CCAC QS Course by xiuliliaofz


									   FDA Medical Device
Quality Systems Compliance

          Quality Systems Compliance
• Introductions, Attendance Sign in
• Domestic and International Quality Systems
• Food and Drug Law
• Organization of the FDA
Break ( 15 min)
• Procedures
• FDA Quality Systems Regulations ( 21 CFR 820)
• Labeling
• Complaint Handling
• Record Keeping
Break (15 Min)
• FDA Quality Systems Audits
• Exam
• Course Evaluations

                           Quality Systems Compliance
      US and European Regulatory
           US                                            European System

Congress Passes Laws                                      European Commission
                                                            Issues Directives

FDA Writes Regulations                              Harmonized Standards adopted
                                                    by the Member Countries

Companies Develop Quality                                 Member Countries identify
   Systems Procedures                                    independent Notified Bodies

                                                    Notified Bodies Audit for
FDA Audits for Compliance                           Compliance to the Directive and
     to Regulations                                 Harmonized Standards

                            Quality Systems Compliance
        US vs European Laws
            US                                Europe
•   Food, Drug and                   • Medical Device
    Cosmetics Act                      Directive (MDD) 1993
•   Medical Device                   • Active Implantable
    Amendments (1976)                  Medical Device
•   Safe Medical Devices               Directive (AIMD) 1990
    Amendments (1990)
•   FDAMA (1997)

                     Quality Systems Compliance
      US vs. European Quality
       System Requirements
           US                                        Europe
• 21 CFR 820                       • Essential Requirements
   (Also known as the              • Harmonized Standards
     QSR)                          • ISO 13485
• Guidance Documents

                        Quality Systems Compliance
     Background of the FDA
• Biologics Control Act. 1902
• The Pure Food and Drug Act-1906
• Food Drugs and Cosmetics Act -1938
  – Medical Device Amendments to the FDCA –
  – Safe Medical Devices Act- 1990
  – FDAMA- 1997

                  Quality Systems Compliance
Offices of Medical Product Regulation within the
U.S. Food and Drug Administration (FDA)

       CBER                       CDRH                            CDER
  Center for Biologics    Center for Devices and               Center for Drug
Evaluation and Research    Radiological Health             Evaluation and Research
                              Quality Systems Compliance
 Drugs      “[an article] intended for use in the diagnosis, cure, mitigation, treatment,
            or prevention of disease . . . [or] . . . intended to affect the structure or
            any function of the body” FD&C Act, §201(g)(1)

            “. . . An instrument, apparatus, implement, machine, contrivance,
            implant, in vitro reagent, or other similar related article . . . intended for
            use in the diagnosis of disease or other conditions, or in the cure,
            mitigation, treatment or prevention of disease . . . or intended to affect
            the structure or any function of the body . . . and which does not
            achieve any of its primary intended purposes through chemical
            action within or on the body . . . and which is not dependent upon
            being metabolized for the achievement of any of its primary
            intended purposes” FD&C Act, §201(h) (emphasis added)

Biologics   “ . . .any virus, therapeutic serum, toxin, anti-toxin, vaccine, blood,
            blood component or derivative, allergenic product, or analogous
            product applicable to the prevention, treatment or cure of diseases or
            injuries” PHS Act, §351(a)

                              Quality Systems Compliance
FDA Center Responsibilities
  CBER         CDRH                           CDER

               Stethoscopes                Zocor
  Products     MRI Scanners                Viagra
  Vaccines     Hemodialysis                Tylenol
  Gene/Cell    Machines                    Celebrex
  Therapy      Surgical                    Penicillin
  Stem Cell    Instruments
  Research     Microwave
              Quality Systems Compliance
       CBER                  CDRH                           CDER

                        Devices                          Drugs
                                                         • 21 CFR 56 (IRB’s)
•21 CFR 600/601/610     •21 CFR 21 CFR
                                                         • 21 CFR 58 (GLP)
Blood                   820 QSR (GMP)
•21CFR 606              •21 CFR 56 (IRB’s)               • 21CFR 11
CLIA                                                     (Electronic records)
                        •21 CFR 58 (GLP)
21CFR 1270, 1271                                         •21 CFR 210, 211
                        •21CFR 11 (Electronic
(tissue)                                                 (Drug GMP’s)
21 CFR 58 (GLP)                                          • 21 CFR 312 (IND)
                        •21 CFRR 800-1050
21CFR 11 (electronic    (devices)                        • 21 CFR 314 (NDA)
records)                •21 CFR 807 (510(k))
                        •21 CFR 812 (IDE)

