Computer systems validation: quality assurance, risk management and regulatory compliance for pharmaceutical and healthcare companies

ph1871fm.pdf......Page 1
Computer Systems Validation: Quality Assurance, Risk Management, and Regulatory Compliance for Pharmaceutical and Healthcare Companies......Page 2
Foreword......Page 6
REFERENCES......Page 7
Preface......Page 9
The Editor......Page 10
Contributor Biographies......Page 11
Abbreviations......Page 22
Contents......Page 32
Table of Contents......Page 0
CONTENTS......Page 35
TODAY’S COMPUTING ENVIRONMENT......Page 36
RUDIMENTARY COMPUTER SYSTEM CHARACTERISTICS......Page 37
PROBLEMS IN IMPLEMENTING COMPUTER SYSTEMS......Page 38
QUALITY ASSURANCE......Page 39
GXP PHILOSOPHY......Page 40
VALIDATION......Page 41
Keeping Current......Page 42
BUYER BEWARE......Page 43
MISCONCEPTIONS......Page 44
COST OF FAILURE......Page 45
MEASURING SUCCESS......Page 47
PERSISTENT REGULATORY NONCOMPLIANCE......Page 49
REFERENCES......Page 51
CONTENTS......Page 53
GOOD MANUFACTURING PRACTICE (GMP)......Page 54
GOOD DISTRIBUTION PRACTICE (GDP)......Page 57
GOOD LABORATORY PRACTICE (GLP)......Page 58
MEDICAL DEVICES......Page 59
ELECTRONIC RECORDS AND ELECTRONIC SIGNATURES (ERES)......Page 60
COLLECTIVE GXP REQUIREMENTS......Page 62
PMA’S CONCEPT PAPER......Page 64
PHRMA’S COMPUTER VALIDATION KEY PRACTICES......Page 65
GAMP INFRASTRUCTURE AND PDA NETWORK GUIDANCE......Page 66
GAMP 4......Page 67
PDA/ISPE GOOD PRACTICE AND COMPLIANCE FOR PART 11......Page 68
PIVOTAL INSPECTION INCIDENTS......Page 69
REFERENCES......Page 74
CONTENTS......Page 78
ORGANIZATIONAL RESPONSIBILITIES......Page 79
COMPLIANCE STRATEGY......Page 80
Personnel......Page 81
Self-Inspections, Managing Deviations and Continuous Improvement......Page 82
VALIDATION POLICY......Page 83
OPERATION......Page 84
COMPUTER SYSTEMS INVENTORY......Page 86
GETTING STARTED......Page 88
RISK MANAGEMENT......Page 90
Laboratory Control Systems......Page 91
LIFE-CYCLE APPROACH......Page 93
MANAGEMENT REVIEW......Page 94
RESOURCE PLANNING......Page 95
REFERENCES......Page 97
PROJECT REQUIREMENTS......Page 99
RESPONSIBILITIES AND ACCOUNTABILITIES......Page 100
CONTENTS......Page 102
QUALIFICATIONS......Page 103
TRAINING PLANS AND RECORDS......Page 104
DOCUMENT PREPARATION......Page 105
DOCUMENT REVIEW......Page 106
DOCUMENT ISSUE......Page 108
DOCUMENT ADMINISTRATION AND STORAGE......Page 109
QUALITY OF DOCUMENTATION......Page 110
CHANGE CONTROL......Page 111
REQUEST FOR CHANGE......Page 112
CHANGE EVALUATION (IMPACT ANALYSIS) AND AUTHORIZATION......Page 113
RECENT INSPECTION FINDINGS......Page 115
CONFIGURATION MANAGEMENT......Page 116
CONFIGURATION EVALUATION......Page 117
SELF-INSPECTIONS (INTERNAL AUDITS)......Page 118
MANAGING DEVIATIONS......Page 119
REFERENCES......Page 121
APPENDIX 4A: EXAMPLES OF DEFICIENT DOCUMENTARY EVIDENCE......Page 122
APPENDIX 4B: EXAMPLE SELF-INSPECTION CHECKLIST......Page 123
CONTENTS......Page 126
CHARACTER OF APPLICATION......Page 127
COTS PRODUCTS......Page 128
OPEN SOURCE SOFTWARE......Page 129
APPROACH TO VALIDATION......Page 130
MANAGING CHANGE......Page 132
VALIDATION ROLES......Page 133
CHOOSING AN APPROPRIATE LIFE-CYCLE METHODOLOGY......Page 134
VALIDATION (MASTER) PLANNING......Page 137
USER REQUIREMENTS SPECIFICATION (URS)......Page 138
SUPPLIER SELECTION......Page 139
SYSTEM OVERVIEW......Page 140
DATA DEFINITION (INCLUDING CONFIGURATION)......Page 141
CODING, CONFIGURATION, AND BUILD......Page 142
DEVELOPMENT TESTING......Page 143
PREDELIVERY INSPECTION......Page 144
OPERATIONAL QUALIFICATION (OQ)......Page 145
OPERATION AND MAINTENANCE PREREQUISITES......Page 146
DOCUMENT MANAGEMENT......Page 148
