Good Manufacturing Practices for Pharmaceuticals: A Plan for Total Quality Control from Manufacturer to Consumer: Fifth Edition,

735 Pages·2000·8.857 MB·English

by  Joseph, D. Nally

Good Manufacturing Practices
for Pharmaceutical
A Plan far Total Quality Control
Irani Manufacturer to Consomer
Fifth Edition, Revised and Expended
Sidney H. Wig
Temple University
Philadelphia, Pennsylvania
n
MARCEL
MARCEL DEKKER, INC. NEW YORK • BASEL
DEKKER
Copyright 2001 by Marcel Dekker, Inc. All Rights Reserved.
The preceding edition of this book was published as Good Manufacturing
PracticesforPharmaceuticals:APlanforTotalQualityControl,FourthEdition,
Revised and Expanded, by Sidney H. Willig and James R. Stoker.
ISBN: 0-8247-0425-8
This book is printed on acid-free paper.
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PRINTED IN THE UNITED STATES OF AMERICA
Copyright 2001 by Marcel Dekker, Inc. All Rights Reserved.
DRUGSANDTHEPHARMACEUTICALSCIENCES
ExecutiveEditor
James Swarbrick
PharmaceuTech,Inc.
Pinehurst,NorthCarolina
AdvisoryBoard
LarryL.Augsburger DavidE.Nichols
UniversityofMaryland PurdueUniversity
Baltimore,Maryland WestLafayette,Indiana
DouweD.Breimer StephenG.Schulman
GorlaeusLaboratories UniversityofFlorida
Leiden,TheNetherlands Gainesville,Florida
TrevorM.Jones JeromeP.Skelly
TheAssociationofthe Alexandria,Virginia
BritishPharmaceuticalIndustry
London,UnitedKingdom
HansE.Junginger FelixTheeuwes
Leiden/AmsterdamCenter AlzaCorporation
forDrugResearch PaloAlto,California
Leiden,TheNetherlands
VincentH.L.Lee GeoffreyT.Tucker
UniversityofSouthernCalifornia UniversityofSheffield
LosAngeles,California RoyalHallamshireHospital
Sheffield,UnitedKingdom
PeterG.Welling
InstitutdeRechercheJouveinal
Fresnes,France
Copyright 2001 by Marcel Dekker, Inc. All Rights Reserved.
DRUGSANDTHEPHARMACEUTICALSCIENCES
ASeriesofTextbooksandMonographs
1. Pharmacokinetics,MiloGibaldiandDonaldPerrier
2. Good Manufacturing Practices for Pharmaceuticals: A Plan for Total
Quality Control, Sidney H. Willig, Murray M. Tuckerman, and William
S.HitchingsIV
3. Microencapsulation,editedbyJ.R.Nixon
4. Drug Metabolism: Chemical and Biochemical Aspects, Bernard Testa
andPeterJenner
5. NewDrugs:DiscoveryandDevelopment,editedbyAlanA.Rubin
6. Sustained and Controlled Release Drug Delivery Systems, edited by
JosephR.Robinson
7. Modern Pharmaceutics, edited by Gilbert S. Banker and Christopher
T.Rhodes
8. Prescription Drugs in Short Supply: Case Histories, Michael A.
Schwartz
9. Activated Charcoal: Antidotal and Other Medical Uses, David O.
Cooney
10. Concepts in Drug Metabolism (in two parts), edited by Peter Jenner
andBernardTesta
11. Pharmaceutical Analysis: Modern Methods (in two parts), edited by
JamesW.Munson
12. TechniquesofSolubilizationofDrugs,editedbySamuelH.Yalkowsky
13. OrphanDrugs,editedbyFredE.Karch
14. Novel Drug Delivery Systems: Fundamentals, Developmental Con-
cepts,BiomedicalAssessments,YieW.Chien
15. Pharmacokinetics: Second Edition, Revised and Expanded, Milo
GibaldiandDonaldPerrier
16. Good Manufacturing Practices for Pharmaceuticals: A Plan for Total
Quality Control, Second Edition, Revised and Expanded, Sidney H.
