{MDQSM Excerpt - TABLE OF CONTENTS}

MEDICAL DEVICE QUALITY SYSTEMS MANUAL:

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

PREFACE

This manual covers the Quality System regulation and the basic Good Manufacturing Practices (GMP) requirements that all manufacturers and distributors must consider when they plan to manufacture medical devices, including medical device kits, trays or packs, for distribution in the United States. Model procedures and sample forms are also included in the manual to assist manufacturers.

Adherence to the medical device Quality System regulation makes good business sense and also serves public health aims -- two very good reasons for the Food and Drug Administration (FDA) to encourage compliance. However, a prerequisite to complying with a regulation is a clear understanding of its content. Recognizing this fact, the Division of Small Manufacturers Assistance (DSMA) developed this manual to help manufacturers increase their knowledge of medical device GMP requirements and FDA compliance policies. DSMA also uses this manual at quality system workshops conducted throughout the country.

The Quality System regulation outlines the minimum elements of a system for designing and producing a medical device. Manufacturers of medical devices commonly find that their quality needs are broader than these basic elements because of the additional need to meet company quality claims as required by paragraph 501(c) of the Federal Food, Drug, and Cosmetic (FD&C) Act and to meet customer needs and requirements.

The DSMA staff and the Office of Compliance (OC) in the Center for Devices and Radiological Health (CDRH) provided valuable assistance in preparing this manual.

This manual covers requirements of the Quality System regulation that manufacturers of medical devices must consider when they design devices, or when they manufacture, contract manufacture, remanufacture, process, repack, or relabel finished medical devices intended to be commercially distributed. The manual contains articles that explain the various good manufacturing practices (GMP) requirements such as design controls, process validation, calibration, device master records, component control, etc., along with related topics such as labeling. It also contains examples of forms, procedures, decals, etc. Manufacturers may use this guidance when developing their quality system.

This manual incorporates changes required by the Safe Medical Devices Act of 1990 and the Medical Device Amendments of 1992. This manual is an update of HHS publication FDA 91-4179, "Medical Device Good Manufacturing Practices Manual, Fifth Edition."  

Table of Contents:

1. The Quality System Regulation –

   1. INTRODUCTION

   2. FLEXIBILITY OF THE GMP

   3. MANUAL CONTENTS

   4. GMP APPLICATIONS AND EXEMPTIONS

                                                              i.           Exemptions

                                                            ii.           Component Manufacturers

                                                          iii.           Remanufacturers

                                                          iv.           Custom Device Manufacturers

                                                            v.           Contract Manufacturers

                                                          vi.           Contract Testing

                                                        vii.           Repackagers, Relabelers, and Specification Developers

                                                      viii.           Initial Distributors of Imported Devices

2. Quality Systems  -

   1. INTRODUCTION

   2. QUALITY SYSTEM PRACTICES

                                                              i.           Design Controls

                                                            ii.           Component Selection

                                                          iii.           Labeling Content

                                                          iv.           Process Quality

                                                            v.           Management Responsibility

                                                          vi.           Formal and Documented Quality System

                                                        vii.           Approval of Product

                                                      viii.           Quality Acceptance Activities

                                                          ix.           Quality System Audits

                                                            x.           Employee Training

3. QUALITY SYSTEM MAINTENANCE

4. MEDICAL DEVICE REPORTING

2. Design Controls  -

   1. INTRODUCTION

                                                              i.           Coverage

2. QUALITY SYSTEM

                                                              i.           Personnel Training

3. DESIGN AND DEVELOPMENT PLANNING

                                                              i.           Interface

                                                            ii.           Structure of Plans

4. DESIGN INPUT

                                                              i.           Input Checklists

5. DESIGN REVIEW

                                                              i.           Combination Devices

                                                            ii.           Preparation For Reviews

                                                          iii.           Why Design Reviews

                                                          iv.           Types Of Design Review Meetings

                                                            v.           Design Review Requirements

                                                          vi.           End Of Initial Design

6. DESIGN OUTPUT

                                                              i.           Documenting Design Output

                                                            ii.           Acceptance Criteria

                                                          iii.           Design Output Approval

7. DESIGN VERIFICATION AND VALIDATION

                                                              i.           Design Evaluation versus Specifications

                                                            ii.           Software Validation

                                                          iii.           Labeling Verification

8. DESIGN TRANSFER

9. DESIGN CHANGES

10. DESIGN HISTORY FILE

11. EXHIBITS

                                                              i.           Design Input Requirements Procedure

4. Process Validation - 

   1. INTRODUCTION

   2. TERMS AND DEFINITIONS

   3. WHY VALIDATE PROCESSES

   4. WHAT PROCESSES SHOULD BE VALIDATED

   5. TYPES OF PROCESS VALIDATION

                                                              i.           Prospective Validation

                                                            ii.           Retrospective Validation

6. PROCESS VALIDATION STUDIES

                                                              i.           Planning the Process Validation Study

                                                            ii.           Installation and Operation Qualification

                                                          iii.           Process Performance Qualification

                                                          iv.           Product Performance Qualification

7. DOCUMENTATION

8. REVALIDATION

9. REFERENCES

10. FOOTNOTES

4. Personnel  -

   1. INTRODUCTION

                                                              i.           FDA Observations

2. GMP REQUIREMENTS

                                                              i.           Employee Selection

                                                            ii.           Production Personnel

                                                          iii.           Technical Personnel

                                                          iv.           Process Validation

                                                            v.           Quality Assurance Personnel

                                                          vi.           Complaint Handling

                                                        vii.           Management

                                                      viii.           Training Methods

                                                          ix.           Training Indicators

                                                            x.           Audits

3. EXHIBITS

                                                              i.           Employee Training Procedure

                                                            ii.           Employee Training Record

6. Buildings and Environment  -

   1. INTRODUCTION

   2. PERSONNEL TRAINING

   3. BUILDINGS

                                                              i.           Repackers, Remanufacturers, Contract Sterilizers, and Relabelers

                                                            ii.           Contamination Control

                                                          iii.           Orderly Operations

4. ENVIRONMENTAL CONTROL

                                                              i.           General Controls

                                                            ii.           Analyze Operation

                                                          iii.           Specifications

                                                          iv.           Monitoring

5. CONTAMINATION CONTROL

                                                              i.           Personnel Sanitation Practices

                                                            ii.           Prevent Contamination by Hazardous Substances

                                                          iii.           Personal Practices

6. EXHIBITS

                                                              i.           Clean Room and Work Station Procedure

                                                            ii.           Cleaning Procedure for the Aseptic Filling Room

7. Equipment and Calibration  -

   1. INTRODUCTION

   2. EQUIPMENT GMP CONTROLS

                                                              i.           Maintenance

                                                            ii.           Records

3. MANUFACTURING MATERIALS

                                                              i.           Analyze Use

                                                            ii.           Control Use

4. AUTOMATED PRODUCTION AND QA SYSTEMS

                                                              i.           Software Validation Guidances

                                                            ii.           Employee Responsibility and Training

                                                          iii.           Formal Development of Software

                                                          iv.           Commercial Software and Equipment

                                                            v.           Validation of Automated Equipment and Processes

                                                          vi.           Automated Data Collection and Processing

                                                        vii.           Equipment Controls and Audits

5. MEASURING EQUIPMENT CALIBRATION

                                                              i.           Calibration Requirements Equipment Selection

                                                            ii.           Procedures

                                                          iii.           Management of Metrology

                                                          iv.           Calibration Record Schedules

                                                            v.           Standards

                                                          vi.           Calibration Environment

6. AUDIT OF CALIBRATION SYSTEM

7. INTEGRATING MEASUREMENTS INTO THE QA SYSTEM

8. EXHIBITS

                                                              i.           P.C. Board Cleaning

                                                            ii.           Calibration Procedures for Mechanical Measuring Tools

8. Device Master Record  -

   1. INTRODUCTION

                                                              i.           Document For Intended Employees

                                                            ii.           Adequate Information

                                                          iii.           Preparation and Signatures

                                                          iv.           Location of Records

                                                            v.           Record Retention

2. DEVICE MASTER RECORD CONTENTS

                                                              i.           Device Specification

                                                            ii.           Specific Documents