DEVIATION MANAGEMENT......Page 149
REVIEWS AND APPROVALS......Page 150
REFERENCES......Page 154
CONTENTS......Page 155
PROJECT SCOPE......Page 156
PROJECT RISK MANAGEMENT......Page 157
PROJECT AND QUALITY PLANS......Page 158
EARLY INDICATION OF VALIDATION REQUIREMENT......Page 159
VALIDATION DETERMINATION STATEMENT......Page 160
CONTENTS OF VALIDATION MASTER PLAN......Page 161
STRUCTURE OF VALIDATION MASTER PLAN......Page 162
PREPARATION OF A VALIDATION MASTER PLAN......Page 163
CONTENTS OF A VALIDATION PLAN......Page 164
STRUCTURE OF A VALIDATION PLAN......Page 165
Validation Life Cycle......Page 166
Supplier and Subcontractor Management......Page 167
SUPPLIER RELATIONSHIPS......Page 168
Availability of Software and Reference Documentation......Page 169
APPROACH TO HARDWARE......Page 170
GAMP Category 3 Software: Standard Software Packages......Page 171
GAMP Category 4 Software: Configurable Software Packages......Page 172
CRITICALITY–IMPACT ANALYSIS......Page 173
MANAGING COMPLIANCE ISSUES......Page 174
REFERENCES......Page 175
APPENDIX 6A: EXAMPLE VALIDATION DETERMINATION STATEMENT......Page 176
Appendices......Page 177
Document Review and Approvals......Page 178
Appendices......Page 179
CONTENTS......Page 180
CONTENTS......Page 181
GXP ASSESSMENTS......Page 184
IDENTIFYING GXP PROCESSES AND FUNCTIONS......Page 185
IDENTIFYING CRITICAL COMPONENTS AND DEVICES......Page 186
REGULATORY EXPECTATIONS......Page 188
PROPOSAL EVALUATION......Page 189
APPLICABILITY......Page 191
ISO 9000 Accredited Suppliers......Page 193
Postal Audits......Page 194
CONDUCTING AUDITS......Page 195
Subcontractors......Page 196
AUDIT REPORT AND FOLLOW-UP......Page 197
PREFERRED SUPPLIERS......Page 198
USER GROUPS......Page 199
REFERENCES......Page 200
Design Constraints......Page 201
Documentation......Page 202
Appendices......Page 203
Audit Follow-Up......Page 204
APPENDIX 7C: EXAMPLE POSTAL SUPPLIER AUDIT QUESTIONNAIRE......Page 205
APPENDIX 7D: EXAMPLE SUPPLIER AUDIT CHECKLIST......Page 206
Audit Outcome......Page 208
Appendices......Page 209
CONTENTS......Page 210
SUPPLIER PROJECT AND QUALITY PLANS......Page 211
CONTENT......Page 212
ANTICIPATING TESTING......Page 213
CONTENTS......Page 215
ARCHITECTURAL DESIGN......Page 217
SOFTWARE DESIGN......Page 218
HARDWARE DESIGN......Page 220
DEALING WITH COTS SOFTWARE AND HARDWARE......Page 221
DESIGN REVIEW (INCLUDING HAZARD STUDY)......Page 222
HAZARD ANALYSIS AND CRITICAL PROCESS POINT (HACCP)......Page 223
COMPUTER HAZARD AND OPERABILITY (CHAZOP) STUDY......Page 224
FAILURE MODE EFFECT ANALYSIS (FMEA)......Page 226
RECENT INSPECTION FINDINGS......Page 232
PROTOTYPING......Page 233
EXTREME PROGRAMMING......Page 234
REFERENCES......Page 235
Appendices......Page 237
Process Control......Page 238
Operational Environment......Page 239
Appendices......Page 240
Appendices......Page 241
APPENDIX 8E: EXAMPLE HAZARD STUDY QUESTIONS (BASED ON VALIDATING AUTOMATED MANUFACTURING)......Page 242
SOFTWARE PROGRAMMING......Page 245
PROGRAMMING APPROACH......Page 246
REDUNDANT CODE (“DEAD CODE”)......Page 247
RECENT INSPECTION FINDINGS......Page 248
SOURCE CODE REVIEW......Page 249
ANNOTATED SOFTWARE LISTING......Page 250
REPORTING......Page 251
ACCESS TO APPLICATION CODE......Page 254
SYSTEM ASSEMBLY......Page 255
REFERENCES......Page 256
Change History......Page 257
Program Documentation......Page 258
General Practices......Page 259
Output Labeling......Page 260
Review Follow-Up......Page 261
CONTENTS......Page 262
TEST PLANS......Page 263
Test Method......Page 264
TEST CONDITIONS......Page 265
TEST OUTCOME......Page 267
TEST REPORTING......Page 268
RECENT INSPECTION FINDINGS......Page 269