Willig,MurrayM.Tuckerman,andWilliamS.HitchingsIV
17. FormulationofVeterinaryDosageForms,editedbyJackBlodinger
18. Dermatological Formulations: Percutaneous Absorption, Brian W.
Barry
19. The Clinical Research Process in the Pharmaceutical Industry, edited
byGaryM.Matoren
20. MicroencapsulationandRelatedDrugProcesses,PatrickB.Deasy
21. Drugs and Nutrients: The Interactive Effects, edited by Daphne A.
RoeandT.ColinCampbell
22. BiotechnologyofIndustrialAntibiotics,ErickJ.Vandamme
23. Pharmaceutical Process Validation, edited by Bernard T. Loftus and
RobertA.Nash
Copyright 2001 by Marcel Dekker, Inc. All Rights Reserved.
24. AnticancerandInterferonAgents:SynthesisandProperties,editedby
RaphaelM.OttenbriteandGeorgeB.Butler
25. Pharmaceutical Statistics: Practical and Clinical Applications, Sanford
Bolton
26. Drug Dynamics for Analytical, Clinical, and Biological Chemists,
Benjamin J. Gudzinowicz, Burrows T. Younkin, Jr., and Michael J.
Gudzinowicz
27. ModernAnalysisofAntibiotics,editedbyAdjoranAszalos
28. SolubilityandRelatedProperties,KennethC.James
29. Controlled Drug Delivery: Fundamentals and Applications, Second
Edition, Revised and Expanded, edited by Joseph R. Robinson and
VincentH.Lee
30. New Drug Approval Process: Clinical and Regulatory Management,
editedbyRichardA.Guarino
31. Transdermal Controlled Systemic Medications, edited by Yie W.
Chien
32. Drug Delivery Devices: Fundamentals and Applications, edited by
PraveenTyle
33. Pharmacokinetics: Regulatory · Industrial · Academic Perspectives,
editedbyPeterG.WellingandFrancisL.S.Tse
34. ClinicalDrugTrialsandTribulations,editedbyAllenE.Cato
35. Transdermal Drug Delivery: Developmental Issues and Research Ini-
tiatives,editedbyJonathanHadgraftandRichardH.Guy
36. Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms,
editedbyJamesW.McGinity
37. Pharmaceutical Pelletization Technology, edited by Isaac Ghebre-
Sellassie
38. GoodLaboratoryPracticeRegulations,editedbyAllenF.Hirsch
39. Nasal Systemic Drug Delivery, Yie W. Chien, Kenneth S. E. Su, and
Shyi-FeuChang
40. Modern Pharmaceutics: Second Edition, Revised and Expanded,
editedbyGilbertS.BankerandChristopherT.Rhodes
41. Specialized Drug Delivery Systems: Manufacturing and Production
Technology,editedbyPraveenTyle
42. Topical Drug Delivery Formulations, edited by David W. Osborne and
AntonH.Amann
43. DrugStability:PrinciplesandPractices,JensT.Carstensen
44. Pharmaceutical Statistics: Practical and Clinical Applications, Second
Edition,RevisedandExpanded,SanfordBolton
45. Biodegradable Polymers as Drug Delivery Systems, edited by Mark
ChasinandRobertLanger
46. Preclinical Drug Disposition: A Laboratory Handbook, Francis L. S.
TseandJamesJ.Jaffe
47. HPLC in the Pharmaceutical Industry, edited by Godwin W.Fong and
StanleyK.Lam
48. PharmaceuticalBioequivalence,editedbyPeterG.Welling,FrancisL.
S.Tse,andShrikantV.Dinghe
49. PharmaceuticalDissolutionTesting,UmeshV.Banakar
50. Novel Drug Delivery Systems: Second Edition, Revised and
Expanded,YieW.Chien
51. Managing the Clinical Drug Development Process, David M. Coc-
chettoandRonaldV.Nardi
52. Good Manufacturing Practices for Pharmaceuticals: A Plan for Total
Quality Control, Third Edition, edited by Sidney H. Willig and James
R.Stoker
53. Prodrugs: Topical and Ocular Drug Delivery, edited by Kenneth B.