                                                          iii.           Records for In Vitro Diagnostic Products

3. QUALITY SYSTEM RECORD DOCUMENTS

4. WRITTEN PROCEDURES

                                                              i.           Developing Procedures

                                                            ii.           Content of Procedures

5. CHANGE CONTROL

6. EXHIBITS

                                                              i.           Documents That May Appear in a Device Master Record

                                                            ii.           Device Master Record Index

                                                          iii.           Product Specification for a Portable Defibrillator

                                                          iv.           Zener Diode Specification

                                                            v.           Label Example

                                                          vi.           Handle Assembly and Parts List

                                                        vii.           Cable Assembly and Parts List

                                                      viii.           Device Master Record Index for Amylase

                                                          ix.           Product Description

                                                            x.           Amylase Diluent Solution

                                                          xi.           Filling Record - Liquid, Non Freeze Dried

                                                        xii.           Finished Product Release Form

                                                      xiii.           Production Sample Card

                                                      xiv.           Shop Order Traveler

9. Document and Change Control  -

   1. INTRODUCTION

   2. CHANGE CONTROL PROCEDURE

                                                              i.           Identification

                                                            ii.           Effective Date

                                                          iii.           Responsibility

                                                          iv.           Revision Level

                                                            v.           Validation

                                                          vi.           Communication

                                                        vii.           Updating Documentation

                                                      viii.           Documentation Distribution

                                                          ix.           Remedial Actions

                                                            x.           Regulatory Submissions

                                                          xi.           Business Factors

3. QUALITY ASSURANCE REVIEW

4. CHANGES UNDER PREMARKET NOTIFICATION

                                                              i.           Regulatory Background

                                                            ii.           Premarket Notification Decisions

                                                          iii.           Quality System Control Always Required

5. EXHIBITS

                                                              i.           Engineering Change Policy/Procedure

                                                            ii.           Change Control Forms

10. Purchasing and Acceptance Activities  -

    1. INTRODUCTION

                                                              i.           Components

                                                            ii.           Accessory Devices

                                                          iii.           Contractors and Consultants

2. COMPONENT SELECTION AND VERIFICATION

3. PURCHASING AND RECEIVING OF PRODUCT

                                                              i.           Specifications

                                                            ii.           Supplier Qualifications

                                                          iii.           Acceptance Procedures

                                                          iv.           Acceptance Criteria

                                                            v.           Testing and Inspection of Product

                                                          vi.           Acceptance and Rejection Records

                                                        vii.           Obsolete, Deteriorated, and Rejected Components

                                                      viii.           Component Storage

                                                          ix.           Component Traceability

                                                            x.           Written Test Procedures

                                                          xi.           Sampling Plans

                                                        xii.           Control Numbers

4. CONTRACTOR AND CONSULTANT ASSESSMENTS

                                                              i.           Interface Requirements

                                                            ii.           Process Validation Requirements

                                                          iii.           Device Servicing Requirements

5. CONTRACT STERILIZATION

                                                              i.           Labeling Requirements

                                                            ii.           Quality System Requirements for Contract Sterilization

                                                          iii.           Information Transfer

                                                          iv.           Record Keeping

                                                            v.           Process Validation

                                                          vi.           Bioindicators and Dosimeters

                                                        vii.           Loading Configuration

                                                      viii.           Preconditioning

                                                          ix.           Cycle Parameters and Process Control

                                                            x.           Post-sterilization Handling and Aeration

                                                          xi.           History Records and Review

                                                        xii.           Finished Device Release

                                                      xiii.           Audits of Both Facilities

                                                      xiv.           Training

                                                        xv.           Nonconformance

6. FINISHED DEVICE EVALUATION

                                                              i.           Sampling Plans

                                                            ii.           Labeling and Packaging Inspection

                                                          iii.           Records

                                                          iv.           Product Release

7. EXHIBITS

                                                              i.           Purchase of Components

                                                            ii.           Acceptance of Components

                                                          iii.           Material Receiving and Inspection Procedure

                                                          iv.           Identification Decals and Forms

                                                            v.           Receiving Rejection Notice

11. Labeling  -

    1. LABELING REGULATIONS

                                                              i.           Misbranding

                                                            ii.           False or Misleading Labeling

                                                          iii.           Adequate Directions for Use

                                                          iv.           Prescription Devices

                                                            v.           Sterile Devices

2. DESIGN OF LABELING

                                                              i.           Write to the Reader

                                                            ii.           Refer to Actual Device

                                                          iii.           Obvious Identification of Controls

                                                          iv.           Don't Distract Reader

                                                            v.           Short and to the Point

                                                          vi.           Gobbledygook

                                                        vii.           Introduce Each Item

                                                      viii.           Accentuate Key Terms

                                                          ix.           Select Words Wisely

                                                            x.           Test Labeling

                                                          xi.           Label Integrity

                                                        xii.           Approval Policy and Procedure

                                                      xiii.           Design Transfer

                                                      xiv.           Production Controls

                                                        xv.           Receipt and Inspection

                                                      xvi.           Area Separation and Inspection

3. STORAGE

                                                              i.           Label Check and Record

                                                            ii.           Control Numbers

                                                          iii.           Access Restriction

4. CHANGES

5. SHIPPING FOR PROCESSING

6. OVER­LABELING

7. EXHIBITS

                                                              i.           Drafting and Approval of Labeling

                                                            ii.           Approval Form for Labeling, Advertising, Literature, etc.