STRUCTURAL (WHITE BOX) TESTING......Page 270
INSPECTION EXPERIENCE......Page 271
FUNCTIONAL (BLACK BOX) TESTING......Page 272
PREDELIVERY INSPECTION......Page 273
REFERENCES......Page 274
Appendices......Page 276
Observations......Page 277
CONTENTS......Page 278
QUALIFICATION......Page 279
TEST DOCUMENTATION......Page 281
TEST ENVIRONMENT......Page 283
LEVERAGE DEVELOPMENT TESTING......Page 284
RECENT INSPECTION FINDINGS......Page 286
CALIBRATION......Page 287
DATA MAPPING......Page 290
DATA VERIFICATION......Page 291
INVENTORY CHECKS......Page 292
OPERATIONAL QUALIFICATION......Page 293
TEST REDUCTION......Page 294
RECENT INSPECTION FINDINGS......Page 295
PRODUCT PERFORMANCE QUALIFICATION......Page 296
PROCESS PERFORMANCE QUALIFICATION......Page 297
VALIDATION REPORT......Page 298
VALIDATION SUMMARY REPORT......Page 300
RECENT INSPECTION FINDINGS......Page 301
REFERENCES......Page 303
Test Procedure Execution......Page 304
References......Page 305
Scope......Page 306
SCOPE......Page 307
Scope of Process PQ......Page 308
Document Review and Approvals......Page 309
Appendices......Page 310
CONTENTS......Page 311
Applications......Page 313
RECENT INSPECTION FINDINGS......Page 314
CALIBRATION......Page 316
SPARES HOLDING......Page 317
UPGRADES, BUG FIXES, AND PATCHES......Page 318
BUG FIXES AND PATCHES......Page 319
UPGRADE CONSIDERATIONS......Page 320
AVAILABILITY OF SOFTWARE AND REFERENCE DOCUMENTATION......Page 321
RECENT INSPECTION FINDINGS......Page 322
DATA LIFE CYCLE......Page 323
RECENT INSPECTION FINDINGS......Page 324
BACKUPS AND RESTORATION......Page 325
SCHEDULING......Page 326
ARCHIVING AND RETRIEVAL......Page 327
STORAGE REQUIREMENTS......Page 328
PROCEDURES AND PLANS......Page 329
REDUNDANT SYSTEMS AND COMMERCIAL HOT SITES......Page 330
SERVICE BUREAUS......Page 331
SOFTWARE LICENSES......Page 332
SECURITY......Page 333
MANAGEMENT......Page 334
COMPUTER VIRUSES......Page 335
RECENT INSPECTION FINDINGS......Page 336
CONTRACTS AND SERVICE LEVEL AGREEMENTS......Page 338
RECENT INSPECTION FINDINGS......Page 339
PERIODIC REVIEW......Page 340
REVALIDATION......Page 342
RECENT INSPECTION FINDINGS......Page 343
REFERENCES......Page 344
SITE CLOSURES, DIVESTMENTS AND ACQUISITIONS......Page 345
Systems Management......Page 346
Records Management......Page 348
RETIREMENT......Page 349
LONG-TERM PRESERVATION OF ARCHIVE RECORDS......Page 350
Maintain Legacy Computerized System......Page 352
Store Data in an Industry Standard Format......Page 353
REPLACEMENT SYSTEMS......Page 354
MIGRATION STRATEGY......Page 355
LEGACY SYSTEMS......Page 356
REFERENCES......Page 357
APPENDIX 13A: EXAMPLE RETIREMENT CHECKLIST......Page 358
CONTENTS......Page 359
QUALITY AND COMPLIANCE ROLES......Page 360
CONCEPT OF INTERNAL SUPPLIER......Page 361
Duty and Standard of Care......Page 362
Legal Defensive Positions......Page 363
REGULATORY REQUIREMENTS......Page 364
ORGANIZATIONAL CAPABILITY......Page 365
Records Management......Page 366
STANDARDIZING COMPUTER APPLICATIONS......Page 367
APPROACH TO STANDARDIZED SOFTWARE VALIDATION......Page 368
SOFTWARE REUSE......Page 370
ISOLATING GXP FUNCTIONALITY FOR VALIDATION......Page 371
SEPARATING COMPUTER NETWORK INFRASTRUCTURE......Page 372
SETTING PRIORITIES......Page 373
HAZARD CONTROL......Page 374
INTERIM MEASURES......Page 376
VALIDATION......Page 377
RECENT INSPECTION FINDINGS......Page 378
APPROACH TO PROJECTS......Page 379
APPROACH TO DATA......Page 380
REFERENCES......Page 381
APPENDIX 14A: ERROR RATE TABLES......Page 383
CONTENTS......Page 385
ELECTRONIC RECORDS......Page 386
RECORD LIFE CYCLE......Page 387
AUDIT TRAILS......Page 389
COPIES OF RECORDS......Page 390
RECENT INSPECTION FINDINGS......Page 391
