IMDMC FDA Regulatory 101
August 19, 2014

• A Brief History & Comparison
• The QSR Big Picture
• The Four Major QSR Subsystems
– (A break in here somewhere…)
• Documents & Records
• Back-up slides
This will be an overview presentation
This won’t be a verbatim recitation of the regulation
Personal Fit, Renewed Life
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Zimmer Holdings, Inc.

• 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
Personal Fit, Renewed Life
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Zimmer Holdings, Inc.

Part 820 - 1978
• ~5000 Words
• 159 “Shall” statements
• “Establish” –used 7 times (all tenses)
• Design Controls silent
Part 820- 1996
• ~7000 words
• 218 “Shall” statements
• “Establish” –used 71 times (all tenses)
• Design Controls – major subpart
Personal Fit, Renewed Life Zimmer Holdings, Inc.

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.
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.
Personal Fit, Renewed Life Zimmer Holdings, Inc.

Premarket
Part 812 (IDE) with
Parts 50 &56
Part 820.20
(Management
Responsibility)
Part 820.30 (Design
Controls)
Postmarket
Part 803 (MDR)
Part 806 (Corrections &
Removals) & Part 7
(Enforcement)
Part 820.100 (CAPA), 820.198
(Complaints), and 820.200
(Servicing)
Personal Fit, Renewed Life
Commercialization
Part 814 (PMA)
Part 807 (Premarket
Notification/510(k))
Part 820 (Multiple)
Zimmer Holdings, Inc.

• 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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Zimmer Holdings, Inc.

•
•
•
•
Personal Fit, Renewed Life
8 http://balancedscorecard.org
Zimmer Holdings, Inc.

Personal Fit, Renewed Life Zimmer Holdings, Inc.

Management
Responsibility
.20
Audit
• .22
Training
• .25
Quality
System
Record
.186
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Zimmer Holdings, Inc.

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– Quality Policy
– Implemented at all levels
•
– Resources – adequately trained
– “Management Representative”
•
– Review
– Audit
Zimmer Holdings, Inc.

• (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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Zimmer Holdings, Inc.

– (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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Zimmer Holdings, Inc.

• (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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Zimmer Holdings, Inc.

• 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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Zimmer Holdings, Inc.

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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Zimmer Holdings, Inc.

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• 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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Zimmer Holdings, Inc.

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Zimmer Holdings, Inc.

Personal Fit, Renewed Life Zimmer Holdings, Inc.

.70 and .75
Purchasing
.50
ID & Trace
.60 and .65
IMTE
.72
Acceptance
.80 and .86
Labeling
Packaging
.120 and
.130
HSDI
.140, .150,
.160, & .170
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Zimmer Holdings, Inc.

General
Process
Changes
Environmental
Personnel Contamination Buildings
Equipment
Manufacturing material
Automated processes
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Zimmer Holdings, Inc.

• “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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Zimmer Holdings, Inc.

• “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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Zimmer Holdings, Inc.

• 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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Zimmer Holdings, Inc.

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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Zimmer Holdings, Inc.

• 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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Zimmer Holdings, Inc.

• 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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Zimmer Holdings, Inc.

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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Zimmer Holdings, Inc.

Personal Fit, Renewed Life Zimmer Holdings, Inc.

Nonconforming
Material
CAPA
(Multiple inputs)
Servicing
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Complaints
Zimmer Holdings, Inc.

• 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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Zimmer Holdings, Inc.

• “(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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Zimmer Holdings, Inc.

– “(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.”
Personal Fit, Renewed Life
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Zimmer Holdings, Inc.

• 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
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Zimmer Holdings, Inc.

1.
Analyzing
2.
Investigating
3.
Identifying
4.
Verifying or validating
5.
Implementing and recording
6.
Ensuring …disseminated
7.
Submitting…for review Verify
Initiate
Investigate
Implement
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Zimmer Holdings, Inc.

• 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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Zimmer Holdings, Inc.

…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.
Personal Fit, Renewed Life Zimmer Holdings, Inc.

• 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
Personal Fit, Renewed Life Zimmer Holdings, Inc.

“...any written, electronic, or oral communication that alleges deficiencies related to the
– identity,
– quality,
– durability,
Which of these terms is not in the ISO 13485 definition??
– reliability,
– safety,
– effectiveness or
– performance of a device after it is released for distribution.”
Personal Fit, Renewed Life Zimmer Holdings, Inc.

Word Count
0 200 400 600
820.198 Complaints
820.100 CAPA
"Shall"
Statements
0 5 10 15
820.198 Complaints
820.100 CAPA
Personal Fit, Renewed Life
• 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”
Zimmer Holdings, Inc.

• “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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Zimmer Holdings, Inc.

• 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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Zimmer Holdings, Inc.

• “Establish” defined in Part
820.3(k)
• (k) Establish means define, document (in writing or electronically), and implement.
Define
“Say What
You Do”
Subpart D
Document
Implement
“Do What
You Say”
“Show Me
The Data”
Subpart M
Personal Fit, Renewed Life Zimmer Holdings, Inc.

Personal Fit, Renewed Life Zimmer Holdings, Inc.

Resources, Links, etc.
Personal Fit, Renewed Life Zimmer Holdings, Inc.

DHF DMR
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DHR
Zimmer Holdings, Inc.

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
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?
Personal Fit, Renewed Life Zimmer Holdings, Inc.

• 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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Zimmer Holdings, Inc.

• 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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Zimmer Holdings, Inc.