                            Quality Systems Compliance
Class Exercise - FDA Organization
    Which division of the FDA has authority over the
    following products?
•   Blood banks
•   Bandages
•   Computer terminals
•   Bone graft material
•   Pre-filled antibiotic syringes
•   Lasers for eye surgery
•   Artificial skin graft materials
•   Contact Lenses
•   Dog and Cat Food
                         Quality Systems Compliance
         Quality System
A Medical Device Quality System is
designed to assure that products are Safe
and Effective for their Intended Use
Consistently meet the specifications as
defined by results of clinical and/or
detailed technical design and validation

               Quality Systems Compliance
Quality Control

    Quality Systems Compliance
Quality Systems Compliance
   Quality System Basics (ctd)
• Quality is everyone’s responsibility
• Quality has measurable attributes
• Specifications are the  of a Quality
• Documented policy and procedures
  contribute to consistency
• Quality planning is essential

                  Quality Systems Compliance
   Quality Systems Basics (ctd)
• Clinical evaluation is the basis for safety and
• Design Controls and validation assure that
  designs meet clinical expectations and
• Process validation assures consistency
• Identification, segregation and control of
  materials and products prevents mix-ups
• Documentation control is essential
                     Quality Systems Compliance
   Quality System Basics (ctd)
• Corrective and preventative action
  systems foster continual improvement
• Labeling is important
• Internal and external (FDA) auditing
  keeps quality systems up to date

                 Quality Systems Compliance
The Documentation Pyramid

             Quality Manual


            Work Instructions

       (forms, notebooks, travelers)
           Quality Systems Compliance
                Important Terms

• Device Master Record                   • Labeling
  (DMR)-                                 • Verification
• Device History Record                  • Validation
  (DHR)                                  • Traceability
• Design History File (DHF)              • Medical Device Directive
• Technical File                           (MDD)
• Complaint                              • Essential Requirements
• Corrective Action                      • Notified Body
• Controlled Document
• Engineering Change Order

                        Quality Systems Compliance

FDA 21 CFR 820 requires
following written procedures

          Quality Systems Compliance
Group Exercise: Draw a House

         Quality Systems Compliance
                                    Draw A House
1. Read all instructions before beginning to draw the house
2. Draw your house in the lower ½ of the page
3. Begin by drawing a rectangle approximately 4 inches wide by 3 inches tall,
    with the long side parallel to the bottom edge of the paper. The bottom of the
    rectangle should be 1 inch from the bottom of the paper.
4. Locate the center of the top edge of the rectangle. Put a small dot at that point.
5. Put a small dot 1 ½ inches above the dot you just made. This dot will be
    above the rectangle.
6. Draw a line from the new dot to each edge of the top of the rectangle.
7. Draw a door in the center of the rectangle. The door should be 3/4 inch wide
    by 2 inches tall. The bottom of the door should touch the bottom of the
8. Draw a window, approximately 1 inch square on each side of the door, 1 inch
    from the bottom of the rectangle. Hint: A average thumb is about 1 inch wide
    at the knuckle. The edge of each window should be ¼ inch from the nearest
    edge of the door.
9. Draw 4 panes of glass in each window by making a cross in each window.
    Each pane should be the same size.
10. Draw a chimney on the left side of the roof of the house. The chimney should
    be parallel to the left wall of the rectangle, touching the roof. The chimney
    should be ½ inch wide by 1 inch tall and go straight up.
11. Draw some smoke coming from the chimney. A squiggly line will represent
12. Put your pencil down when you are finished.
                                   Quality Systems Compliance
     Quality System Processes
•   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

                            Quality Systems Compliance
          Management Controls
• Possible careers
  –   Internal Auditor
  –   External Auditor
  –   Quality Specialist
  –   Quality Systems

                           Quality Systems Compliance
        Who is an Auditor?

