Pharmaceutical Dosage Forms: Tablets, Second Edition, --Volume 3

Pharmaceutical Dosage Forms......Page 2
PREFACE......Page 4
CONTENTS......Page 7
CONTRIBUTORS......Page 9
CONTENTS OF PHARMACEUTICAL DOSAGE FORMS: PARENTERAL MEDICATIONS, SECOND EDITION, REVISED AND EXPANDE.........Page 11
CONTENTS OF PHARMACEUTICAL DOSAGE FORMS: TABLETS, SECOND EDITION, REVISED AND EXPANDED, VOLUMES 1–3......Page 13
CONTENTS OF PHARMACEUTICAL DOSAGE FORMS: DISPERSE SYSTEMS, VOLUMES 1 AND 2......Page 15
II. Quality Assurance System.......Page 17
B. Chemical and Microbiological Attributes......Page 18
1. Antibiotics......Page 23
2. Actives Other Than Antibiotics.......Page 25
A. Glass Containers......Page 28
B. Polymeric Containers......Page 30
C. Elastomeric Closures......Page 33
B. Drinking Water......Page 36
C. Purified Water......Page 37
VI. Manufacturing Control.......Page 39
B. Facilities......Page 40
C. Equipment......Page 44
D. Compounding......Page 49
VII. Filling and Sealing Control.......Page 52
A. Control Charts......Page 54
B. Particulate Matter......Page 56
C. Filtration......Page 57
D. Integrity of Seal......Page 59
A. Compendial Requirements......Page 60
B. Quality Assurance During Packaging Operation......Page 61
A. Sampling Procedure......Page 62
1. Single-Sampling Plan.......Page 63
2. Double-Sampling Plan......Page 65
3. Multiple-Sampling Plans......Page 66
B. Specification......Page 70
1. Weight Variation or Content Uniformity......Page 74
2. Particulate Matter In Injections.......Page 75
4. Pyrogen Test......Page 76
5. Sterility Tests......Page 77
C. Reconciliation......Page 78
D. Auditing.......Page 80
Bibliography......Page 81
A. Scientific Purpose.......Page 83
B. Regulatory Purpose......Page 84
II. Record Content......Page 85
C. What?......Page 86
E. How?......Page 87
A. Records Subject to Inspection.......Page 88
2. Record Retention......Page 89
3. Retrieval Requirements......Page 90
2. Batch Production Records......Page 91
B. Control Records......Page 92
2. Reference Standards......Page 93
C. Validation Records......Page 94
1. Protocol......Page 95
3. Qualification......Page 96
4. Computer Validation.......Page 99
6. Supplier Validation......Page 102
7. Analytical Validation......Page 103
D. Standard Operating Procedures......Page 104
1. Preparation......Page 105
3. Procedure Distribution......Page 106
1. Receiving......Page 107
3. Testing.......Page 108
5. Vendor Approval......Page 109
1. Material and Equipment Verification......Page 110
3. Sterilization.......Page 111
4. Leak Testing......Page 112
G. Environmental Monitoring......Page 113
H. Finishing Operations......Page 115
1. Material Examination and Usage......Page 116
2. Packaging Operations.......Page 117
3. Record Review......Page 119
2. Equipment Cleaning and Maintenance Records......Page 120
4. Reprocessing Records.......Page 121
6. Returned Goods Documentation......Page 122
3. Health Records......Page 123
1. Investigation of Deviations......Page 124
3. Trend Analysis.......Page 125
5. NDA Annual Reports......Page 126
6. Internal Audits......Page 129
8. Advertising/Promotion......Page 130
2. Complaints and Adverse Reactions......Page 131
References......Page 132
I. Introduction.......Page 133
II. Sources of Particulate Matter......Page 134
B. Container......Page 135
C. Closure......Page 137
E. Administration System.......Page 138
III. Biological (Clinical) Significance......Page 139
IV Regulations and Standards......Page 148
V. Methods of Detection, Counting, and Sizing Particles......Page 155
1. Principle......Page 158
3. Description of the Microscope......Page 159
5. Method of Counting Particles......Page 164
