9241546190_index QA GMP Index
Transcript of 9241546190_index QA GMP Index
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Index
Quality assurance of pharmaceuticals, volumes 1 and 2
Notes: (1) Prefixed numbers to page references denote the volume number; forexample, “bioequivalence 1.30, 1.64–65, 2.68” refers to pages 30 and 64–65 in volume1 and page 29 in volume 2. (2) Page numbers in bold type indicate definitions andmain discussions; page numbers in italics refer to tables and other displays.
radioactive and non-radioactiveareas 2.132
to prevent cross-contamination 2.78air-cleanliness levels 2.88–90airborne particulate classification 2.89,
2.90airlocks 2.10, 2.86, 2.100
definition 2.10alkalinity, tests for 1.118allergens 2.103analysts
national laboratories 1.155–156,1.158
training programmes 1.227–235analytical procedures
characteristics 1.120–124, 1.123chemical reference substances 1.125–
131data presentation 1.120infrared spectrophotometry 1.117,
1.125–127, 1.131, 1.136–142residual materials 2.73stability testing 1.54–55training programme 1.227–235types of 1.123, 1.123–124see also basic tests; stability studies;
testsanalytical worksheets 1.166–167,
1.168animals 1.158
care staff 2.105quarters and care 2.31, 2.108
antibiotics 2.60antigens 2.103
accelerated stability studies 1.5–6,1.43–44, 1.48, 1.49–50
test conditions 1.53, 1.53–54see also stability testing
accuracy, analytical procedures1.120–121, 1.123
acidityherbal medicines 1.35tests for 1.118WHO Certification Scheme 1.188,
1.193active ingredient, in herbal medicinal
product 2.128active pharmaceutical ingredients
definition 2.10GMP 2.58–66sterile 2.64
addresses, WHO Certification Scheme1.189, 1.190
administrationlicensing process 1.24–27quality assurance 1.08, 1.109
adverse drug reactions, reports 2.148,2.149
advisory bodies, national drugregulation 1.23
agenciesgovernment drug control
1.109–110quality enforcement 1.108–109
air handling systemsfor biological products 2.107clean areas 2.100–101enclosed areas 2.60
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appeals procedures, GMPinspectorate 2.189–190
applicants, WHO CertificationScheme 1.205
application, definition 2.139asbestos-containing filters 2.98aseptic procedures 2.91, 2.97–98assay procedures 1.118, 1.126, 1.128,
1.168assessment 1.3–6
herbal medicines 1.4, 1.31–37multisource products 1.66–69new products 1.21, 1.26pre-marketing 1.112–113safety 1.25, 1.29, 1.34–35see also quality assessment
attenuated total reflectance (ATR)1.141–142
authorization 1.216, 1.217clinical trials 1.21–22narcotic/psychotropic substances
1.218–219new product licences 1.26pre-marketing assessment 1.112
authorization holders, list 2.189authorized person 2.11, 2.27, 2.177
definition 2.11, 2.177role and functions 2.3
autoclaves 2.95, 2.133automated process controls and
processing equipment 2.69available samples, definition 1.178
Bacillus anthracis 2.107basic tests 1.9–10, 1.111, 1.150–153
objectives 1.150recommended methods 1.151–153
batchdefinitions 1.48, 1.179, 1.205, 2.11,
2.160numbering 1.205test sampling 1.52–53
batch certificates 1.114, 1.190, 1.192,1.205
imported drugs 1.213model 1.202–204
batch control see batch certificatesbatch documentation, GMP 2.62–63batch number, definitions 2.11, 2.161batch records
definition 2.11excipients 2.76–77
GMP 2.44–46review 2.56
batch size, for investigationalproducts 2.121
bioavailability 1.30, 1.64, 1.107multisource products 1.67–68, 1.69product non-approval 1.84–85
“biobatch” production 2.68bioequivalence 1.30, 1.64–65, 2.68bioequivalence studies 1.74–80
marketing authorization 1.69–70metabolite data 1.78results reporting 1.80statistics 1.79–80, 1.104symbols used 1.103
biological control training programme1.16, 1.229, 1.234–235
biological indicators 2.94, 2.97biological preparations
distribution and processing records2.110–111
quality assurance/quality control2.111–112
biological processes, inherentvariability 2.104
biological productsGMP 2.3–4, 2.103–113in-process controls 2.111labelling 2.109–110premises and equipment 2.105–108WHO recommendations 1.107
biological reference standards seereference standards
biological substances, containers 2.107biological tissues, extraction of
substances 2.103blending/mixing, in-process 2.79–80blinding operations, investigational