ELECTRONIC SIGNATURES......Page 392
SIGNATURE ATTRIBUTES......Page 393
Passwords......Page 394
RECENT INSPECTION FINDINGS......Page 395
SEQUENCE CHECKS......Page 396
RECENT INSPECTION FINDINGS......Page 397
BACKUPS AND ARCHIVES......Page 398
BUSINESS CONTINUITY PLANNING......Page 399
RECENT INSPECTION FINDINGS......Page 400
HAZARD STUDY......Page 401
REGULATORY EXPECTATIONS......Page 402
MASTER PLANS......Page 403
INSPECTION ANALYSIS......Page 404
REFERENCES......Page 406
SUMMARY OF REFERENCES IN GMP......Page 407
SUMMARY OF REFERENCES IN GDP......Page 408
SUMMARY OF REFERENCES IN GMP......Page 409
SUMMARY OF REFERENCES IN GDP......Page 410
CONTENTS......Page 411
INSPECTION PRACTICE......Page 412
APPROACH TO ORGANIZATIONAL CAPABILITY......Page 413
APPROACH TO INDIVIDUAL COMPUTER SYSTEMS......Page 414
RECEIVING AN INSPECTION REQUEST......Page 416
PREPARING FOR AN INSPECTION......Page 417
HOSPITALITY......Page 418
CONDUCTING THE INSPECTION......Page 419
AFTER THE INSPECTION......Page 421
GLOBAL COMMITMENTS......Page 422
ISO 9000 AND VALIDATION......Page 423
SYSTEM/PROJECT OVERVIEWS......Page 424
DOCUMENTATION......Page 425
TRAINED PERSONNEL......Page 426
KNOWLEDGE MANAGEMENT......Page 427
DIRECT ACCESS TO ELECTRONIC INFORMATION BY REGULATORS......Page 428
INSPECTION ANALYSIS......Page 429
POTENTIAL CAUSES OF VALIDATION FAILURE......Page 430
REFERENCES......Page 431
APPENDIX 16A: PREINSPECTION QUESTIONNAIRE......Page 433
APPENDIX 16B: GLP INSPECTION CHECKLIST......Page 434
APPENDIX 16C: GMP INSPECTION CHECKLIST......Page 435
APPENDIX 16D: ELECTRONIC RECORD/SIGNATURE INSPECTION CHECKLIST......Page 438
APPENDIX 16E: RECENT FDA WARNING LETTERS......Page 439
CONTENTS......Page 443
CAPABILITY APPRAISALS......Page 444
CAPABILITY CHARACTERISTICS......Page 445
SUPPLIER CAPABILITY ASSESSMENTS......Page 446
PROJECT VALIDATION METRICS......Page 447
DESIGN AND DEVELOPMENT METRICS......Page 448
TESTING METRICS......Page 449
UNDERSTANDING CONTRIBUTORY FACTORS......Page 450
RULES OF THUMB......Page 451
OPERATION AND MAINTENANCE METRICS......Page 452
CORRECTIVE MAINTENANCE METRICS......Page 453
DEPENDABILITY METRICS......Page 454
LEAN VALIDATION......Page 455
Realize Benefits......Page 456
SIX SIGMA VALIDATION......Page 458
BEST PRACTICE EXPECTATIONS......Page 460
REFERENCES......Page 462
Level 3 Questions......Page 463
Level 5 Questions......Page 464
APPENDIX 17B: REFERENCES FOR COST OF VALIDATION METRICS......Page 466
APPENDIX 17C: SIX SIGMA TOOL BOX......Page 467
COMPUTING ENVIRONMENT......Page 469
THE BUSINESS CASE FOR VALIDATION......Page 470
GOLDEN RULES REMAIN UNCHANGED......Page 471
ORGANIZATIONAL CHANGE......Page 472
REDUCING COSTS......Page 474
REFERENCES......Page 475
CONTENTS......Page 476
OVERVIEW OF VALIDATION STEPS ASSOCIATED WITH COMPUTER SYSTEMS......Page 478
USER REQUIREMENTS AND FUNCTIONAL SPECIFICATIONS......Page 479
RESPONSIBILITIES OF VENDORS AND USERS......Page 481
VALIDATION OF NEWLY PURCHASED SYSTEMS WITHOUT EVIDENCE OF VALIDATION FROM THE VENDOR......Page 482
VALIDATION OF USER-CONTRIBUTED SOFTWARE (E.G., MACROS)......Page 483
INSTALLATION......Page 484
OPERATIONAL QUALIFICATION AND ACCEPTANCE TESTING......Page 485
QUALIFICATION OF SOFTWARE......Page 486
PREVENTIVE MAINTENANCE......Page 487
SYSTEM SUITABILITY TESTS AND QUALITY CONTROL SAMPLE ANALYSIS FOR ONGOING PERFORMANCE QUALIFICATION......Page 488
CHANGE CONTROL......Page 489
REFERENCES......Page 490
CONTENTS......Page 492
METHOD FILES......Page 494
INTERPRETATION OF CHROMATOGRAPHIC DATA......Page 496
INSTRUMENT CONTROL......Page 498
ARCHITECTURE OF A NETWORKED CDS......Page 499
Gaines Chemical Company FDA 483 Observations......Page 500
