Data Integrity and Data Governance: Practical Implementation in Regulated Laboratories

Cover......Page 1
Data Integrity and Data Governance: Practical Implementation in Regulated Laboratories......Page 2
Preface......Page 6
Acknowledgements......Page 8
Glossary, Abbreviations and Data Integrity Terms......Page 10
Contents......Page 34
1.1 Aims and Objectives......Page 63
1.2.2 You Do Not Read the Regulations!......Page 64
1.2.4 Data Governance......Page 66
1.2.5 Data Integrity......Page 68
1.2.6 Quality Oversight for Data Integrity......Page 70
1.4.1 Integration Within the Pharmaceutical Quality System......Page 71
1.4.4 The European Equivalent of cGMP......Page 73
1.5.2 What Do These Definitions Mean......Page 74
1.5.3 ALCOA+ Criteria for Integrity of Laboratory Data......Page 75
1.6.1 From Sample to Reportable Result......Page 77
1.6.2 Contextual Metadata and a Reportable Result......Page 78
1.6.3 Data Integrity – Can I Trust the Data......Page 80
1.6.5 The Proposed FDA GLP Quality System......Page 82
1.7 Static Versus Dynamic Data......Page 83
1.8.1 Data Integrity Is More than Just Numbers......Page 84
1.8.3 Data Integrity Is Not Just 21 CFR 11 or Annex 11 Compliance......Page 85
1.9 It’s Déjà vu all Over Again!......Page 86
References......Page 87
2.1 Barr Laboratories 1993: You Cannot Test into Compliance......Page 90
2.1.2 Key Laboratory Findings from the Judgement......Page 91
2.2.2 483 Observations......Page 92
2.2.3 Regulatory Response......Page 93
2.3.2 Details of the 2012 Consent Decree......Page 94
2.4 Court Case for GLP Data Falsification......Page 95
2.6 The Cost of Data Integrity Non-compliance......Page 96
2.6.1 Relative Costs of Compliance Versus Non-compliance......Page 97
2.7.1 Why Use Only FDA Warning Letters and 483 Observations......Page 98
2.7.2 Quality Management System Failures......Page 99
2.7.3 Instrument Citations......Page 101
2.7.5 Failure to Have Complete Laboratory Records......Page 103
2.7.7 Industrial Scale Shredding and Discarding of GMP Documents......Page 105
References......Page 106
3.1.1 EU Good Manufacturing Practice Chapter 1......Page 109
3.1.3 21 CFR 211 cGMP Regulations for Finished Pharmaceutical Goods......Page 110
3.2.1 Background to the Proposed Regulation......Page 112
3.2.2 New Data Quality and Integrity Requirements......Page 113
3.2.5 No Hiding Place for GLP Data Integrity Issues......Page 114
3.3 Overview of Regulatory Guidance Documents for Data Integrity......Page 115
3.4.1 FDA Guide to Inspection of Pharmaceutical Quality Control Laboratories......Page 117
3.4.2 FDA Compliance Program Guide 7346.832 on Pre Approval Inspections......Page 118
3.4.3 FDA Level 2 Guidance......Page 119
3.4.5 FDA Guidance on Data Integrity and Compliance with cGMP......Page 120
3.5.1 Initial Request to Industry December 2013......Page 122
3.5.3 MHRA GXP Data Integrity Guidance for Industry......Page 123
3.5.4 MHRA Definition of Raw Data......Page 124
3.6 PIC/S Guidance Documents......Page 125
3.7 WHO Guidance on Good Data and Records Management Practices......Page 126
3.8 GAMP Guide for Records and Data Integrity......Page 127
3.9 PDA Technical Report 80......Page 130
3.9.2 Data Integrity in Microbiology Laboratories......Page 132
3.9.3 Data Integrity in Analytical QC Laboratories......Page 133
3.10.2 In the Beginning …......Page 134
3.10.4 The GLP Quality System – The Proposed 21 CFR 58 Update......Page 136
3.10.5 Extracting Principles for Laboratory GXP Raw Data......Page 137
3.10.6 Visualising What Raw Data Mean......Page 138
3.11 Regulations and Data Integrity Guidance Summary......Page 140
References......Page 141
4.1.1 EU GMP Chapter 1 Pharmaceutical Quality System......Page 144
4.1.2 FDA Proposed GLP Quality System Update......Page 145
4.1.3 MHRA GXP Data Integrity Guidance......Page 146
4.1.4 WHO Guidance on Good Records and Data Management Practices......Page 147
4.1.5 PIC/S PI-041 – Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments......Page 149