An Auditor is someone who comes in
after the war is lost to bayonet the

              Quality Systems Compliance
        Management Controls
              21CFR 820 Subpart B

•   Quality Policy Defined
•   Management Representative
•   Management Review
•   Quality Systems Procedures
•   Quality Systems Audits
•   Trained Personnel

                  Quality Systems Compliance
             Design Controls

• Possible Careers
  – Design Engineer or
  – Quality Test
  – Clinical Specialists
  – Documentation

                       Quality Systems Compliance
         Design Controls

A Medical Device Quality System is
designed to assure that products are
Safe and Effective for their Intended
Consistently meet the specifications as
defined by results of clinical and/or
detailed technical design and validation
               Quality Systems Compliance
                 Design Controls
• A Design Control System is intended to design
  products which
     •   provide safe and effective medical devices,
     •   meet the clinical needs of the intended patient population,
     •   provide outstanding value to the user,
     •   satisfy the needs and expectations of our customers.
• Phased approach to product development
• Each phase has deliverables
• Design reviews are the checkpoints

                            Quality Systems Compliance
     Design Control Elements
• 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
• Design Changes (Formal Process)
• Design History File (DHF)

                    Quality Systems Compliance
           Design Planning
• Feasibility Studies
• Risk Assessments
• Project Plan Defines Interfaces with
• Stage-Gate Methodology
• Constantly Changing

                  Quality Systems Compliance
                     Design Input
• Where
  –   Customers
  –   Technical Papers
  –   Medical experts
  –   Service people
• What
  – Intended Use
  – Technical Requirements
  – Safety Issues
• How
  –   Documented
  –   Approved
  –   Filed
  –   Formal Change Control System

                             Quality Systems Compliance
            Design Output
• Final Design Specifications
  – Quantitative
  – Documented
  – Approved
• Final Risk Assessments
• Clinical Testing May Be Needed

                   Quality Systems Compliance
         Design Reviews
• Planned Formal Technical Reviews
• Independent Member of Review Team
• Documented

               Quality Systems Compliance
    Design Verification And Validation
• Verification - Meets Specification
• Validations - Meets Intended Clinical Use
• Written Procedure Required
• Testing Must be Documented, Reviewed
  and Approved
• Software Must be Validated
• Manufacturing Processes Must be
                  Quality Systems Compliance
            Design Transfer
• Design moves from R&D to Manufacturing
• Manufacturing and Production
  Specifications are Documented
• Manufacturing IQ, OQ, PQ
  – IQ - Installation Qualification (Equipment)
  – OQ - Operational Qualification( 1st ones meet
  – PQ - Performance Qualification (Consistently
                   Quality Systems Compliance
           Design Changes
• All changes to the design after release
  must be controlled (Engineering Change
  – Re-validation may be needed
• Continues for the Life of Product

                  Quality Systems Compliance
            Design History File
• Record of the
  Development Process
  –   Plans
  –   Specifications
  –   V&V Test Results
  –   Design Reviews
  –   Changes to the Design

                       Quality Systems Compliance
Class Exercise-Design Controls
   Dr. Bright and Dr. Idea have found a novel way to produce a machine
   to determine if a heart attack patient has additional blockage in the
   coronary arteries that may be caused by the surgical bypass
   procedure (CABG). The machine non-invasively measures arterial
   flow by using Doppler sonar to determine if the arteries are blocked. It
   can be used in a patient’s home, by itself, on post heart attack
   patients who may be at risk for additional heart attacks. It transfers
   the data to a monitoring station at a EMS facility for 24/7 monitoring.

   They have formed a company (The Bright-Idea Company), built a
   prototype and tested it in the lab on sheep and pigs. It worked great.
   Now they want to begin marketing it for use on humans.

1. Is the machine a medical device?
2. What steps should Dr. Bright and Dr. Idea take before they can begin
   marketing the machine?
3. What documents do they need to have on file?

                              Quality Systems Compliance
Servicing the Product

       Quality Systems Compliance
   Manufacturing and Service

    A Medical Device Quality System is
 designed to assure that products are Safe
    and Effective for their Intended Use
Consistently meet the specifications as
   defined by results of clinical and/or
 detailed technical design and validation

                Quality Systems Compliance
         Documents Controls
• Career Opportunities
  – Documentation
    Control Specialist
  – Change Order
  – Drafter

                         Quality Systems Compliance
        Documents Controls
• Controlled System
• Review and Approval Required
  – Signature, Date
  – Authorized Personnel Listed in a Procedure
• Engineering Change Order Process (ECO)
• Electronic Records Require Special