7. Advantages and Disadvantages of Microscopic Approaches......Page 166
B. Automated Methods of Monitoring and Sizing.......Page 167
2. Calibration of Electronic Instruments......Page 168
3. Particulate Matter Monitoring by Electrolyte Displacement......Page 170
4. Particulate Matter Monitoring by Light Blockage......Page 172
6. General Advantages and Disadvantages of Instrumental Methods.......Page 175
A. Facilities and Clean-Room Equipment......Page 177
C. Validation of Filtration......Page 178
D. Validation of the Sampling Procedure......Page 179
A. Mounting Media.......Page 180
D. Scanning Electron Microscopy/Energy Dispersive X-Ray Analysis......Page 183
F. Measurement of Refractive Index......Page 185
A. Polarizing Microscopy......Page 186
B. SEM/EDXRA......Page 189
C. Micro X-Ray Powder Diffraction......Page 203
D. Other Microanalytical Methods......Page 204
X. Elimination.......Page 206
XI. Visible Inspection......Page 210
XII. Manual Particulate Inspection......Page 211
B. Manual Inspector Training Programs......Page 214
C. Measurement of Particle Inspection Security......Page 215
E. Definition of Inspection Security for Visible Particles......Page 218
F. Evaluation of Inspectors......Page 224
A. Objective Measures of the Rejection of Visible Particles......Page 225
B. Automatic Transport and Rotation for Manual Inspection......Page 227
C. Fully Automatic Inspection Systems.......Page 232
D. Validation of Alternative Manual, Semi-, and Fully Automatic Inspection Systems......Page 235
E. Inspection Replications for 95% Confidence Limit Validations......Page 236
XIV. Perspectives......Page 239
References......Page 240
A. History......Page 247
B. Definitions......Page 248
E. Calibration......Page 249
F. Qualification.......Page 250
1. Installation Qualification......Page 251
2. Operational Qualification......Page 252
J. Change Control.......Page 253
II. Microbiological Aspects of Sterilization Process Validation......Page 254
A. General Characteristics of Microorganisms that Affect Their Resistance to Sterilization......Page 257
B. The F Concept and Z-Value......Page 261
D. Gas Sterilization......Page 263
E. Radiation Sterilization.......Page 264
III. Steam Sterilization......Page 265
3. Multiple-Pulse Cycles.......Page 266
5. Sterilizer Design......Page 267
C. Validation Outline.......Page 268
D. Steam-in-Place Sterilization......Page 276
2. Condensate Removal......Page 277
IV. Dry-Heat Sterilization and Depyrogenation.......Page 278
B. Dry-Heat Tunnels......Page 279
E. Component Mapping Studies......Page 280
G. Loading Patterns......Page 281
H. Loaded-Chamber Heat-Distribution and Penetration Studies......Page 282
J. Bioburden (or Pyroburden) Determination Studies......Page 283
A. D-Value Determination.......Page 284
C. Loading Patterns......Page 285
2. Gas Concentration and Relative Humidity Distribution......Page 286
G. Pre- and Post-Conditioning......Page 287
A. Stability Studies......Page 288
D. Dose Confirmation......Page 289
A. Validation Program Outline......Page 290
1. Filter/Fluid Compatibility.......Page 291
2. Filter Integrity......Page 292
3. Microbial Challenge Testing......Page 293
5. Bioburden Determination......Page 294
VIII. Aseptic Processing......Page 295
4. Aseptic Filling Operation.......Page 297
1. Sterile Dry Powders......Page 298
IX. Why Validate?......Page 299
X. Conclusion......Page 300
References......Page 301
I. Introduction......Page 304
A. Parenterals in the Food and Drug Act of 1906......Page 305
1. Definitions......Page 306
2. Prohibited Acts and Penalties......Page 307
3. Adulteration Provisions.......Page 310
D. Amendments to the Basic Statute......Page 312