4.2 The Rationale for Data Governance: Regulatory Boot or Business Imperative......Page 150
4.3 Perspectives of Data Governance Outside the Pharmaceutical Industry......Page 151
4.4.1 Summary of Regulatory Guidance for Data Governance......Page 152
4.4.2 Main Data Governance Areas......Page 154
4.4.3 Further Data Governance Chapters in this Book......Page 155
References......Page 156
5.1 A Data Integrity Model......Page 158
5.1.2 Descriptions of the Four Levels in the Model......Page 159
5.1.3 An Analogy of Building a House......Page 161
5.1.4 Focus on the Laboratory Levels of the Data Integrity Model......Page 162
5.2.2 Data Governance Functions in the Foundation Level......Page 163
5.3.1 Analytical Instrument Qualification and Computerised System Validation (AIQ and CSV)......Page 166
5.4.1 Validation of Analytical Procedures......Page 167
5.4.4 Manual Analytical Procedures Must Be Designed for Data Integrity......Page 168
5.6.1 Quality Oversight of Laboratory Procedures and Work......Page 169
5.7.1 The Data Integrity Model in Practice......Page 170
5.8 Mapping the WHO Guidance to the Data Integrity Model......Page 172
5.9.1 Data Management Maturity Model......Page 174
5.9.2 Data Integrity Maturity Model......Page 177
References......Page 179
6.1.1 ICH Q10 Pharmaceutical Quality Systems......Page 181
6.1.2 EU GMP Chapter 1......Page 182
6.1.3 PIC/S-041 Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments......Page 183
6.1.4 WHO Guidance on Good Data and Record Management Practices......Page 184
6.1.5 Update of the US GLP Regulations......Page 185
6.1.7 A Summary of Regulatory and Industry Guidance Documents......Page 186
6.2 Data Governance Roles and Responsibilities – Corporate Level......Page 187
6.4 Management, Monitoring and Metrics......Page 191
6.5.1 From Data Governance to Data Ownership......Page 193
6.5.3 Can a Process Owner Be a Data Owner......Page 194
6.5.4 Other Data Governance Roles at the System Level......Page 195
6.5.5 Data Owner......Page 197
6.5.7 Is a Lab Administrator a Data Steward......Page 198
6.6.1 Where Are We Now......Page 199
6.6.2 The Hybrid System Nightmare......Page 200
References......Page 202
7.1.1 EU GMP Chapter 4 on Documentation......Page 204
7.1.2 WHO Guidance on Good Data and Record Management Practices......Page 205
7.1.4 Regulatory Requirements Summary......Page 206
7.2.1 Background to EPA and Data Integrity......Page 207
7.2.3 NELAC Quality System......Page 208
7.2.4 NELAC Data Integrity Training......Page 209
7.3 Corporate Data Integrity Policy Coupled with Effective Training......Page 211
7.3.1 Contents of a Corporate Data Integrity Policy......Page 213
7.3.2 Training in the Data Integrity Policy......Page 214
7.5 Principles of Good Documentation Practice......Page 217
7.5.1 Say What You Do......Page 218
7.5.4 Automating Procedure Execution......Page 219
7.6.1 Principles for GXP Laboratory Raw Data and Complete Data......Page 220
7.6.3 Example 1 – Paper Records from a Manual Test......Page 221
7.6.4 Example 2 – Spectroscopic Analysis Using a Hybrid System......Page 223
7.6.5 Example 3 – Chromatographic Analysis with a CDS Interfaced with a LIMS......Page 225
7.7 Good Documentation Practice for Paper Records......Page 227
7.7.1 Recording Observations and Results......Page 228
7.7.2 Examples of Good and Poor Documentation Practice for Handwritten Records......Page 229
7.7.3 Fat Finger, Falsification and Fraud – Take 1......Page 230
7.8 Good Documentation Practice for Hybrid Records......Page 231
7.8.1 Record Signature Linking for Hybrid Systems – Spreadsheet Example......Page 233
7.9 Good Documentation Practice for Electronic Records......Page 234
7.11 Role of the Instrument Log Book......Page 235
7.11.1 EU GMP Chapter 4 on Documentation......Page 237
7.11.4 FDA Inspection of Pharmaceutical QC Laboratories......Page 239
7.12.1 Data Integrity Training for a Chromatography Data System: Operational SOPs......Page 240
References......Page 241
