPA Subsystem
Nonconforming
Material
CAPA
(Multiple inputs)
Servicing
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Complaints
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Corrective and Preventive Action
• Definitions (ISO 9000)
– Not defined in the QSR (820.3)
– Corrective action - action to eliminate the cause of a
detected nonconformity or other undesirable situation.
– Preventive action - action to eliminate the cause of a
potential nonconformity or other undesirable potential
situation
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Corrective and Preventive Action
• “(a) Each manufacturer shall establish and maintain
procedures for implementing corrective and preventive
action. The procedures shall include requirements for:
– (1) Analyzing processes, work operations, concessions, quality audit
reports, quality records, service records, complaints, returned product,
and other sources of quality data to identify existing and potential causes
of nonconforming product, or other quality problems. Appropriate
statistical methodology shall be employed where necessary to detect
recurring quality problems;
– (2) Investigating the cause of nonconformities relating to product,
processes, and the quality system;
– (3) Identifying the action(s) needed to correct and prevent recurrence of
nonconforming product and other quality problems;
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Corrective and Preventive Action
– “(4) Verifying or validating the corrective and preventive action to ensure
that such action is effective and does not adversely affect the finished
device;
– (5) Implementing and recording changes in methods and procedures
needed to correct and prevent identified quality problems;
– (6) Ensuring that information related to quality problems or nonconforming
product is disseminated to those directly responsible for assuring the
quality of such product or the prevention of such problems; and
– (7) Submitting relevant information on identified quality problems, as well
as corrective and preventive actions, for management review.
• (b) All activities required under this section, and their results, shall be
documented.”
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Sources of Quality Data - Analysis
•
•
•
•
•
•
•
•
•
processes,
work operations,
concessions,
quality audit reports,
quality records,
service records,
complaints,
returned product,
and other sources of
quality data…
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• …to identify existing and
potential causes of
nonconforming product,
or other quality problems.
• Appropriate statistical
methodology shall be
employed where
necessary to detect
recurring quality problems
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CAPA Verbs – 820.100
1. Analyzing
2. Investigating
Initiate
3. Identifying
Investigate
4. Verifying or validating
5. Implementing and recording
Implement
6. Ensuring …disseminated
7. Submitting…for review
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Verify
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Nonconforming Product (.90)
• Control
– Procedures address identification, documentation, evaluation,
segregation, and disposition
– Evaluation, investigation, and notification
• Review and Disposition
– Procedures establish responsibility and authority for disposition
– Justification for use of nonconforming product
– Rework control
– Retesting and re-evaluation
– Determination of adverse effects
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Complaint files (.198)
…Receiving, reviewing, and evaluating
complaints by a formally designated unit. Such
procedures shall ensure that:
– (1) All complaints are processed in a uniform and
timely manner;
– (2) Oral complaints are documented upon receipt;
– (3) Complaints are evaluated to determine whether
the complaint represents an event which is required
to be reported to FDA under part 803 of this
chapter, Medical Device Reporting.
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Complaint files, cont.
• Review and evaluate all complaints to determine
whether an investigation is necessary.
• Required investigations – allegations of failure to meet
specifications.
• Additional requirements for MDR’s
• Investigation records requirements
• Record accessibility
– Remote FDU
– Foreign establishments
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A Medical Device Complaint is...
“...any written, electronic, or oral
communication that alleges deficiencies
related to the
– identity,
– quality,
– durability,
– reliability,
– safety,
– effectiveness or
– performance
Which of these terms is
not in the ISO 13485
definition??
of a device after it is released for distribution.”
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A Brief Digression…
Word Count
0
200
400
600
820.198 Complaints
820.100 CAPA
"Shall"
Statements
0
5
10
820.198 Complaints
820.100 CAPA
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• If CAPA is more
important than
Complaint Handling,
why is the CFR section
twice as long for one as
the other??
• By specifying the resultant
work product (files), FDA
defines a process and
carves an “inspectional
path”
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Servicing (.200)
• “Where servicing is a specified requirement, each
manufacturer shall establish and maintain
instructions and procedures for performing and
verifying that the servicing meets the specified
requirements.”
• Statistical analysis
• MDR (Part 803) Connection
• Service report records
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Documents and Records
• Document Control (.40)
– Approval and distribution
– Change management
• Records – Subpart M
– General (.180)
– Device Master Record (.181)
– Device History Record (.184)
– Quality System Record (.186)
– Complaint Files (.198)
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Objective Evidence
• “Establish”
defined in Part
820.3(k)
Establish
Define
• (k)Establish
means define,
document (in
writing or
electronically),
and implement.
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Document
“Say What
Subpart D
You Do”
“Do What
You Say”
Subpart M
Implement
“Show Me
The Data”
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Why Is Objective Evidence So Important?
Quality is not explained,
it is demonstrated
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Resources, Links, etc.
BACKUP SLIDES
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Triple-D
DHF
DMR
DHR
The
development
of the
“recipe”
The
definitive
recipe
The records
of each
batch
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Complaint/AE Investigation and Resolution
Three Basic Questions
Product
Assurance
Focus - Design
Efficacy,
Durability &
Reliability
Customer
Focus Relationship
and Confidence
Restoration
Quality /
Compliance
Focus - Trend
Identification &
Corrective
Action
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1. Were the specifications
of the product fully
executed for the
complaint device?
2. Are the device
specifications adequate
for intended or
reasonable uses?
3. What is required to
restore the relationship
with the customer?
Zimmer Holdings, Inc.
Some Good Links
• Full Text of the QSR
– http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSea
rch.cfm?CFRPart=820&showFR=1
• Search page for other CFR Sections
– http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSea
rch.cfm
• CDRH Learn Course List
– http://www.fda.gov/training/cdrhlearn/default.htm
– Note: the QSR overview developed by CDRH is stored under the
“Postmarket” section
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Embedded Document
• QSR Preamble - Published when the new Part
820 was released in 1996. Records the FDA’s
deliberations in releasing this rule
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