Noramco FDA 483 Observations......Page 501
Key Inspection Learning Points......Page 502
Mapping and Understanding the Current Process......Page 503
CDS Life Cycle......Page 505
Defining the Basic CDS Functions......Page 507
Documenting the System Requirements for Traceability......Page 509
VALIDATION PLAN......Page 510
Installation Qualification (IQ)......Page 511
Assess IQ and OQ Documentation......Page 512
PQ Test Plan and Test Scripts......Page 513
Write the Test Scripts......Page 514
ANALYTICAL RUN CAPACITY......Page 515
LOGICAL SECURITY AND ACCESS CONTROL......Page 516
PERSONNEL AND TRAINING RECORDS......Page 517
STANDARD OPERATING PROCEDURES (SOPS)......Page 518
MANUAL AND AUTOMATED TESTING......Page 519
Review Existing Documents......Page 520
MAINTAINING THE VALIDATION STATUS DURING OPERATIONAL LIFE......Page 521
Backup Log......Page 522
Software Error Logging and Resolution......Page 523
REVALIDATION CRITERIA......Page 524
Data Acquisition and Processing Software Applications......Page 525
DIFFERENCES BETWEEN THE NEW AND LEGACY CDS SYSTEMS......Page 526
Step 2: Carrying Out a Risk Assessment......Page 527
Supplier-Supplied Data Conversion Utilities......Page 529
Evolution of the Data Migration Design......Page 530
Retention Time......Page 531
Integration Algorithms and Calculated Results......Page 532
CDS SYSTEM RETIREMENT......Page 534
REFERENCES......Page 536
CONTENTS......Page 538
FUNCTIONALITY......Page 541
THE REGULATORY INFLUENCE......Page 542
THE GOOD PRACTICE APPROACH TO LIMS VALIDATION......Page 543
SUPPLIER AND APPLICATION SELECTION......Page 545
VALIDATION PLANNING......Page 547
User Requirements Specification......Page 548
Design Specifications......Page 550
Design Review......Page 551
APPLICATION DEVELOPMENT......Page 552
Configuration Management......Page 554
Source Code Review......Page 555
Prequalification Activities......Page 556
Installation Qualification......Page 557
Operational Qualification......Page 558
Operational Qualification Protocol......Page 559
Operational Qualification Report......Page 560
LIMS VALIDATION REPORT......Page 561
CHANGE CONTROL......Page 562
Software Bug Fixes and Updates to Core LIMS......Page 563
LIMS SECURITY......Page 564
CONCLUSION......Page 565
REFERENCES......Page 566
CONTENTS......Page 567
GENERAL VALIDATION REQUIREMENTS......Page 568
Subject Information Systems......Page 570
Optical Character Recognition (OCR)......Page 571
Data Management Systems......Page 572
Randomization Systems......Page 573
Statistical Analysis Systems......Page 574
Electronic Transfer of Data and Software......Page 575
Protocol Management......Page 576
Regulatory Submission and Electronic Publishing Systems......Page 577
Training Record Systems......Page 578
ELECTRONIC RECORDS AND ELECTRONIC SIGNATURES......Page 579
OTHER INTERNATIONAL REGULATORY REQUIREMENTS......Page 580
REGULATORY INSPECTION......Page 581
REFERENCES......Page 582
CONTENTS......Page 583
INSTRUMENT APPLICATION DESIGN......Page 585
FACTORY CALIBRATION......Page 586
Hazardous Area Approval Certificates......Page 587
EQUIPMENT DELIVERY, INSPECTION, PROTECTION, AND STORAGE......Page 588
TEST STATUS INDICATION......Page 589
SITE CALIBRATION......Page 590
LOOP TESTING......Page 591
Loop Testing Procedure......Page 592
INSTALLATION QUALIFICATION......Page 593
TESTING......Page 594
EMERGENCY SHUTDOWN SYSTEMS......Page 595
ANALYZER PACKAGES......Page 596
RETROSPECTIVE VALIDATION......Page 597
REFERENCES......Page 598
APPENDIX 23A: THE INSTRUMENT APPLICATION DEVELOPMENT LIFE CYCLE......Page 600
APPENDIX 23B: OVERVIEW OF THE INSTRUMENT APPLICATION DESIGN PROCESS......Page 601
APPENDIX 23C: SAMPLE INSTRUMENT PREINSTALLATION CALIBRATION SHEET......Page 602
