Handbook of analytical validation

ANALYTICAL VALIDATION......Page 3
Contents......Page 6
Preface......Page 14
1.2 Drug Development Process......Page 16
1.3 FDA Hierarchy and Organization......Page 18
1.4 International Conference on Harmonization......Page 19
1.4.1 Structure of the Ich......Page 20
1.4.1.6 Pharmaceutical research and manufacturers of America phrmA......Page 21
1.4.3.1 step 1......Page 22
1.4.3.5 step 5......Page 23
1.5 AMV Guidance......Page 24
1.5.6.1 Selection and shipment of samples......Page 28
1.5.6.2 Responsibilities......Page 29
1.6 Validation Process......Page 30
1.7 Training......Page 33
References......Page 35
2.2 Components of Data Quality......Page 38
2.3.1 Design Qualification......Page 39
2.3.2 Installation Qualification IQ......Page 40
2.3.3 Operational Qualification OQ......Page 41
2.3.3.1 Hplc pump Flow rate Accuracy......Page 42
2.3.3.3 Injector Accuracy......Page 43
2.3.3.4 column oven and Auto sampler temperature......Page 44
2.3.3.5 uv detector Wavelength Accuracy and linearity......Page 45
2.3.5 Preventative Maintenance and Repairs......Page 47
2.6 AIQ Documentation......Page 49
2.7 Instrument Categories......Page 50
References......Page 51
3.2 HPLC Method Development Approaches......Page 52
3.3 Method Goals......Page 53
3.4 Hplc metHod development InstrumentAtIon......Page 54
3.4.1 HPLC Systems for Column and Method Scouting......Page 59
3.4.2 Automated HPLC Method Development Systems......Page 62
3.4.3 UHPLC in Method Development Systems......Page 64
3.4.4 Solvent Management......Page 65
3.4.6 Detection......Page 66
3.4.7 Column Module......Page 70
3.4.8 Columns for Method Development......Page 71
3.4.9 Mobile Phase Considerations......Page 72
3.5 Method Optimization......Page 73
Preferences......Page 74
4.2 Method Validation Guidelines......Page 76
4.3 Terms and Definitions......Page 77
4.3.1 Accuracy......Page 78
4.3.2.2 Intermediate Precision......Page 80
4.3.2.3 Reproducibility......Page 81
4.3.2.4 Ruggedness......Page 82
4.3.3 Specificity......Page 83
4.3.4 Detection Limit......Page 85
4.3.5 Quantitation Limit......Page 86
example minimum recommended ranges......Page 88
4.3.7 Robustness......Page 89
4.5 Documentation......Page 90
References......Page 93
5.2 Robustness Studies for Method Validation......Page 96
5.3.1 Screening Designs......Page 98
5.3.1.2 Fractional Factorial deigns......Page 99
5.3.2 Determining the Factors Measuring the Results......Page 101
5.4 Analyzing the Results......Page 104
5.5 Documentation and Reporting......Page 105
5.6 System Suitability Tests......Page 106
5.7 System Suitability Standards......Page 107
5.8 System Suitability Protocol......Page 108
5.9 Method Adjustments to Meet System Suitability Requirements......Page 109
5.10 Conclusion......Page 113
References......Page 114
6.2 Guidance for Setting Specifications......Page 116
6.3.1 Limited Data Available at Filing......Page 117
6.3.6 Pharmacopeial  Tests......Page 118
6.5.3 Polymorphic Forms......Page 119
6.5.7 Inorganic Impurities......Page 120
6.6.3 Hardness/Friability......Page 121
6.8 Specific Tests/Criteria: Parenteral Drug Products......Page 122
6.10 OOS Background......Page 123
6.12 Identifying and Assessing OOS Test Results......Page 126
6.13.2 Laboratory Phase of an Investigation......Page 128
6.13.2.1 Assignable cause......Page 129
6.13.4 Resampling......Page 130
6.14 Concluding the OOS Investigation......Page 131
References......Page 132
8.2 Terms, Definitions, and Responsibilities......Page 180
8.3 Analytical Method Transfer Options......Page 181
8.3.4 Transfer Waiver......Page 182
8.4.3 Descripton and Rationale of Test Requirements......Page 183
8.6 Potential AMP Pitfalls......Page 184
8.6.1 Instrument Considerations......Page 186
8.7 Conclusion......Page 187
References......Page 188
9.2 Changes to and Approved Method......Page 190
9.3 What Constitutes a Change to a Method?......Page 191
9.4.1 Verification......Page 192
9.4.1.3 verification documentation......Page 193
9.4.1.4 verification process examples......Page 194
9.5 Implement and Existing Standard Method with Adjustments......Page 195
9.6 Implement an Existing Standard Method with Changes......Page 196
References......Page 197
Glossary of Terms Related to Chromatographic Method Validation......Page 198
Appendix: Example Method Validation Protocol......Page 206
A.4.1 Analysis......Page 207
A.4.6 Precision Repeatability and Intermediate......Page 208
A.5.1 System Suitability......Page 209
A.5.8 Degradant LOQ......Page 210
A.8 Data Recording......Page 211
A.12 Appendices......Page 212
Index......Page 214