Quality control training manual : comprehensive training guide for API, finished pharmaceutical and biotechnologies laboratories

430 Pages·2011·2.68 MB·English

by  Syed Imtiaz Haider

Quality Control
Training Manual
Comprehensive Training Guide for API,
Finished Pharmaceutical
and Biotechnologies Laboratories
Quality Control
Training Manual
Comprehensive Training Guide for API,
Finished Pharmaceutical
and Biotechnologies Laboratories
Syed Imtiaz Haider • Erfan Syed Asif
CRC Press
Taylor & Francis Group
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Boca Raton, FL 33487-2742
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To Mr. Saleem Riaz, the ex-Director of Quality Assurance,
Abbott Laboratories, Pakistan, for his commitment to establish
quality as an attitude in the pharmaceutical industry
Syed Imtiaz Haider
Erfan Syed Asif
Contents
Preface...............................................................................................................xvii
Acknowledgements ............................................................................................xix
Authors ...............................................................................................................xxi
About the Book ................................................................................................xxiii
Disclaimer .......................................................................................................xxvii
QCT-01 Analytical Methods, Techniques and Quality Measures
for General Pharmaceutical Products ...........................................1
QCT-01.1 Analytical Method Validation and Requirements ........................3
Test Methods and Standards .........................................................3
Test Method Validation .................................................................3
Test Method Transfer ....................................................................4
Change Control .............................................................................4
Quality Standards Manual ............................................................5
Laboratory Procedures..................................................................5
Training .........................................................................................6
Testing ...........................................................................................7
Raw Data .......................................................................................7
Cleaning Validation ......................................................................8
Raw Material.................................................................................8
QCT-01.2 Laboratory Equipment ..................................................................9
Calibration and Maintenance ........................................................9
Documentation ............................................................................10
Cleaning ......................................................................................11
Qualifi cation of the Equipment ...................................................11

Columns’ Records .......................................................................12
Columns’ Evaluation ...................................................................13
Change Control ...........................................................................13
QCT-01.3 Reference Standards and Reagents .............................................15
USP and Other Pharmacopoeial Standards ................................15
Reagents, Standardized Volumetric Solution and Buffers ..........16
Procedure for Internal Working Standards
(Secondary Reference Standards) Preparation ...........................16
Stock Solutions, Working and Test Solution ...............................18
vii
viii Contents
Expiration and Retest Dates for Standards and Reagents ...........18
Storage ........................................................................................18
Labelling .....................................................................................19
QCT-01.4 Sample Management ...................................................................21
Raw Materials, Finished Products, In-Process,
Validation, Swab, Water, Air, Complaint....................................21
QCT-01.5 Stability Analytical Methods and Requirements ........................25
Written Procedures .....................................................................25
On Site Starts ..............................................................................26
Time and Frequencies .................................................................26
Statistical Considerations ............................................................27
Evaluation of Stability ................................................................27
Specifi cations and Methods ........................................................28
Stability Methods ........................................................................30
Stability Methods Validation Program .......................................30
Technology Transfer ...................................................................30
Change Control ...........................................................................31
Raw Data .....................................................................................31
Training Effectiveness ................................................................31
Analyst-Specifi c Training ...........................................................32
Training Documentation .............................................................32
Stability Chambers .....................................................................33
Outside Laboratories ...................................................................33
QCT-01.6 Microbiological Methods and Analysis ......................................35
Microbiological Methods and Testing ........................................35
Microbiological Testing for Non-Sterile Products ......................35
Growth Promotion Testing ..........................................................36
Media Preparation and Sterilization ...........................................36
Outside Vendor–Supplied Media ................................................37
Aseptic Technique Training ........................................................37
Gowning ......................................................................................38
Sterility Testing ...........................................................................38
Automated Identifi cation Systems ..............................................39
Sterility Testing Facilities ...........................................................39
Environmental Monitoring during Sterility Testing ...................40
Water Monitoring Data ...............................................................40
Compressed Air for Sterile Area ................................................41
Nitrogen Testing for Sterile Area ................................................41
Oxygen Testing for Sterile Area .................................................41
Contents ix
Preservative Effectiveness Testing ..............................................42
Bacterial Endotoxin Testing for Sterile Products .......................42
QCT-01.7 Analytical Failure Investigations ................................................43
Laboratory Investigations ...........................................................43
OOS Investigations .....................................................................44
Training on OOS Procedure .......................................................47
Training Documentation .............................................................47
QCT-01.8 Calibration Program ...................................................................49
QC Instruments Calibration ........................................................49
Calibration Procedure .................................................................50
Calibration Frequency .................................................................51
Documentation ............................................................................52
QCT-01.9 Laboratory Facility .....................................................................53
General Requirements ................................................................53
Area for Handling Test and Reference Substances .....................54
Areas for Routine Samples after Complete Testing ....................54
Reference Samples after Expiry .................................................55
Archive Room .............................................................................55
Storage of Bacterial Strains ........................................................56
Cleaning, Disinfecting and Washing Glass Apparatus ...............56
Utilities ........................................................................................57
Safety Shower .............................................................................57
QCT-01.10 Products Annual Reviews ...........................................................59
Annual Reviews ..........................................................................59
Written Procedures .....................................................................59
Management Review ...................................................................60