3. Drug Amendments of 1962.......Page 313
4. Orphan Drug Act......Page 315
5. Drug Price Competition and Patent Term Restoration Act of 1984......Page 318
6. Export Drug Act......Page 319
7. Prescription Drug Marketing Act......Page 321
E. Regulations and the Rule-Making Process......Page 323
1. Statutory Authority.......Page 324
2. Promulgation of Regulations......Page 325
4. Guidelines......Page 326
a. Parametric Release—Terminally Heat Sterilized Drug Products......Page 327
b. Fraud, Untrue Statements of Material Facts, Bribery, and Illegal Gratuities.......Page 329
6. Other Acts and/or Executive Orders Affecting Regulations......Page 331
8. Administrative Review......Page 332
1. Investigational New Drugs.......Page 333
2. Treatment Investigational New Drugs......Page 335
3. New Drug Application and Approval......Page 336
4. Post-Approval Obligations......Page 337
5. NDA Supplements......Page 338
a. Abbreviated Applications.......Page 339
b. ANDA Suitability Petitions......Page 340
e. Exclusivity......Page 341
h. Changes to 21 CFR Part 320......Page 342
C. Current Good Manufacturing Practice (CGMP) Regulations......Page 343
1. Provisions of the CGMP Regulations......Page 344
2. Proposed Changes to the CGMP Regulations......Page 347
IV. FDA Enforcement Activities.......Page 351
3. Inspectional......Page 354
3. Inspectional......Page 356
5. Regulatory/Administrative......Page 358
D. Inspections.......Page 359
E. Enforcement Policies and Procedures......Page 360
A. Industry FDA Cooperation......Page 361
B. Freedom of Information......Page 362
1. FDA Recall Guidelines......Page 363
2. Recall of Parenterals......Page 368
A. Impact of Court Review......Page 369
B. Specific Cases Affecting Parenterals......Page 371
References.......Page 374
I. Scope and Objectives......Page 377
B. Internal Audit......Page 378
E. Inspection......Page 379
H. Quality Control (QC)......Page 380
J. Quality Assurance (QA)......Page 381
A. GMPs for Finished Pharmaceuticals (Part 211)......Page 382
C. Good Laboratory Practices (GLPs) Part 58.......Page 385
IV. Role of GMP Audits in QC and QA Programs......Page 386
A. Assuring GMP Compliance......Page 387
B. Detecting Potential Problems......Page 389
D. Increasing Management Awareness......Page 390
V. Elements of a Systematic Audit Program.......Page 392
B. Audit Formats and Approaches......Page 393
1. Checklist Format......Page 394
2. GMP Regulation Format......Page 400
3. Systematic Potential Problem Analysis......Page 402
D. Written SOPs......Page 403
E. Independent Responsibilities......Page 405
F. Planned Periodic Frequency......Page 409
1. Announced Audits......Page 410
1. Defining Auditor Qualifications......Page 411
2. Documenting Auditor Skills......Page 412
3. Selecting Audit Teams......Page 413
4. Maintaining Auditor Awareness Levels......Page 415
1. Preliminary Reports During the Audit.......Page 422
2. Final Reports to Management......Page 424
1. Conclusions and Recommendations......Page 425
1. QA Review......Page 428
2. QC Review......Page 430
3. Production Department Review......Page 432
VI. Conclusion.......Page 434
References......Page 435
I. Introduction......Page 439
II. General Considerations......Page 441
III. Design of Devices......Page 443
A. Function.......Page 444
B. Materials......Page 446
D. Processing and Handling......Page 449
E. Voluntary Standards......Page 455
F. Disposable Versus Multiple Use......Page 457
G. Packaging.......Page 458
A. Plant Environmental Considerations......Page 459
B. Equipment......Page 460
V. Packaging and Labeling......Page 465
VI. Quality Assurance.......Page 466
1. Design......Page 469
2. Manufacture......Page 471
3. Control......Page 472