                                                          iii.           Administration Set Label

                                                          iv.           Labeling Control Record

                                                            v.           Device History Record: OB/GYN (Plate)

                                                          vi.           User/Reader Comments

12. Product Evaluation  -

    1. INTRODUCTION

                                                              i.           Evaluation Specifications

2. CORRECTIVE AND PREVENTIVE ACTION

3. REPACKER/RELABELER DEVICE EVALUATION

4. NONCONFORMING PRODUCT

5. FAILURE INVESTIGATION

6. EXHIBITS

                                                              i.            Portable Defibrillator Test Procedure

                                                            ii.           Test DHR of a Printed Circuit Board Assembly

                                                          iii.           Device History Record (urine plate)

                                                          iv.           Batch Production Record (XLD)

                                                            v.           Batch Production Record (Thayer Martin)

                                                          vi.           Batch Production Record (Blank form)

13. Packaging  -

    1. INTRODUCTION

    2. PACKAGING DESIGN CONTROLS

                                                              i.           User Preference

3. PACKAGING MATERIALS

4. PACKAGE VALIDATION

5. PROCUREMENT, ACCEPTANCE, AND STORAGE

6. PACKAGING PROCESS

7. EXHIBITS

                                                              i.           Product Specification: Pouch

                                                            ii.           Header Bag (Specification Form)

14. Storage Distribution and Installation  -

    1. INTRODUCTION

                                                              i.           Holding and Distribution Procedures

                                                            ii.           Warehouse Storage

                                                          iii.           Distribution Records

2. DEVICE INSTALLATION

3. EXHIBITS

                                                              i.           Finished Product Release Form

                                                            ii.           Release To Finished Goods/Shipping

                                                          iii.           Product Shipping Hold

                                                          iv.           Release From Product Shipping Hold

                                                            v.           Partial List of Traceable Devices

15. Complaints  -

    1. INTRODUCTION

                                                              i.           Complaint Handling System

                                                            ii.           Complaint Responsibility

                                                          iii.           MDR Reportable Complaints

                                                          iv.           Complaint Records

                                                            v.           Investigation Records

                                                          vi.           File Accessibility and Location

                                                        vii.           Non-medical Complaints

                                                      viii.           Complaint Analysis

2. DEVICE FAILURE ANALYSIS

3. FEEDBACK FOR QA SYSTEM

4. COMPLAINT SOURCES

5. MEDICAL DEVICE REPORTING

                                                              i.           Who Must Report

                                                            ii.           When to Report

                                                          iii.           Individual Adverse Event Reports

                                                          iv.           Written MDR Procedures

                                                            v.           MDR Event Files

                                                          vi.           How to Maintain MDR Event Files

6. ADDITIONAL MDR GUIDANCE

                                                              i.           Reports of Removals and Corrections

7. EXHIBITS

                                                              i.           Complaint Processing Procedure and Forms

                                                            ii.           MedWatch Forms

16. Servicing  -

    1. INTRODUCTION

                                                              i.           Interfaces

2. SERVICE PERSONNEL

3. SERVICE REQUIREMENTS

4. INSTALLATION

5. CONTRACT SERVICE

6. SERVICE EQUIPMENT

7. SERVICE PROCEDURES

8. ACCEPTANCE STATUS

9. SERVICE REPORTS

10. SERVICE REPORT ANALYSIS

                                                              i.           Parts Shipping Trends

11. COMPLAINTS

12. CORRECTIVE AND PREVENTIVE ACTION

13. EXHIBIT

16. Quality Systems Audits  -

    1. INTRODUCTION

    2. AUDIT REQUIREMENTS

                                                              i.           Procedure

                                                            ii.           Audit Schedule

                                                          iii.           Independent Auditor

                                                          iv.           Employee Training

                                                            v.           Evaluation Criteria

                                                          vi.           Results and Corrective Actions

                                                        vii.           Audit Certification

3. EXHIBITS

                                                              i.           Policy/Procedure for Quality System Audit

                                                            ii.           Quality System Audit Procedure

                                                          iii.           Vendor Survey Form

18. Factory Inspections  -

    1. INTRODUCTION

    2. AUTHORITY AND COVERAGE

                                                              i.           Inspection Plan

                                                            ii.           Inspection Refusals

                                                          iii.           Inspection Preliminaries

                                                          iv.           Conduct During the Inspection

                                                            v.           Close-out Meeting

                                                          vi.           After the Inspection

3. BASIC POINTS FOR AN INSPECTION PLAN

4. REGULATORY SANCTIONS

                                                              i.           Adulteration

                                                            ii.           Misbranding

                                                          iii.           Management Letter

                                                          iv.           Warning Letter

                                                            v.           Seizure

                                                          vi.           Detention

                                                        vii.           Restraining Orders and Injunctions

                                                      viii.           Recalls

                                                          ix.           Penalties

5. EXHIBITS

                                                              i.           Notice of Inspection

                                                            ii.           Receipt for Samples

                                                          iii.           Affidavits

                                                          iv.           List of Observations

                                                            v.           Establishment Inspection Report

                                                          vi.           Warning Letter