                  Quality Systems Compliance
         Purchasing Controls
• Career Opportunities
  – Purchasing Agent
  – Buyer
  – Supplier Auditor

                       Quality Systems Compliance
        Purchasing Controls
• Written Procedures Required
• Supplier Selection Process
  – Approved Supplier List
• Purchase Orders
  – Detailed Specifications Needed
  – Supplier is Required to Have Current
• Supplier Auditing
                   Quality Systems Compliance
  Identification and Traceability
• Career Opportunities
  – Receiving and
  – Shipping Coordinators
  – Quality Technicians

                     Quality Systems Compliance
  Identification and Traceability
• Unique Identification of Product Through
  All stages of Receiving, Production,
  Installation, and Service
• Separate Accepted (Good) from Non-
  Conforming (Bad)
• Implants or Life Sustaining Product
  Requires Traceability to the User

                 Quality Systems Compliance
    Production and Process Controls

• Career Opportunities
  – Calibration Technician
  – Maintenance
  – Change Coordinators
  – Trainers
  – Process Validation

                      Quality Systems Compliance
 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
                       Quality Systems Compliance
Inspection, Measurement and Test
• Routine Calibration of Measurement
• Reference Standards Must Be Maintained
• Records Must Be Kept In Secure Areas

                Quality Systems Compliance
        Acceptance Activities
• Career Opportunities
  – Inspection Technician
  – Test Technicians
  – Non-conforming
    product coordinator

                      Quality Systems Compliance
       Acceptance Activities
• Written Procedures are Required for all
  Inspection and Test Activities
• Receiving Inspection
• In-Process Inspection and Test
• Final Inspection and Test
• Records

                  Quality Systems Compliance
     Non-Conforming Product
• Non-conforming- Def: Does not meet
• Segregation, Identification and Status of
  Nonconforming Product is Required
• Material Review Board (MRB)
• Rework, Retest and Disposition

                  Quality Systems Compliance
Typical Inspection, NCMR, and Rework Process
                   C:\ My Document s\ QA Training\

(The Happy Path)        Incoming
                        Inspect ion
                                                                                                                             Rework, Repair, Update

                        SP-00050             Special IP
                        SP-00031             IP's                                                                                FM 00032

                            Accept /
                             Reject                    Reject
                                                                            Material QA

                          St ores
                    SP00020 Material
                     control Process

                                                                                       Ret urn t o
                                                                Use As Is                              Sort / Rework                Scrap
                         In Process
                     SP 00044 Travelers
                     SP 00004 In-process
                         inspection                                            Vendor Not ificat ion
                   FM 00049 (MO)                                                   Correct ive         Reprocess
                                                                                 Act ion Request         Order
                                                                                   FM 00036
                                       Accept /
                    Scrap               Reject                                                         FM 00035
                                                                Use as is
                   FM 00043                                                   replacement
                                   Final QA                                    Debit Memo               Re-Inspect
                                   SP-00042                             FM 00029
                                                                        Debit Memo

                                       Accept /                                                            reject
                                        Reject              CPAR/ CPAN
                                                                                Receive Correcive
                                                                            Yes Action (CPAN or
                                                                                  Vendor CAR)
                                                                                                                                    Ret urn
                                                                                                                    Accept        mat erial t o
                                                                                                                                    St ores,
                                   Finished                        NO
                                                                                  Close NCMR File
                                                                                   in Quality Data

                                                  Quality Systems Compliance
  Corrective and Preventative Actions
• Career Opportunities
  – Quality Analyst
  – Quality Engineer
  – Complaint Coordinator

                     Quality Systems Compliance
  Corrective and Preventative Actions
• Includes Internal and External Actions
 (Complaints to be covered after lunch)

• Corrective Actions- Actions Taken After
  Occurrence of the Event to Prevent
  – Process Analysis
  – Failure Analysis
  – Procedure Review

                             Quality Systems Compliance
  Corrective and Preventative Actions
• Examples of Corrective Actions
  – Review of Field Failures
  – Review of NCMR
  – Procedure Reviews
• Corrective Actions Should be Validated to
  Assure They Work