Data Reliability ...........................................................................61
Use of Ongoing Statistics ............................................................61
Follow-up ....................................................................................61
QCT-01.11 Third-Party Testing .....................................................................63
General ........................................................................................64
QCT-01.12 Good Documentation Practices ..................................................65
Documentation ............................................................................65
Procedure ....................................................................................65
x Contents
QCT-01.13 Change Control ...........................................................................67
Unplanned Changes ....................................................................68
Planned Changes .........................................................................68
Routine Changes (Documentation) .............................................68
QCT-02 Analytical Methods, Techniques and Quality Measures
for Biological Products ...............................................................71
QCT-02.1 Immunoblotting ..........................................................................73
Immunoblotting Analytical Technique .......................................73
Procedure ....................................................................................74
Enhanced Chemiluminescence ...................................................76
QCT-02.2 Gel Permeation Chromatography ...............................................79
Basic Philosophy .........................................................................79
Mechanism of Gel Permeation Chromatography .......................81
Advantages of GPC .....................................................................81
Disadvantages .............................................................................82
QCT-02.3 Electrophoresis ............................................................................85
Gel Electrophoresis .....................................................................85
DNA Electrophoresis ..................................................................86
One-Dimensional (1D) Electrophoresis ......................................87
Two-Dimensional (2D) Electrophoresis ......................................88
Capillary Electrophoresis ...........................................................88
Capillary Zone Electrophoresis ..................................................90
Capillary Gel Electrophoresis .....................................................90
Capillary Isoelectric Focusing ....................................................90
QCT-02.4 Ion-Exchange Chromatography ..................................................93

Effect of Charge on the Protein Molecule ..................................94
Protein Separation by IEC ..........................................................95
Anion-Exchange Chromatography .............................................96
Cation-Exchange Chromatography .............................................96
QCT-03 Laboratory Training Manual ......................................................99
QCT-03.1 Laboratory Safety and Good Laboratory Practice ....................101
Procedure ...................................................................................101
Good Laboratory Practices .......................................................104
Contents xi
QCT-03.2 Training of Sampling Procedure...............................................107
Procedure ..................................................................................107
QCT-03.3.1 Training of Conventional Procedures ........................................113
Procedure ...................................................................................113
QCT-03.3.2 Training of Basic Analytical Techniques ..................................115
Weighing ....................................................................................115
Volumetric Techniques ..............................................................116
Defi nitions ..................................................................................116
Use of Burette ............................................................................116
Temperature Measurement and Control ....................................117
Heating .......................................................................................117
Cooling .......................................................................................117
Mechanical Methods of Separation ...........................................117
Limit Tests .................................................................................118
Determination of Weight per Millilitre Density/Solids .............119
Physical Observations ...............................................................120
QCT-03.3.3 Training of Chromatographic Techniques ................................121
Testing to Specifi cation/Practical Work ...................................121
Chromatographic Techniques ...................................................121
HPLC Pumping System ............................................................122
Injectors ....................................................................................123
Columns ....................................................................................123
Detectors ...................................................................................124
Solvents and Reagents ...............................................................125
Data Handling and Interpretation .............................................125
Gas Chromatography ................................................................126
Sample Injection .......................................................................126
Types of Columns .....................................................................126
Injectors ....................................................................................127
Detectors ...................................................................................127
Procedure ..................................................................................127
QCT-03.3.4 Spectroscopic Techniques ..........................................................131
UV Absorption and Colorimetry ...............................................131
Infrared Spectrophotometry .....................................................132
Atomic Absorption Spectrometry .............................................132
Instrumentation .........................................................................133
Sample Preparation and Vaporization ......................................134
xii Contents
Interferences and Quantitative Measurements..........................134
Trainee Assessment ..................................................................135
Flame Emission Spectrometry ..................................................135
Sample Preparation and Vaporization ......................................136
Interference and Quantitative Measurements ...........................136
Trainee Assessment ..................................................................137
QCT-03.3.5 Electrochemical Techniques .....................................................139
pH Measurement and Ion-Selective Electrodes ........................139
Potentiometer Titrations, if Available .......................................140
Biamperometric Titrations ........................................................140
Karl Fischer Titrations ..............................................................140
Automatic Titrations ..................................................................141
QCT-03.3.6 Dissolution Test ..........................................................................143
QCT-03.3.7 Miscellaneous Techniques ........................................................145
Polarimetry ...............................................................................145
Particle Size Analysis ...............................................................146
Suppository Penetration Tester .................................................146
Viscometry .................................................................................147
Other Analytical Techniques .....................................................147
QCT-04 Assessment of Training .............................................................149
QCT-04.1 Assessment Procedure for Chemical Testing ...........................151
Procedure ..................................................................................151
Use of Balance and Volumetric Techniques .............................151
Titration with 1.0 M Hydrochloric Acid ...................................151
Quantitative Transfer of Sodium Hydroxide .............................152

Temperature Measurement and Control ...................................152
Solvent Extraction Exercise ......................................................153
Exercise for Limit Tests ............................................................153
Determination of Weight per mL and Density of Solid ............155
Physical Observation .................................................................155
Testing to Specifi cation/Practical Work ...................................155
Chromatographic Techniques ...................................................155
Assessment Procedures for GC and HPLC ..............................156
Test Procedure...........................................................................157
Criteria for Assessment .............................................................159