8.1.1 WHO Guidance on Good Data and Record Management Practices......Page 243
8.1.2 PIC/S PI-041 Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments......Page 244
8.1.4 Regulatory Guidance Summary......Page 245
8.2.1 Cressey's Fraud Triangle......Page 246
8.2.2 Breaking the Fraud Triangle......Page 247
8.2.3 Managerial and Peer Pressures Can Influence Analytical Results......Page 248
8.3 ISPE Cultural Excellence Report......Page 249
8.4.2 Talk the Talk and Walk the Walk......Page 250
8.5 Mind Set and Attitudes......Page 251
8.5.3 How Do I Raise Problems to Management......Page 252
8.6.1 Where Does a Gemba Walk Fit in a QMS......Page 254
8.6.2 What Gemba Walks Are and Are Not......Page 255
8.6.4 Activation Energy for a Gemba Walk......Page 256
8.6.5 Performing the Gemba Walk......Page 257
8.6.7 Generic Questions for a Gemba Walk......Page 258
8.7.1 To Err Is Human......Page 259
8.7.3 What Is the Fat Finger Rate in a Laboratory......Page 260
8.7.4 Learning from Health Service Studies......Page 261
References......Page 262
9.1.1 MHRA GXP Data Integrity Guidance......Page 264
9.1.3 PIC/S PI-041 Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments......Page 265
9.1.4 Regulatory Requirements Summary......Page 266
9.2.1 GAMP Guide on Records and Data Integrity......Page 267
9.2.2 Validation of Chromatography Data Systems......Page 268
9.2.3 Critique of the Two Life Cycle Models......Page 269
9.3.1 Overview of an Analytical Data Life Cycle......Page 270
9.3.2 Controlling the Analytical Data Life Cycle......Page 271
9.3.3 Phases of the Analytical Data Life Cycle......Page 272
9.3.5 The Requirement for Flexibility to Adapt to Different Analytical Procedures......Page 274
9.4.1 Spectrum of Analytical Instruments and Laboratory Computerised Systems......Page 277
9.5.1 PIC/S PI-041 Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments......Page 280
9.5.2 Initial Assessment of Risk of the Analytical Data Life Cycle Phases......Page 281
9.5.3 Phases of the Data Life Cycle are Equal but Some are More Equal than Others......Page 282
References......Page 283
Chapter 10 - Assessment and Remediation of Laboratory Processes and Systems......Page 285
10.1.3 MHRA GXP Data Integrity Guidance and Definitions......Page 286
10.2.2 Ensure Regulatory Compliance......Page 287
10.3.1 The Rationale for Current Approaches......Page 288
10.3.2 Assessment of Validated Computerised Systems......Page 289
10.4.2 What is Data Process Mapping......Page 291
10.4.3 Instrument Data System with Spreadsheet Calculations......Page 294
10.4.4 Spreadsheets Used for GMP Calculations Are High Risk......Page 295
10.4.5 Critical Activities in a Process......Page 296
10.4.6 Fix and Forget versus Delivering Business Benefits......Page 297
10.4.7 Short Term Remediation Leading to Long Term Solution......Page 298
10.5.2 A Risk Based Approach to Analysis by Observation......Page 300
10.6 Data Integrity Issues with Paper Records......Page 301
10.6.1 Blank Forms Must be Controlled with Accountability......Page 302
References......Page 303
11.1.1 Focus on the Key Data Integrity Issues with Paper Records......Page 304
11.1.4 MHRA Draft GXP Data Integrity Guidance......Page 305
11.1.7 FDA Data Integrity and Compliance with cGMP......Page 306
11.1.8 PIC/S PI-041 Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments......Page 307
11.1.10 Regulatory Guidance Summary......Page 308
11.2.1 Understanding Master Templates and Blank Forms......Page 309
11.2.3 Process for Generation, Review and Approval of a Master Template......Page 310
11.2.4 Requirements for the Issue and Reconciliation of Blank Forms......Page 313
11.2.5 Process for Issue and Reconciliation of Blank Forms......Page 315
11.2.6 Process for Issue and Reconciliation of Blank Forms......Page 316
11.3.2 FDA GMP 21 CFR 211......Page 317
11.3.5 Summary of Regulatory Requirements for an Instrument Log Book......Page 319
11.4.1 Why is an Instrument Log Book Important......Page 320