2. Manufacture......Page 474
1. General Purpose......Page 475
2. Controlled Volume Sets.......Page 477
3. Blood Administration Sets......Page 480
1. Design......Page 482
3. Control......Page 486
1. Design......Page 493
Bibliography......Page 499
I. Control Tests for the Materials Used in Medical Devices......Page 501
A. Formulation Checks and Chemical Assays......Page 502
B. Assurance of Required Physical Properties.......Page 503
2. Routine Toxicity Tests for Batch-to-Batch Release of Devices......Page 504
II. Procedures for Assuring Sterility of Medical Devices......Page 505
1. Environmental Control Over Various Manufacturing Steps.......Page 506
2. Role of Processing Machinery and Fluids on Bioburden......Page 508
3. Control Over Human Contact......Page 509
B. Characterization of Bioburden (Types and Numbers)......Page 510
1. Total Aerobic Microorganisms on Subassemblies and Finished Devices Prior to Sterilization......Page 511
C. Development of Sterilization Cycle.......Page 513
1. Definition of Resistance of Bioburden to a Sterilization Procedure: Derivation of D-Values and Qu.........Page 515
2. Acceptable Estimates of Probabilities of Survivors for Both Parenteral and Nonparenteral Devices......Page 518
3. Radiation Sterilization Cycle Development Using Dosimetric Procedures......Page 519
D. Validation of Effectiveness of Sterilization Procedure (Cycle)......Page 521
1. Validation Approaches for Sterilization Cycle Development......Page 522
2. Generalized Discussion of Sterilization Process Validation per AAMI Guidelines for Industrial Moi.........Page 523
3. Implementation of Sterilization Cycle During Routine Manufacturing Operations......Page 525
3. Resistance of Packaging to Shipping Abuse and Consumer Insults......Page 527
A. Legal Acceptability of the Scientifically Inadequate USP Finished Product Sterility Test......Page 528
B. Use of BI as a Batch Release Mechanism......Page 529
2. Limitations for Inoculated Product BI......Page 530
1. Dosimetric Release of Products Sterilized by Ionizing Radiation......Page 531
2. Process (Dosimetric) Release for Products Sterilized by Steam Under Pressure......Page 533
D. Pyrogen Release Criteria......Page 534
E. Acceptable Levels of Residues from Gaseous EtO Sterilization Procedures......Page 535
G. Adequate Record Keeping for Every Lot of Sterilized Parenteral Devices.......Page 536
References......Page 537
II. History of Drugs and Devices......Page 540
A. Legislative History and Intent.......Page 543
B. Unique Provisions......Page 544
C. Premarket Notification......Page 546
D. Investigational Devices......Page 547
E. Premarket Approval......Page 548
F. Unique Provisions of “Safe Medical Devices Act of 1990”......Page 549
IV. Other Laws.......Page 550
B. Substantive and Interpretive Regulations......Page 552
D. Adulteration......Page 553
E. Misbranding.......Page 554
VI. Agency Procedures......Page 555
B. Communications with Plant Management......Page 556
A. General.......Page 557
D. Detention......Page 558
F. Recall Authority......Page 559
H. Prosecution......Page 560
VIII. Good Manufacturing Practices......Page 561
A. The GMP Regulation......Page 562
Subpart J: Records......Page 563
C. Compliance Program......Page 564
D. Guidelines......Page 565
E. International Activities and Future GMP Applications......Page 566
F. Access to Records Disputes.......Page 567
A. Disposable or Reusable Devices......Page 568
References......Page 569
Bibliography.......Page 570
A......Page 571
B......Page 572
F......Page 573
I......Page 574
M.......Page 575
P......Page 576
Q......Page 578
R......Page 579
S.......Page 581
V......Page 582
W......Page 584