                   Quality Systems Compliance
  Corrective and Preventative Actions
• Preventative Action- Actions Taken to Prevent a
  Problem from Occurring
  – Process Validations (IQ,OQ,PQ)
  – Trend Analysis of Complaints, Repairs
  – Internal Production Rework Trend Analysis
       • (NCMR DATA)
  –   Supplier Audits and Reviews
  –   Highly Accelerated Stress Screening Testing (HASS)
  –   Highly Accelerated Life Testing (HALT)
  –   Market Information Review from Competitors
                       Quality Systems Compliance
 Corrective and Preventative Actions
• Communicate the Results of Analysis
• Management Reviews must Include
  CAPA Information
• Documentation of Actions is REQUIRED
  – Indication of the effectiveness of the Quality

                    Quality Systems Compliance
        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 mis-
• Serial Numbers

                            Quality Systems Compliance
     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
• Sterile Packaging has Special
                    Quality Systems Compliance
Handling, Storage, Distribution and Installation

• Career Opportunities
  –   Material Handlers
  –   Stockroom Personnel
  –   Shipping Personnel
  –   Field Installation
  –   Traffic Managers

                      Quality Systems Compliance
           Handling, Storage,
       Distribution and Installation
• Official Release (QA) from Production to
  Storage (Stockroom) Required
• Mix-Ups Must be Prevented
• Prevention from Damage or Deterioration
  – Shelf Life
  – Stock Control-FIFO

                  Quality Systems Compliance
   Handling, Storage, Distribution and
• Procedures Required to Assure that Only
  “GOOD” Product is Released for Distribution
• Records of Following must be Kept by
  – Name and Address of Consignee (Company or
    Person who Receives Product)
  – Quantity shipped
  – Date Shipped
  – Serial, Lot Numbers Shipped

                    Quality Systems Compliance
   Handling, Storage, Distribution and
• Installation Instructions Required (IQ)
• Installation of Equipment Must Be Verified
• Records Kept (if done by Mfgr.)

                  Quality Systems Compliance
•   General
    – Records Must be Legible
    – Security maintained
    – Available for Life of Product
      •   (min) 2 years past shipping date

                       Quality Systems Compliance
• Device Master Record (DMR)( Recipe)
   –   Design Specifications
   –   Process Specifications
   –   QA Procedures
   –   Packaging Info Records
   –   Labeling Info
   –   Installation and Maintenance Info
• Device History Record (DHR)(As really Built)
   –   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
                                Quality Systems Compliance
• Career Opportunities
  – Service Technicians

                     Quality Systems Compliance
• Written Procedure For Service Required
• Testing Post Servicing Required
  – Record is part of the DHR
• Records Must Contain
  – Name and SN of Device
  – Date and Person Servicing Device
  – Service preformed and Test Results
• Service Information Must Reviewed for
                   Quality Systems Compliance
       Statistical Techniques
• Valid Statistical Plans must be used for
  all sampling and testing to verify
  conformance to specifications

                  Quality Systems Compliance
           Class Exercise
      Manufacturing and Service
The Bright-Idea Company received approval to market the machine .
They have produced approximately 1000 of the machines, shipped 700 to
their customers.

One afternoon, the final tester began to notice that the machines did not
always work the way they were supposed to at the final test station. He was
rejecting about 50% of them.

The design engineer in charge found that there was a sticky valve in about
50% of one of the lots of valves they received two months ago. It was hard
to tell if the valves would always fail or not, because the problem was

350 machines had been made using the lot with the defective valves.

You are the Quality Engineer responsible for Corrective Actions. What
steps should you take next?

                            Quality Systems Compliance
• Career Opportunities
  – Label Designer
  – Graphic Artist
  – Technical Writer

                        Quality Systems Compliance
                          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

• 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.

                                 Quality Systems Compliance
          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.
                            Quality Systems Compliance
     Prescription Device Labeling
•   Prescription Device 21 CFR 801.109
•   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.

                                     Quality Systems Compliance
        Rx Medical Device Labeling-
          General Requirements
•   Intended Use
•   Indications for Use
•   Contraindications for Use
•   Warnings, Cautions
•   Description of the Device
•   User Instructions
•   Specifications
•   Corrective Actions (Troubleshooting)
                    Quality Systems Compliance
     FDA Actions for Mislabeling
•   Warning Letters
•   Mandatory Recall
•   Injunctions to Stop Shipment
•   Seizure
•   Fines and Imprisonment

                   Quality Systems Compliance
                      FDA Legal Actions
•   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.

•   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.

•   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.

•   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.