11.4.2 What Needs to be Entered in the Log Book......Page 321
11.4.3 Inspectors Know the Importance of an Instrument Log......Page 322
11.4.5 Instrument Log Books in Practice......Page 323
11.5.1 Is an Instrument Performing OK......Page 324
11.6.1 Automating Master Templates and Blank Forms......Page 325
11.6.2 Instrument Log Book......Page 326
References......Page 327
12.1.1 Electronic Records and Electronic Signatures Regulations (21 CFR 11)......Page 329
12.1.2 WHO Guidance on Good Data and Record Management Practices......Page 330
12.1.5 FDA Guidance for Industry Data Integrity and cGMP Compliance......Page 331
12.1.6 FDA Level 2 Guidance for Records and Reports......Page 333
12.2.1 WHO Definition of a Hybrid System......Page 334
12.3.1 A Typical Hybrid System Configuration......Page 335
12.3.2 File Organisation and Printing Results......Page 337
12.3.3 Synchronising Paper Printouts and Electronic Records......Page 338
12.4 Eliminate Hybrid Systems......Page 340
References......Page 342
13.1.1 WHO Guidance on Good Data and Record Management Practices......Page 343
13.1.2 PIC/S PI-041 Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments......Page 344
13.1.4 Regulatory Summary......Page 345
13.2.2 Back to the Future 2: Understanding the Current in cGMP......Page 346
13.2.3 The Pharmaceutical Industry is a Two Sigma Industry......Page 347
13.2.4 Are the Regulations Part of the Data Integrity Problem......Page 348
13.3 Design Principles for Electronic Working......Page 349
13.4 Designing Data Workflows 1 – Analytical Balances......Page 351
13.4.2 Recording a Weight by Observation......Page 352
13.4.3 Recording Balance Weights with a Printer......Page 353
13.4.4 Connecting the Balance to an Instrument Data System......Page 354
13.5.1 Options for Interfacing......Page 357
13.5.3 Unidirectional Interfacing from CDS to LIMS......Page 359
13.5.4 Bidirectional Interfacing Between CDS and LIMS......Page 361
13.6.1 Ensuring Data Integrity with Electronic Working......Page 363
References......Page 364
Chapter 14 - Data Integrity Centric Analytical Instrument Qualification and Computerised System Validation......Page 367
14.1.3 United States Pharmacopoeia ၘ on Analytical Instrument Qualification......Page 368
14.1.6 WHO Guidance on Good Data and Record Management Practices......Page 369
14.1.8 Regulatory Summary......Page 370
14.2.1 Relationship Between GMP and the Pharmacopoeias......Page 371
14.2.2 Importance of USP ၘ......Page 372
14.3.1 Data Quality Triangle......Page 373
14.4.1 Problems with the 2008 Version......Page 374
14.4.2 Revision Path of USP ၘ......Page 375
14.5.2 Omitted Sections in the New Version......Page 376
14.5.5 An Updated 4Qs Model......Page 377
14.5.6 Harmonisation of Qualification Approaches......Page 381
14.6.1 Role of the URS......Page 382
14.6.3 A Role of the Supplier: Write Meaningful Specifications......Page 383
14.6.4 How Minimal Is Minimal......Page 384
14.6.7 It's all About Investment Protection......Page 385
14.7 Software Validation Changes to USP ၘ......Page 386
14.7.1 Improving the Analytical Process......Page 387
14.7.2 A Validated System with Vulnerable Records Means Data Integrity Problems......Page 388
14.7.4 Brave New CSV World......Page 390
14.7.5 Turning Principles into Practice......Page 391
14.8 Performance Qualification......Page 393
14.8.1 Changes to USP ၘ and the Impact on Understanding of PQ......Page 394
14.8.2 Linking the URS, OQ, and PQ......Page 395
14.8.4 PQ for Group B Instruments......Page 396
14.8.5 PQ for Group C Instruments......Page 397
14.8.6 System Suitability Tests as Part of a PQ......Page 399
14.8.8 Holistic HPLC PQ Test......Page 400
References......Page 401
Chapter 15 - Validating Analytical Procedures......Page 404
15.1.4 Bioanalytical Method Validation Guidances......Page 405
15.1.6 Outsource Analytical Work with Care......Page 407
15.2.2 Business Rationale for Procedure Validation/Verification......Page 408
15.2.5 Update of ICH Q2(R1) to a Life Cycle Approach......Page 410