APPENDIX 23D: SAMPLE INSTRUMENT LOOP CHECK SHEET......Page 603
INSTRUMENT SCHEDULE......Page 604
INSTRUMENT SPECIFICATION/DATA SHEETS......Page 605
PNEUMATIC TUBING SCHEDULES......Page 606
FIELD PANEL SPECIFICATION AND DRAWINGS......Page 607
ELECTRICAL HOOKUP (LOOP OR WIRING DIAGRAMS) DRAWINGS......Page 608
EARTHING SCHEDULES AND DRAWINGS......Page 609
INSTRUMENT INSTALLATION SPECIFICATION......Page 610
ELECTRICAL AND INSTRUMENTATION INTERFACE PANEL......Page 611
SPECIAL INSTRUMENT SYSTEMS......Page 612
CONTENTS......Page 613
VALIDATION OF AUTOMATED SYSTEMS......Page 614
VALIDATION OF A PLC-BASED SYSTEM......Page 615
THE VALIDATION PROCESS......Page 616
PLANNING......Page 617
SPECIFICATION......Page 618
COMPUTER HAZARD AND OPERABILITY STUDY (CHAZOP)......Page 620
TESTING......Page 621
VALIDATION OF LEGACY PLC-BASED SYSTEMS......Page 624
PLCs AS PART OF A SYSTEM......Page 625
ELECTRONIC RECORD/ELECTRONIC SIGNATURE (ERES) CONSIDERATIONS......Page 626
REFERENCES......Page 627
CONTENTS......Page 629
VALIDATION OF IPCS......Page 630
VALIDATION LIFE CYCLE......Page 631
SUPPLIER AUDIT......Page 633
FUNCTIONAL DESIGN SPECIFICATION......Page 634
SOFTWARE DESIGN......Page 635
DESIGN REVIEW......Page 637
SUPPLIER TESTING......Page 638
OPERATIONAL QUALIFICATION (OQ)......Page 639
DATA MIGRATION AND CUTOVER MANAGEMENT......Page 640
ONGOING SUPPORT......Page 641
MAINTAINING THE VALIDATED STATUS OF THE IPC......Page 642
IPC SECURITY......Page 643
REFERENCES......Page 644
CONTENTS......Page 645
VALIDATION LIFE CYCLE......Page 646
VALIDATION PLANNING......Page 647
PROJECT PLAN......Page 650
RISK MITIGATION......Page 651
QUALITY ASSURANCE......Page 652
SYSTEM SPECIFICATION......Page 653
APPLICATION SOFTWARE......Page 654
SYSTEM TESTING......Page 656
SYSTEM ACCEPTANCE......Page 658
LAYERS OF SECURITY......Page 659
PHYSICAL SECURITY......Page 660
PROCEDURAL SECURITY......Page 661
LOGICAL SECURITY......Page 662
ELECTRONIC RECORDS AND ELECTRONIC SIGNATURES......Page 663
MANUFACTURING EXECUTION SYSTEMS......Page 665
REFERENCES......Page 667
OVERVIEW OF A DISTRIBUTED CONTROL SYSTEM (DCS)......Page 668
INTRODUCTION TO S88.01......Page 669
USER REQUIREMENTS......Page 671
VALIDATION APPROACH......Page 673
SYSTEM CONFIGURATION......Page 674
TRAINING......Page 676
PREDELIVERY TESTING......Page 677
OPERATIONAL QUALIFICATION (OQ)......Page 678
OPERATION AND MAINTENANCE......Page 679
ACKNOWLEDGMENTS......Page 680
REFERENCES......Page 681
CONTENTS......Page 682
PROJECT OBJECTIVES......Page 683
VALIDATION......Page 684
General Requirements......Page 685
RISK ASSESSMENT......Page 686
Test Strategy......Page 687
Special Testing......Page 688
ONGOING EVALUATION......Page 689
High Degree of Automation Required......Page 691
REFERENCES......Page 692
RISK ASSESSMENT......Page 693
SUPPLIER SELECTION RISK ASSESSMENT......Page 694
THE GAMP CATEGORIES......Page 696
CLASSIFICATION OF HARDWARE......Page 697
FUNCTION RISK ASSESSMENT......Page 699
COMBINING RISK ASSESSMENT INFORMATION INTO A VALIDATION STRATEGY......Page 701
REFERENCES......Page 702
CONTENTS......Page 703
RECENT INSPECTION FINDINGS......Page 704
NONASEPTIC MANUFACTURING BMS......Page 706
RISK ASSESSMENT......Page 707
Component Criticality Assessment......Page 708
Component Criticality vs. System Impact......Page 709
Independent Monitoring......Page 710
GOOD ENGINEERING PRACTICE (GEP)......Page 711
SUPPLIER AUDIT......Page 712
SYSTEM SPECIFICATIONS......Page 714
ON-SITE TESTING......Page 715
BENEFITS DELIVERY......Page 716
REFERENCES......Page 717
CONTENTS......Page 718
MAP PROCESSES......Page 719
System Concept......Page 721
Systems and Functional Performance Criteria......Page 722
