FDA Medical Device
Quality System Introduction
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Agenda
• Overview of FDA, Domestic and
International Quality Systems
• FDA Quality System Regulations
(21 CFR 820)
• Documentation and Records
• Labeling
• FDA Quality Systems Audits
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Introduction
This is an awareness level course
designed to provide a background of the
Quality System Regulation with a focus on
documentation, labeling, and audits.
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Offices of Medical Product Regulation within the
U.S. Food and Drug Administration (FDA)
CBER
CDRH
CDER
Center for Biologics
Evaluation and Research
Center for Devices and
Radiological Health
Center for Drug
Evaluation and Research
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US vs. European Laws
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US
Food, Drug and
Cosmetics Act
Medical Device
Amendments (1976)
Safe Medical Devices
Amendments (1990)
FDAMA (1997)
Europe
• Medical Device
Directive (MDD) 1993
• Active Implantable
Medical Device
Directive (AIMD) 1990
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US vs. European Quality System
Requirements
US
• 21 CFR 820
(Also known as the
QSR)
• Guidance Documents
Europe
• Essential
Requirements
• Harmonized
Standards
• ISO 13485
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Regulations
• 21 CFR 800-1050 (devices)
• 21 CFR 820 Quality System Regulation
(GMP—Good Manufacturing Process)
• 21 CFR 807 (510K)
• 21 CFR 812 (IDE—Investigational Device
Exemption)
• 21 CFR 814 (PMA—Premarket Approval)
• 21 CFR 11 (ERES—Electronic Records and
Electronic Signatures)
• 21 CFR 50 (Informed Consent)
• 21 CFR 56 (IRB—Institutional Review Boards)
• 21 CFR 58 (GLP—Good Laboratory
Practices)
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Quality System
A Medical Device Quality System is
designed to assure that products are Safe
and Effective for their Intended Use
and
Consistently meet the specifications as
defined by results of clinical and/or
detailed technical design and validation
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Quality Control
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Written Procedures
FDA 21 CFR 820 requires
following written procedures
Remember……
If you didn’t document it, you didn’t do it!
If you didn’t do it, DON’T document it!
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The Documentation Pyramid
Quality Manual
Procedures
Work Instructions
Records
(forms, notebooks, travelers)
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Quality System Processes
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Management Controls
Design Controls
Materials Controls
Document Controls
Purchasing Controls
Production and
Process Controls
• Facilities and
Equipment Controls
• Document, Record
and Change Controls
• Corrective and
Preventative Action
• Labeling Controls
• Handling, Storage,
and Distribution
controls
• Servicing Controls
• Statistical Techniques
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Important Terms
• Device Master
Record (DMR)• Device History
Record (DHR)
• Design History File
(DHF)
• Technical File
• Complaint
• Corrective Action
• Controlled
Document
• Engineering Change
Order (ECO)
• Labeling
• Verification
• Validation
• Traceability
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Design Control Elements
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Design Planning
Design Input (Requirements)
Design Output (Specifications)
Design Reviews (Technical)
Design Verification (Meets Specifications
Design Validation (Meets clinical needs)
Design Transfer- (Moves from Design to
Manufacturing)
• Design Changes (Formal Process)
• Design History File (DHF)
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Document Controls
• Controlled System
• Review and Approval Required
– Signature, Date
– Authorized Personnel Listed in a
Procedure
• Engineering Change Order Process
(ECO)
• Electronic Records Require Special
Security
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Production and Process Controls
• Written Instructions (SOP’s) Required
• Environmental Controls
– Clean Rooms
• Personnel
– Health, Cleanliness, etc.