15.2.6 Pharmacopoeial Methods Do Not Work as Written......Page 411
15.3.1 Method Validation in the Data Integrity Model......Page 412
15.4.2 Bioanalytical Method Validation......Page 413
15.4.3 Validation Documentation for Analytical Procedures......Page 415
15.5.1 USP ሠ and Stimuli to the Revision Process......Page 416
15.5.2 Life Cycle of Analytical Procedures......Page 417
15.6.2 Advantages and Limitations of an Analytical Target Profile......Page 418
15.7.2 Information Gathering and Initial Procedure Design......Page 419
15.7.3 Iterative Method Development and Method Optimisation......Page 420
15.7.4 Risk Assessment and Management......Page 422
15.8.1 Planning the Validation......Page 423
15.8.2 Validation Report......Page 424
15.8.3 Analytical Procedure Transfer......Page 425
15.9.3 Validated Analytical Procedure......Page 426
References......Page 427
Chapter 16 - Performing an Analysis......Page 429
16.1.2 US GMP 21 CFR 211 GMP for Finished Pharmaceutical Products......Page 430
16.1.3 FDA Guide for Inspection of Pharmaceutical Quality Control Laboratories......Page 431
16.2.1 Linking the Data Integrity Model to the Analytical Process......Page 432
16.2.4 System Suitability Tests and Point of Use Checks......Page 434
16.3 The Scope of Analytical Procedures......Page 436
16.4.1 What the Regulators Want......Page 437
16.4.2 Sampling Is Critical......Page 438
16.4.4 GLP Protocol and Sampling......Page 439
16.4.5 Ensure Correct Sample Labelling......Page 440
16.4.6 Transport to the Laboratory......Page 441
16.4.7 Sample Receipt and Storage......Page 442
16.4.8 Sample Collection Best Practice......Page 443
16.5.1 What the Regulators Want......Page 444
16.5.2 Preparation of Reference Standards and Solutions......Page 445
16.5.3 Sweep Under the Carpet or Own Up to a Mistake......Page 446
16.5.4 What Is the FDA's View of Analyst Mistakes......Page 447
16.6.2 Sample Preparation Current Practices......Page 448
16.6.3 Automate Where Technically Feasible......Page 449
16.7.2 Instruments with No Printer or Data Transfer Capability......Page 450
16.8.1 An Illustrative Analytical Procedure......Page 451
16.8.3 Consider Alternate Analytical Approaches......Page 452
16.9.1 What the Regulators Want......Page 453
16.9.3 Building a Spectral Library......Page 454
16.10 Chromatographic Analysis and CDS Data Interpretation......Page 455
16.10.3 Entering Factors, Weights, and Other Assay Values into the Sequence File......Page 456
16.10.4 An Alternate Approach to Weights and Factors......Page 458
16.10.5 System Evaluation Injections......Page 459
16.10.6 System Suitability Tests – What the Regulators Want......Page 460
16.10.7 Integrating Chromatograms......Page 461
16.10.8 General Principles for Ensuring Good Chromatographic Integration......Page 462
16.10.9 SOP for Integration of Chromatograms......Page 463
16.10.10 Bioanalytical Guidance for Integration of Chromatograms......Page 466
16.10.11 Incomplete (Aborted) Runs......Page 467
16.10.14 Chromatography Falsification Practices 1: Peak Shaving and Enhancing......Page 468
16.10.15 Chromatography Falsification Practices 2: Inhibiting Integration......Page 469
16.11 Calculation of Reportable Results......Page 470
16.11.1 What the Regulators Want......Page 471
16.11.2 General Considerations for Calculations......Page 472
16.11.4 Calculation of Reportable Results and Out of Specification Results......Page 473
References......Page 474
Chapter 17 - Second Person Review......Page 477
17.1.3 EU GMP Annex 11......Page 478
17.1.5 FDA Guidance on Data Integrity and cGMP Compliance......Page 479
17.1.6 WHO Guidance on Good Data and Record Management Practices......Page 481
17.2.1 21 CFR 211......Page 482
17.2.3 FDA Guidance for Industry on Investigating OOS Test Results......Page 483
17.2.6 OOS Regulatory Summary......Page 484
17.3.2 The Scope of the Procedure......Page 485
17.3.3 The Troika of Record Review......Page 486