OPERATION AND MAINTENANCE......Page 725
DEFINING INFORMATION NEEDS TO SUPPORT THE ENGINEERING STRATEGY......Page 726
ELECTRONIC RECORDS AND ELECTRONIC SIGNATURES......Page 728
PHYSICAL ARCHITECTURE OF THE EMS......Page 729
System Control and Performance Monitoring......Page 730
TECHNICAL ISSUES......Page 731
PRINCIPLES OF CRITICALITY-BASED VALIDATION......Page 732
VALIDATION LIFE CYCLE......Page 733
SUPPLIER AUDIT......Page 734
FUNCTIONAL DESIGN SPECIFICATION (FDS)......Page 739
HARDWARE DESIGN SPECIFICATION (HDS)......Page 741
GOOD PROGRAMMING PRACTICE AND SOURCE CODE REVIEWS (SCR)......Page 742
Application Configuration Specification......Page 743
SUPPLIER TESTING......Page 744
OPERATIONAL QUALIFICATION (OQ)......Page 745
VALIDATION REPORT......Page 748
REFERENCES......Page 749
CONTENTS......Page 751
WINDOWS APPLICATIONS......Page 752
GENERAL REQUIREMENTS FOR THE VALIDATION......Page 755
Print Headings on Every Page without Macros......Page 756
Procedure for Class 3 Spreadsheets......Page 757
Procedure for Class 5 Spreadsheets......Page 759
PROTECTION OF WORKBOOKS......Page 760
EXAMPLE REGULATORY OBSERVATIONS......Page 761
REFERENCES......Page 766
APPENDIX 32A: PROCESS TO ENABLE SPREADSHEET AUDIT TRAILS......Page 767
CONTENTS......Page 771
RECORDS AND FIELDS......Page 772
TYPES OF DATABASE......Page 773
USER REQUIREMENTS......Page 774
FUNCTIONAL SPECIFICATIONS......Page 775
Field Definition......Page 776
Audit Trails......Page 777
Test Planning......Page 778
Qualification......Page 779
TRACEABILITY......Page 780
BACKUP/RECOVERY......Page 781
CHANGE CONTROL......Page 782
DECOMMISSIONING......Page 783
ACKNOWLEDGMENTS......Page 784
REFERENCES......Page 785
CONTENTS......Page 786
THE REGULATORY ENVIRONMENT......Page 787
IMPLEMENTATION AND VALIDATION OF AN EDMS......Page 788
PROJECT TEAM......Page 789
SELECTION OF A SUPPLIER AND SYSTEM INTEGRATOR......Page 791
FUNCTIONAL SPECIFICATION (FS)......Page 792
SYSTEM BUILD......Page 793
INSTALLATION QUALIFICATION (IQ)......Page 794
OPERATIONAL QUALIFICATION (OQ)......Page 795
DATABASE POPULATION......Page 796
VALIDATION REPORT......Page 797
MAINTAINING THE VALIDATED STATE......Page 798
REFERENCES......Page 799
MISSION IMPOSSIBLE?......Page 800
PROJECT APPROACH......Page 801
MAINTAINING OPERATIONAL COMPLIANCE......Page 808
ELECTRONIC RECORDS AND ELECTRONIC SIGNATURES......Page 810
INSPECTION CASE HISTORY......Page 811
CONCLUDING REMARKS......Page 813
REFERENCES......Page 814
APPENDIX 35A: EXAMPLE PROCUREMENT BUSINESS PROCESSES WITH SOPs......Page 815
APPENDIX 35B: EXAMPLE PRODUCTION PLANNING BUSINESS PROCESSES WITH SOPs......Page 816
APPENDIX 35C: EXAMPLE MANUFACTURING BUSINESS PROCESSES WITH SOPs......Page 817
APPENDIX 35D: EXAMPLE SALES AND DISTRIBUTION BUSINESS PROCESSES WITH SOPs......Page 818
APPENDIX 35E: EXAMPLE FINANCE BUSINESS PROCESSES WITH SOPs......Page 819
APPENDIX 35F: EXAMPLE MRP II GXP IMPACTING FUNCTIONALITY......Page 820
APPENDIX 35G: EXAMPLE MRP II VALIDATION DOCUMENT SET......Page 821
CONTENTS......Page 822
MARKETING APPLICATIONS......Page 824
SUPPLY APPLICATIONS......Page 826
REGULATORY REQUIREMENTS......Page 828
REQUIREMENT TO FOLLOW STANDARD OPERATING PROCEDURES AND QUALITY STANDARDS......Page 829
VALIDATION DETERMINATION......Page 830
VALIDATION PLAN......Page 831
USER REQUIREMENTS SPECIFICATION......Page 832
IDENTIFICATION AND SEGREGATION OF GXP AND NON-GXP DATA......Page 833
DEVELOPMENT TESTING......Page 834
USER QUALIFICATION......Page 835
USER DOCUMENTATION......Page 836
TRAINING......Page 837
Emergency Changes......Page 838
BACKUPS......Page 839
DECOMMISSIONING......Page 840
DATA ARCHIVING AND RECORD RETENTION......Page 841
STORAGE CONDITIONS......Page 842