Sloan
54. Pharmaceutical Inhalation Aerosol Technology, edited by Anthony J.
Hickey
55. Radiopharmaceuticals: Chemistry and Pharmacology, edited by
AdrianD.Nunn
56. NewDrugApprovalProcess:SecondEdition,RevisedandExpanded,
editedbyRichardA.Guarino
57. Pharmaceutical Process Validation: Second Edition, Revised and Ex-
panded,editedbyIraR.BerryandRobertA.Nash
58. OphthalmicDrugDeliverySystems,editedbyAshimK.Mitra
59. Pharmaceutical Skin Penetration Enhancement, edited by Kenneth A.
WaltersandJonathanHadgraft
60. ColonicDrugAbsorptionandMetabolism,editedbyPeterR.Bieck
61. Pharmaceutical Particulate Carriers: Therapeutic Applications, edited
byAlainRolland
62. Drug Permeation Enhancement: Theory and Applications, edited by
DeanS.Hsieh
63. GlycopeptideAntibiotics,editedbyRamakrishnanNagarajan
64. Achieving Sterility in Medical and Pharmaceutical Products, Nigel A.
Halls
65. MultiparticulateOralDrugDelivery,editedbyIsaacGhebre-Sellassie
66. ColloidalDrugDeliverySystems,editedbyJörgKreuter
67. Pharmacokinetics: Regulatory · Industrial · Academic Perspectives,
SecondEdition,editedbyPeterG.WellingandFrancisL.S.Tse
68. Drug Stability: Principles and Practices, Second Edition, Revised and
Expanded,JensT.Carstensen
69. Good Laboratory Practice Regulations: Second Edition, Revised and
Expanded,editedbySandyWeinberg
70. Physical Characterization of Pharmaceutical Solids, edited by Harry
G.Brittain
71. Pharmaceutical Powder Compaction Technology, edited by Göran Al-
derbornandChristerNyström
72. Modern Pharmaceutics: Third Edition, Revised and Expanded, edited
byGilbertS.BankerandChristopherT.Rhodes
73. Microencapsulation: Methods and Industrial Applications, edited by
SimonBenita
74. OralMucosalDrugDelivery,editedbyMichaelJ.Rathbone
75. Clinical Research in Pharmaceutical Development, edited by Barry
BleidtandMichaelMontagne
76. The Drug Development Process: Increasing Efficiency and Cost Ef-
fectiveness, edited by Peter G. Welling, Louis Lasagna, and Umesh
V.Banakar
77. Microparticulate Systems for the Delivery of Proteins and Vaccines,
editedbySmadarCohenandHowardBernstein
78. Good Manufacturing Practices for Pharmaceuticals: A Plan for Total
Quality Control, Fourth Edition, Revised and Expanded, Sidney H.
WilligandJamesR.Stoker
79. Aqueous Polymeric Coatings for Pharmaceutical Dosage Forms:
Second Edition, Revised and Expanded, edited by James W.
McGinity
80. Pharmaceutical Statistics: Practical and Clinical Applications, Third
Edition,SanfordBolton
81. Handbook of Pharmaceutical Granulation Technology, edited by Dilip
M.Parikh
82. Biotechnology of Antibiotics: Second Edition, Revised and Expanded,
editedbyWilliamR.Strohl
83. MechanismsofTransdermalDrugDelivery,editedbyRussellO.Potts
andRichardH.Guy
84. Pharmaceutical Enzymes, edited by Albert Lauwers and Simon
Scharpé
85. Development of Biopharmaceutical Parenteral Dosage Forms, edited
byJohnA.Bontempo
86. PharmaceuticalProjectManagement,editedbyTonyKennedy
87. Drug Products for Clinical Trials: An International Guide to Formula-
tion· Production · Quality Control, edited by Donald C. Monkhouse
andChristopherT.Rhodes
88. Development and Formulation of Veterinary Dosage Forms: Second
Edition, Revised and Expanded, edited by Gregory E. Hardee and J.