17.3.6 Training for Second Person Review......Page 487
17.4.2 Improving Manual Analytical Procedures......Page 488
17.4.3 Witness Testing or Second Person Review......Page 489
17.5.1 Loss on Drying Analysis......Page 490
17.5.2 Review of the Second Person Review of the Analytical Records......Page 491
17.6.2 Technical Versus Procedural Controls for Second Person Review......Page 493
17.6.3 The Scope of an Analytical Procedure Involving a Hybrid System......Page 494
17.6.4 Technical Controls to Aid a Second Person Review......Page 495
17.6.6 Recording the Work Performed and the Review......Page 496
17.6.7 Original Record or True Copy......Page 497
17.6.9 Review of Electronic Records, Metadata and Audit Trail......Page 498
17.6.11 Do You Really Want to Work This Way......Page 499
17.7.1 MHRA GXP Data Integrity Guidance and Definitions......Page 500
17.7.3 How Regular Is a Regular Review of Audit Trail Entries......Page 501
17.8.1 LIMS Interfaced with a CDS......Page 504
17.8.2 A Second Person Review Is Process Not System Centric......Page 506
17.9 Recording and Investigating Out of Specification Results......Page 509
17.9.1 Phase 1: Initial OOS Laboratory Investigation......Page 510
17.9.3 Phase 2B Additional Laboratory Testing......Page 512
References......Page 513
18.1.1 WHO Guidance on Good Data and Record Management Practices......Page 515
18.1.3 GLP Regulations: 21 CFR 58......Page 516
18.1.5 21 CFR 11 Requirements......Page 517
18.1.7 FDA Guidance on Data Integrity and cGMP Compliance......Page 518
18.1.9 FDA Guidance for Industry Part 11 – Scope and Application Guidance......Page 519
18.1.11 OECD GLP Regulations......Page 520
18.1.13 Regulatory Requirements Summary......Page 521
18.2.1 JCAMP-DX Data Format for Spectroscopy......Page 522
18.2.3 Progress Towards Universal Data File Formats......Page 523
18.3.1 Backup Is Not Archive (Unless You Are the FDA)......Page 524
18.3.2 Organising Electronic Records to Retain......Page 525
18.3.3 Options for Electronic Archive......Page 526
18.3.4 Can I Read the Records......Page 527
18.3.6 Selection of Off-line Archive Media......Page 528
18.3.9 Assessment of Option Feasibility......Page 529
18.4.1 Definitions......Page 530
18.4.3 Archive Facilities......Page 531
18.4.4 Archiving Electronic Records......Page 532
References......Page 534
19.1.1 EU GMP Chapter 6 Quality Control......Page 536
19.1.3 WHO Guidance on Good Data and Record Management Practices......Page 537
19.1.4 PIC/S PI-041 Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments......Page 538
19.2 KPIs and Metrics for the Laboratory......Page 539
19.2.2 Metrics Must Be Generated Automatically......Page 540
19.2.4 Do Quality Metrics Lead Behaviour......Page 541
19.3.1 Overview: Start Small and Expand......Page 543
19.4.1 Data Integrity Policy and Associated Procedures......Page 544
19.4.2 Assessment of Processes and Systems......Page 545
19.4.3 Executed Remediation Plans......Page 546
19.5.1 Some Preliminary Considerations for Laboratory Data Integrity Metrics......Page 548
19.6 Quality Assurance DI Metrics......Page 549
19.7.1 Management Are Responsible for Data Integrity and the PQS......Page 550
References......Page 551
20.1.1 WHO Guidance on Good Data and Record Management Practices......Page 553
20.1.2 PIC/S PI-041 Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments......Page 554
20.2 Data Integrity Problem or Concern......Page 555
20.3.2 Communicate and Train How to Raise Data Integrity Concerns......Page 556
20.3.6 Confidentiality......Page 557
20.4.2 How to Raise a Concern......Page 558
20.4.4 What the Organisation Must Do......Page 559
References......Page 560
21.1.1 EU GMP Chapter 9 Self-inspections......Page 561
21.1.3 FDA Compliance Program Guide 7346.832 for Pre-approval Inspections......Page 562
21.1.5 MHRA GXP Data Integrity Guidance and Definitions......Page 563
21.1.6 WHO Guidance on Good Data and Record Management Practices......Page 564
21.1.7 PIC/S-PI-041 Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments......Page 565