OUT OF SPECIFICATION (OOS)......Page 843
PRODUCT RECALL......Page 844
APPLICATIONS STORING GXP DATA IN MULTIPLE LANGUAGES......Page 845
OUTSOURCING ACTIVITIES TO THIRD PARTIES......Page 846
INTERNET APPLICATIONS......Page 847
USE OF SPREADSHEETS......Page 848
AWARENESS OF RELEVANT REGULATORY EXPECTATIONS......Page 849
RELIANCE ON SUPPLIERS......Page 850
USE OF ELECTRONIC RECORDS AND ELECTRONIC SIGNATURES......Page 851
CONCLUSION......Page 852
REFERENCES......Page 853
APPENDIX 36A: POSSIBLE GXP BUSINESS PROCESSES SUPPORTED BY MARKETING AND SUPPLY APPLICATIONS......Page 855
APPENDIX 36B: EXAMPLES OF REGULATORY DATA TYPES WITHIN MARKETING AND SUPPLY BUSINESS PROCESSES......Page 857
CONTENTS......Page 862
SETTING PRIORITIES......Page 864
CLIENT ENVIRONMENT......Page 865
NETWORKS......Page 866
DOCUMENTATION AND INFORMATION MANAGEMENT......Page 867
ESTABLISHING BASIC CONTROLS AND DOCUMENTATION......Page 868
QUALITY MANUAL OR QUALITY PLAN......Page 869
PLANNING......Page 870
TECHNICAL SPECIFICATION......Page 871
OPERATIONAL PROCEDURES......Page 872
NETWORKS......Page 873
CLIENT (DESKTOP AND LAPTOPS)......Page 874
ELECTRONIC RECORDS AND ELECTRONIC SIGNATURES......Page 875
INTRANET, INTERNET, AND EXTRANET ISSUES......Page 876
INTERNET DATA ENTRY......Page 880
ENTERPRISE USER DIRECTORY......Page 881
OUTSOURCING......Page 882
DUE DILIGENCE PROCESS......Page 883
THE CONTRACT......Page 884
CULTURAL CHANGES......Page 885
ROLE OF THE SUPPLIER......Page 886
REFERENCES......Page 887
APPENDIX 37A: BASELINE QUALITY ASSESSMENT......Page 888
APPENDIX 37B: ELECTRONIC RECORDS AND ELECTRONIC SIGNATURE INFRASTRUCTURE CHALLENGES......Page 893
CONTENTS......Page 895
A SITE MES APPLICATION (MANUFACTURING EXECUTION SYSTEM)......Page 896
NETWORK COMPONENTS......Page 898
THICKWIRE......Page 900
FIBER OPTIC......Page 901
REPEATERS......Page 902
Bridges and Routers......Page 903
REGULATORY REQUIREMENTS FOR THE NETWORKS......Page 904
EXAMPLES OF NETWORK INSPECTION FINDINGS......Page 905
VALIDATION STRATEGY FOR THE NETWORKS......Page 906
VALIDATION AND SYSTEM LIFE CYCLE......Page 907
SPECIFICATIONS OF NETWORKS......Page 910
LAN Architecture Section......Page 911
PRODUCTION OF A WIDE AREA NETWORK DESIGN SPECIFICATION......Page 912
Network Management Section......Page 913
Scope Section......Page 914
PRACTICAL ISSUES......Page 915
REFERENCES......Page 916
CONTENTS......Page 917
OPEN VS. CLOSED SYSTEMS......Page 919
DATA TRANSFER THROUGH THE INTERNET......Page 920
HASH FUNCTIONS TO ENSURE DATA INTEGRITY......Page 921
E-MAILS THROUGH S/MIME......Page 922
VIRTUAL PRIVATE NETWORKS......Page 923
CONFIGURATION MANAGEMENT......Page 924
TESTING BROWSER FUNCTIONALITY AND USER INTERFACE......Page 925
SECURITY TESTING......Page 926
DEVELOPMENT AND COMMUNICATION OF PROCEDURES......Page 927
REFERENCES......Page 928
CONTENTS......Page 929
REQUIREMENTS......Page 931
RISK ASSESSMENT (SAFETY CASE)......Page 933
DESIGN......Page 934
DESIGN REVIEW......Page 935
ASSEMBLY......Page 936
REPORTING......Page 937
INSPECTION FINDINGS......Page 939
REFERENCES......Page 941
CONTENTS......Page 943
MEETING REGULATORY EXPECTATIONS......Page 944
REGULATORY REPORTING REQUIREMENTS......Page 945
A STRUCTURED LIFE-CYCLE APPROACH......Page 946
SYSTEM VALIDATION PROTOCOLS......Page 947
CHANGE MANAGEMENT......Page 948
COMPUTER SYSTEM ENVIRONMENTS......Page 949
Validation Documentation......Page 950
TRAINING......Page 951
System Administrator......Page 952
REFERENCES......Page 953
FOUNDING PRINCIPLES......Page 955
TOPOLOGY......Page 956
USER REPORTING......Page 957
PROCESS VALIDATION......Page 958
REFERENCES......Page 959
Glossary......Page 960
REFERENCE WEBSITES......Page 969