• Contamination Control
• Equipment
– Maintenance Schedules
– Software Validation Required in Process Equipment
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Records
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General
– Records Must be Legible
– Security maintained
– Available for Life of Product
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(min) 2 years past shipping date
– Should be an ongoing process in real time
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Records
• Device Master Record (DMR)( Recipe)
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Design Specifications
Process Specifications
QA Procedures
Packaging Info Records
Labeling Info
Installation and Maintenance Info
• Device History Record (DHR)(As really Built)
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Date of Manufacture
Quantity Manufactured
Quantity Released for Distribution
Acceptance ( Test) Records
Primary Labeling Information
• Quality System Record (QSR)
– Quality Manual, Management Review Procedures, SOP’s, Generic
Training Procedures, Other Non-device Specific Quality Procedures
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Labeling
• We will focus on labeling for commercial
devices.
• Labeling is different for a commercial
device versus an investigational device.
• Follow all policies and procedures
regarding labeling requirements.
• Ensure that the label on the device
matches the label on the outer
packaging.
– Follow specific work instructions for labeling
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Labeling and Packaging
• Written Procedures Required
• Label Integrity– Does the label remain legible for product life
• Label Inspection
– Control of labels required
• Label Storage
– Secure area
– QA release
• Labeling Operations
– Assure that labels are not mixed up
– Recalls of FDA regulated product can be initiated by mislabeling
• Serial Numbers
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Labeling and Packaging
• Packaging must be Designed to Assure
That Products Are Protected During
Transit and Storage
– Shipping testing
– Environmental testing (Temperature, Humidity)
– Specialized labeling of the package may be
needed
• Sterile Packaging has Special
Considerations
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Labeling
21 CFR 801
• Section 201(k) defines "label" as a:
"display of written, printed, or graphic matter upon the immediate
container of any article..." The term "immediate container" does not
include package liners. Any word, statement, or other information
appearing on the immediate container must also appear "on the
outside container or wrapper, if any there be, of the retain package of
such article, or is easily legible through the outside container of
wrapper."
• Section 201(m) defines "labeling" as:
"all labels and other written, printed, or graphic matter
(1) upon any article or any of its containers or wrappers, or
(2) accompanying such article" at any time while a device is held for sale after
shipment or delivery for shipment in interstate commerce.
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Over The Counter (OTC)
Device Labeling
• Principal Display Panel 21 CFR 801.60
The principal display panel is that portion of the label which is
intended to be displayed, presented, shown, or examined under
customary conditions for retail sales.
• Statement of Identity 21 CFR 801.61
The statement of identity of the device must be listed on the
principal display panel.
– It must list the common name
– Indications for use
– Bold type,
– Reasonably sized generally parallel to the base of the package
• Net Quantity of Contents Statement 21 CFR 801.62
The label of an over-the-counter (OTC) device in package form must
contain a statement of net quantity of contents in terms of weight,
measure, numerical count; or a combination of numerical count and
weight, measure.
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Prescription Medical Device
Labeling- General Requirements
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Intended Use
Indications for Use
Contraindications for Use
Warnings, Cautions
Description of the Device
User Instructions
Specifications
Corrective Actions (Troubleshooting)
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Prescription Device Labeling
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Prescription Device 21 CFR 801.109
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A device which, because of any potentiality for harmful effect, or the supervision of
the method of its use, or the collateral measures necessary to its use is not safe
unless under a practitioner licensed by law to direct use this device, and hence for
which "adequate directions for use" cannot be written, is exempt from such provided:
– - It is in the possession of either a licensed practitioner or persons lawfully
engaged in the manufacture of distribution of the product;
– - Its labeling bears an Rx statement, i.e., "Caution: Federal law restricts this
device to sale by or on the order of a (Insert name of physician, dentist or other
licensed practitioner;"
– - Its labeling bears information for use including, indications, effects, routes,
methods, and frequency and duration of administration, and any relevant
hazards, contraindications, side effects, and precautions under which the device
can safely be used; and
– - All labeling other than labels and carton bears the date of issuance or date of
the latest revision.
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Labeling for Investigational Devices
• Current Good Manufacturing Practice (cGMP—21 CFR
820)
– Or waiver
• Good Clinical Practices (GCP) Label Requirements – 21
CFR 812.5
– Caution—Investigational device. Limited by Federal or U.S. law
to investigational use.