21.1.8 Regulatory Compliance Summary......Page 566
21.2.2 What Are the Objectives of a Laboratory Data Integrity Audit......Page 567
21.2.4 What Is the Order and Frequency of Audit......Page 568
21.2.6 Data Integrity Audits and Periodic Reviews of Computerised Systems......Page 570
21.2.7 Procedure and Checklist for a Data Integrity Audit......Page 571
21.3.1 Relationship Between the Data Integrity Model and a Data Integrity Audit......Page 572
21.3.2 Overview of the Analytical Process for a Laboratory Data Integrity Audit......Page 573
21.3.4 Auditing Records and Data from Sampling to Report......Page 575
21.3.5 Checking the Configuration Settings of Computerised Systems......Page 577
21.3.7 Photographs to Support Audit Observations and Findings......Page 578
21.4.1 Forensic Data Analysis......Page 579
21.4.2 Recovery of Deleted Files......Page 580
21.5 Triggers for a Data Integrity Investigation......Page 581
References......Page 582
22.1 What the Regulators Require......Page 583
22.1.1 WHO Guidance on Good Data and Record Management Practices......Page 584
22.1.3 FDA Application Integrity Policy......Page 585
22.1.4 PIC/S PI-041 Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments......Page 586
22.1.5 Summary of Data Investigation Regulations and Guidance......Page 587
22.2.2 Sequester a Copy of the System and the Data......Page 589
22.2.5 Time Frame of the Potential Data Integrity Vulnerability......Page 590
22.2.7 Informing Regulatory Authorities......Page 591
22.3.1 Case Study Background......Page 592
22.3.2 Meeting the Intent of the Application Integrity Policy......Page 593
22.3.4 Approaches to the Investigation of Laboratory Data Integrity Issues......Page 595
22.3.6 Investigation of Tests Using Observation......Page 596
22.3.8 Investigation of Analytical Testing by Chromatography......Page 597
22.3.9 Staff Interviews......Page 598
22.3.10 Findings and Their Classification......Page 599
22.3.11 Root Cause of Data Integrity and Poor Data Management Practices......Page 602
22.3.12 Assessment of Material Impact......Page 605
22.3.13 CAPA Plans: Short-term Remediation and Long-term Solutions......Page 606
References......Page 607
23.1.1 WHO Guidance on Good Data and Record Management Practices......Page 609
23.1.2 PIC/S PI-041 Good Practices for Data Management and Integrity in Regulated GMP/GDP Environments......Page 611
23.1.3 Regulatory Guidance Summary......Page 613
23.2 Cetero Research Laboratories Data Falsification Case......Page 614
23.3.1 Current Approaches to Laboratory Audit......Page 615
23.4 Initial Data Integrity Assessment of a Facility......Page 616
23.4.1 Initial Selection of the Contract Laboratory......Page 617
23.4.3 Request for Pre-audit Information......Page 618
23.4.5 Data Governance and Data Integrity in the Context of a PQS......Page 619
23.4.6 Investigate Electronic Record Controls......Page 620
23.4.7 Conclusion of the Audit......Page 621
23.5.1 Main Data Integrity Contractual Responsibilities......Page 622
23.6 On-going Monitoring of Work and Audits......Page 623
23.6.2 Monitoring the Results......Page 624
23.6.4 On-site Audits......Page 625
References......Page 626
24.1.1 EU GMP Chapter 9 Self-inspections......Page 627
24.2 Audit Aide Memoire for the Foundation Layer: Data Governance......Page 628
24.2.1 Management Leadership for Data Integrity......Page 629
24.2.3 Data Integrity Training......Page 630
24.2.6 Establishment and Maintenance of an Open Culture......Page 632
24.4 Audit Aide Memoire for Level 2: Analytical Procedure Validation Life Cycle......Page 633
24.4.1 Procedure Design (Method Development)......Page 636
24.5 Level 3: Study and Batch Analysis Data Integrity Aide Memoire......Page 638
24.5.1 Routine Analysis Data Integrity Aide Memoire......Page 639
24.6 Quality Assurance Oversight Aide Memoire......Page 641
24.6.2 Data Integrity Audits......Page 644
References......Page 646
Subject Index......Page 648