                                           Quality Systems Compliance
     Class Exercise- Labeling

• Review of Respironics REMStar® Heated
  Humidifier labeling for:
  – Indications for use
  – Contraindications
  – Prescription Statement
  – Description
  – Corrective Actions

                   Quality Systems Compliance

  Quality Systems Compliance
         Complaint Definitions
• Any written, electronic, or oral communication
  that alleges deficiencies related to the
  – Identity
  – quality
  – durability
  – reliability
  – safety
  – effectiveness
  – or performance
  of a device after it is released for distribution."
                         Quality Systems Compliance
                    World of Complaints

                           US        EU

                                and near
                      MDR       incidents

                        Some Definitions:
Complaint: An expression of dissatisfaction concerning a product or

Quality Complaint: Any report that a product failed to meet its
specifications for intended use, safety, performance or reliability; caused
or contributed to a patient’s death; malfunctioned and could have caused
or contributed to a death, or that the labeling was misleading or
misbranding the product.

Reportable Quality Complaints
    US- Medical Device Reports- Report required if a death or serious
         injury occurred or could occur in similar circumstances due to
         a malfunction or improper labeling.

                  Quality Systems Compliance
       Sources of Complaints
Complaints that shall be processed according to
 the GMP requirements may be received from:

• Customers by letter, credit memo, returned
  goods form, or phone;
• A manufacturer's representative, or other
• The MedWatch voluntary reporting program;
• A service or repair request;
• Journal articles; or
• The FDA
                    Quality Systems Compliance
                          What to do
1. Remain Calm
2. Gather details of the complaint:
     a. Date complaint received, recipient’s name, recipient’s
         department, phone and extension number, if applicable.
     b. Complainant’s information: name, address, telephone, and fax
         number if applicable.
     c. Customer information: customer name, contact person,
         customer address, telephone, and fax number if applicable.
     d. Patient information: patient name, date product placed in
         service, date of problem/event.
     e. Device information: device name, model number, serial/lot
     f. The form of communication of complaint: written, electronic,
     g. Details of complaint: Verify that enough information has been
         given in order that an analysis can be made of the type of
         complaint, specific malfunction or deficiency of product or
         service, or problem which has occurred.
     h. If product has been returned, verify that an authorized RA
         number has been assigned
     i. If the product has not been returned, try to have the product
         placed in Quarantine by the hospital, and arrange for return
     j. Follow Up on Complaints
     k. Link to CAPA system

                          Quality Systems Compliance
• Medical Device Report (MDR)-The MDR
  regulation requires that all manufacturers
  of medical devices notify FDA when they
  become aware of a death or serious injury
  that may have been caused or
  contributed to by one of their marketed
  devices and/or any malfunction of one of
  their devices which, if it were to recur,
  would be likely to cause or contribute to a
  death or serious injury.
                  Quality Systems Compliance
          Class Exercise
Sandy Bright is Dr. Bright’s daughter. One day
she was at a neighbor’s house (Ms. Consumer)
when the machine Dr. Bright’s company made
stopped working while Ms. Consumer was using
it and Ms. Consumer had to go to the hospital.
Ms. Consumer told Sandy to tell her Dad about
the problem. Sandy told her Dad the next

What Should Dr. Bright do and when?

                 Quality Systems Compliance
FDA Audits

  Quality Systems Compliance
               FDA Audits
• Career Opportunities
  – FDA Compliance
  – FDA Consumer Safety
  – Internal Auditor                            FDA

                   Quality Systems Compliance
          FDA Audits of a Device
• Types
    – QSR-Risk Based Approach
    – Targeted- Based on a Complaint/Recall
• Establishment must be registered
• May Be Unannounced
• FDA issues a Form 482-Notice of Inspection
• If problems- FDA issues a form 483-Notice of
• Possible Warning Letter if not corrected.
                       Quality Systems Compliance
    Manufacturer’s Responsibilities
•   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”
     –   Lunch
     –   Trips to Hawaii
     –   Baseball Game Tickets
     –   Company Party

                             Quality Systems Compliance
       Employee Responsibility
•   Remain Calm
•   Answer Questions Truthfully
•   Don’t Volunteer Information
•   Refer to Procedures
•   If in Doubt, Refer to Supervisor/Escort

                    Quality Systems Compliance

Quality Systems Compliance

Quality Systems Compliance

To top