– Describe all relevant contraindications, hazards, adverse effects,
interfering substances or devices, warnings, and precautions.
– No false or misleading information.
– Cannot represent device as safe or effective for purpose for
which it is being investigated.
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FDA Actions for Mislabeling
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Warning Letters
Mandatory Recall
Injunctions to Stop Shipment
Seizure
Fines and Imprisonment
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FDA Legal Actions
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SEC. 303. [21 U.S.C. 333] (a)(1) Any person who violates a provision of section 301 shall be
imprisoned for not more than one year or fined not more than $1,000, or both.
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Notwithstanding the provisions of paragraph (1) of this section, if any person commits such a
violation after a conviction of him under this section has become final, or commits such a violation
with the intent to defraud or mislead, such person shall be imprisoned for not more than three
years or fined not more than $10,000 or both.
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Knowingly distributing drugs/devices in violation of section 503(e)(2)(A), shall be imprisoned for
not more than 10 years or fined not more than $250,000, or both.
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Any manufacturer or distributor who distributes drug/device samples by means other than the mail
or common carrier whose representative, during the course of the representative’s employment or
association with that manufacturer or distributor, violated section 301(t) because of a violation of
section 503(c)(1) or violated any State law prohibiting the sale, purchase, or trade of a drug
sample subject to section 503(b) or the offer to sell, purchase, or trade such a drug sample shall,
upon conviction of the representative for such violation, be subject to the following civil penalties:
(A) A civil penalty of not more than $50,000 for each of the first two such violations resulting in a
conviction of any representative of the manufacturer or distributor in any 10-year period.
(B) A civil penalty of not more than $1,000,000 for each violation resulting in a conviction of any
representative after the second conviction in any 10-year period.
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FDA Audits/Inspections
• Types
– QSR-Risk Based Approach
– Targeted- Based on a Complaint/Recall
• Establishment must be registered
• May Be Unannounced
• Inspector presents Form 482-Notice of
Inspection and badge
• Sponsor must give access to the records
and allow copying of records
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FDA
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Things not to do
when FDA audits…
Run away and hide until they leave.
Tell them you don’t really work here, you are just
visiting and point to your co-worker to handle it.
Refuse to let them in, noting your policy of not
seeing anyone without an appointment.
Tell them the building is infested with bees and it
would be too risky for them to enter.
Tell them there must be some mistake, they
have the wrong business and give them the
address of a competitor.
Tell them you are under a doctor’s care for
amnesia.
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What should you do
when FDA audits?
FDA audits are generally unannounced.
Be prepared for unannounced audits by
knowing the company policy for FDA
audits.
Ensure that you are always complying with
regulations and specific policies and
procedures so that you are prepared in the
event of an audit.
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Employee Responsibility
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Remain Calm
Answer Questions Truthfully
Don’t Volunteer Information
Refer to Policies and Procedures
If in Doubt, Refer to Supervisor/Escort
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Manufacturer’s Responsibilities
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Have Written Policy for FDA or other External Audits
Have Records Organized
Have an Escort at all Times
Have a Separate Room for the Auditor
Bring Information to Auditor
Be Courteous
Don’t offer any “bribes”
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Lunch
Trips to Hawaii
Baseball Game Tickets
Company Party
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FDA Inspection
• If problems- FDA issues a form 483-Notice
of Observations
• Deviations from guidance documents
noted in Establishment Inspection Report
(EIR)
• Possible Warning Letter if not corrected
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Summary
• FDA regulations must be followed in the device
manufacturing process.
• Proper labeling is required; follow all company
policies and procedures
– Read instructions carefully
– Do not make unauthorized changes in processes
• Document all required information in appropriate
places.
• Store records in the required manner, for the
required time period, and in an appropriate area.
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Questions
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References
• FDA Website, www.fda.gov/cdrh
• 21 CFR 820
• FDA Publication, Device Advice
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