DesmondBaggot
89. Receptor-BasedDrugDesign,editedbyPaulLeff
90. Automation and Validation of Information in Pharmaceutical Pro-
cessing,editedbyJosephF.deSpautz
91. Dermal Absorption and Toxicity Assessment, edited by Michael S.
RobertsandKennethA.Walters
92. Pharmaceutical Experimental Design, Gareth A. Lewis, Didier
Mathieu,andRogerPhan-Tan-Luu
93. Preparing for FDA Pre-Approval Inspections, edited by Martin D.
HynesIII
94. Pharmaceutical Excipients: Characterization by IR, Raman, and NMR
Spectroscopy,DavidE.BugayandW.PaulFindlay
95. PolymorphisminPharmaceuticalSolids,editedbyHarryG.Brittain
96. Freeze-Drying/Lyophilization of Pharmaceutical and Biological Prod-
ucts,editedbyLouisReyandJoanC.May
97. Percutaneous Absorption: Drugs–Cosmetics–Mechanisms–Metho-
dology, Third Edition, Revised and Expanded, edited by Robert L.
BronaughandHowardI.Maibach
98. Bioadhesive Drug Delivery Systems: Fundamentals, Novel Ap-
proaches, and Development, edited by Edith Mathiowitz, Donald E.
ChickeringIII,andClaus-MichaelLehr
99. ProteinFormulationandDelivery,editedbyEugeneJ.McNally
100. New Drug Approval Process: Third Edition, The Global Challenge,
editedbyRichardA.Guarino
101. PeptideandProteinDrugAnalysis,editedbyRonaldE.Reid
102. TransportProcessesinPharmaceuticalSystems,editedbyGordonL.
Amidon,PingI.Lee,andElizabethM.Topp
103. Excipient Toxicity and Safety, edited by Myra L. Weiner and Lois A.
Kotkoskie
104. The Clinical Audit in Pharmaceutical Development, edited by Michael
R.Hamrell
105. Pharmaceutical Emulsions and Suspensions, edited by Francoise
NielloudandGilberteMarti-Mestres
106. Oral Drug Absorption: Prediction and Assessment, edited by Jennifer
B.DressmanandHansLennernäs
107. Drug Stability: Principles and Practices, Third Edition, Revised and
Expanded,editedbyJensT.CarstensenandC.T.Rhodes
108. Containment in the Pharmaceutical Industry, edited by James P.
Wood
109. Good Manufacturing Practices for Pharmaceuticals: A Plan for Total
QualityControlfromManufacturertoConsumer,FifthEdition,Revised
andExpanded,SidneyH.Willig
110. AdvancedPharmaceuticalSolids,JensT.Carstensen
111. Endotoxins: Pyrogens, LAL Testing, and Depyrogenation, Second
Edition,RevisedandExpanded,KevinL.Williams
112. Pharmaceutical Process Engineering, Anthony J. Hickey and David
Ganderton
113. Pharmacogenomics, edited by Werner Kalow, Urs A. Meyer, and Ra-
chelF.Tyndale
114. Handbook of Drug Screening, edited by Ramakrishna Seethala and
PrabhavathiB.Fernandes
115. DrugTargetingTechnology:Physical•Chemical•BiologicalMethods,
editedbyHansSchreier
116. Drug–DrugInteractions,editedbyA.DavidRodrigues
117. Handbook of Pharmaceutical Analysis, edited by Lena Ohannesian
andAnthonyJ.Streeter
118. PharmaceuticalProcessScale-Up,editedbyMichaelLevin
119. Dermatological and Transdermal Formulations, edited by Kenneth A.
Walters
120. Clinical Drug Trials and Tribulations: Second Edition, Revised and
Expanded,editedbyAllenCato,LyndaSutton,andAllenCatoIII
121. Modern Pharmaceutics: Fourth Edition, Revised and Expanded, edi-
tedbyGilbertS.BankerandChristopherT.Rhodes
122. SurfactantsandPolymersinDrugDelivery,MartinMalmsten
123. Transdermal Drug Delivery: Second Edition, Revised and Expanded,
editedbyRichardH.GuyandJonathanHadgraft
124. Good Laboratory Practice Regulations: Second Edition, Revised and
Expanded,editedbySandyWeinberg
125. Parenteral Quality Control: Sterility, Pyrogen, Particulate, and Pack-
age Integrity Testing: Third Edition, Revised and Expanded, Michael
J.Akers,DanielS.Larrimore,andDanaMortonGuazzo
126. Modified-Release Drug Delivery Technology, edited by Michael J.
Rathbone,JonathanHadgraft,andMichaelS.Roberts
127. Simulation for Designing Clinical Trials: A Pharmacokinetic-Pharma-
codynamic Modeling Perspective, edited by Hui C. Kimko and Ste-
phenB.Duffull
128. Affinity Capillary Electrophoresis in Pharmaceutics and Biopharma-
ceutics, edited by Reinhard H. H. Neubert and Hans-Hermann Rüt-
tinger
129. Pharmaceutical Process Validation: An International Third Edition,
Revised and Expanded, edited by Robert A. Nash and Alfred H.
Wachter
130. Ophthalmic Drug Delivery Systems: Second Edition, Revised and
Expanded,editedbyAshimK.Mitra
131. Pharmaceutical Gene Delivery Systems, edited by Alain Rolland and
SeanM.Sullivan
ADDITIONALVOLUMESINPREPARATION
BiomarkersinClinicalDrugDevelopment,editedbyJohnBloom
Pharmaceutical Inhalation Aerosol Technology: Second Edition, Re-
visedandExpanded,editedbyAnthonyJ.Hickey
PharmaceuticalExtrusionTechnology,editedbyIsaacGhebre-Sellas-
sieandCharlesMartin
PharmaceuticalCompliance,editedbyCarmenMedina
Preface
Partisanbickeringin theCongressoftheUnitedStates,with addedhostilitybe-
tweenthePresidentandthelegislature,hasoccasionedmuchnewsmediaatten-
tion in 1999. So, in the United States, as in Europe and Japan, there continues
growingpoliticalappealinpressingdrugmanufacturersforpriceconcessionsin
responsetotheproblemoffundingnationalhealthcaresystems.Thishasadded
to consideration of the economy of drugs, biologicals, vaccines, and medical
devices; a lesser tolerance for growth in research costs; and a greater demand
forreductioninmanufacturingoutlay.MuchhealthyinnovationinCurrentGood
ManufacturingPractices(CGMPs) will occur,but atsome risk.Mediacriticism
of promotional expenses can be anticipated.
Becausethiseditioncontinuesinsightsrequisitetothemultinationalactivi-
ties of most manufacturers today, we take note of scientific and legal factors to
agreaterextentthanbefore.Thetextcontainsguidelinesthataddressthesefactors
andquestionsthatthereaderwillwanttoanalyzeindetailand update.Weurge
our readers to be alert to millennial revisions, additions, and deletions to pub-
lished standards on which they presently rely. For example, in USP24-NF19,
there have been more than 3900 revisions.
Theaudienceforthisbookisbroaderthanjustthoseinvolvedinthemanu-
factureofpharmaceuticals.Thisisaninvaluableresourceforprivateandindepen-
dentinspectionpersonnel,localandstateinspectionagencies,andqualityassur-
ance organizations contracted by distributors, and reflects the growing role of