products 2.123blood or plasma derivatives 2.103, 2.105,
2.107, 2.133British Standards Institution (BS 5750)
2.146buildings see premisesbulk drug substances see active
pharmaceutical ingredientsbulk products 1.206
assessment 2.123definition 2.11GMP 2.37instruments 1.127, 1.173quality control 2.54
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sampling 1.176specifications 2.41
calibration, definition 2.11calorimetry, differential scanning 1.129campaign manufacture 2.106, 2.107Canada, in vivo equivalence study
requirements 1.89–102, 1.89carcinogenicity, herbal substances 1.29,
1.33cell banks, storage 2.106Certificate of a Pharmaceutical Product
see product certificatescertificates 2.112, 2.137
of analysis 1.169reference substances 1.134WHO Certification Scheme 1.190–
204, 1.195–197, 1.200–201, 1.202–204
see also product certificatesCertification Scheme on the Quality of
Pharmaceutical Products Movingin International Commerce (WHOCertification Scheme) 1.1, 1.3,1.7, 1.12–14, 1.27, 1.30, 1.143,1.148, 1.178, 1.187–219, 2.2, 2.4,2.9–10
abuse of scheme 1.194certificate 1.190–204, 1.195–197,
1.200–201, 1.202–204certifying authorities 1.206counterfeit products 1.223glossary and index 1.204–209herbal medicines 1.34implementation guidelines 1.187–219imported drugs 1.107, 1.114, 1.210–
211multisource products 1.66objectives 1.187–188participation eligibility 1.188–189WHO responsibility 1.194, 1.209
changescontrol, for excipients 2.77–78post-marketing 1.85revalidation after 1.112significant 2.150
changing see clothingcharges, product certificates 1.191checklist
for inspection and preparation ofreport 2.169–173
for inspectors 2.150
chemical control training programme1.228, 1.231–232
chemical reference standards see referencestandards
chemical reference substances seereference substances
chiral drug substances 1.78chromatography 1.125, 1.130
equipment 2.109, 2.134training 1.232see also gas-liquid chromatography;
thin-layer chromatographyclean areas
airborne particulate classificationsystems 2.90
classification 2.88–89definition 2.11personnel 2.98–100, 2.104–105,
2.131premises 2.100–101sanitation 2.87–88sinks 2.106, 2.132for sterile preparations 2.86working conditions 2.106working practices 2.92, 2.105,
2.131cleaning, of premises 2.30cleaning limits, residual materials 2.73cleaning procedures
investigational products 2.118multipurpose equipment 2.72–73validated 2.61written 2.73
cleanliness see hygiene; personal hygieneclimatic zones 1.38, 1.47–48, 1.51–53,
1.51–52, 1.53clinical trials 1.72–74, 1.73–74, 2.4
authorization 1.21–22complaints 2.117definition 2.114–115equivalence testing 1.70, 1.72,
1.82on pharmaceutical products
2.113–124protocols 1.74reference products 2.118selection of an appropriate dosage
2.114clinics, inspection 2.167, 2.173“closed” systems 2.133Clostridium botulinum 2.107Clostridium tetani 2.107
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clothingchanging facilities 2.60, 2.99, 2.100disposable 2.99laundering or cleaning 2.99outdoor 2.99personnel 2.61protective 1.174, 2.61, 2.99
coding systems, investigational products2.121
combination products 1.29, 1.36commingling, definition 2.70company documents 2.149competence, national authorities 1.189competent authorities, WHO
Certification Scheme 1.206complaints 2.19–20
dealing with 2.66excipients 2.71GMP 2.191, 2.196investigational products 2.117procedures 2.171records 2.149sampling 1.181in site master file 2.157spot checks 2.148
component failures 2.211computer systems
audit 2.85in control of manufacturing
processes 2.76–77WHO drug registration package 1.3
concentrations, tests for 1.123–124,1.123
conditions for sale and supply, inspection2.171
Conference of Experts on the RationalUse of Drugs, Nairobi (1985) 1.1,1.15, 1.38, 2.1
confidentiality 2.188–189confusion 2.17consignments
acceptance sampling 1.182–186definitions 1.179, 2.12
constituents with known therapeuticactivity, definition 2.125
consumers, counterfeit products1.225–226
containersbiological substances 2.107effects on stability 2.83–84specifications 2.76sterile products 2.102
contaminationdefinition 2.12microbiological 1.119prevention during production 2.49–50samples 1.179tests for 1.129–131see also cross-contamination
continuous culture 2.112contract 2.22–23
accepter 2.22giver 2.21–22production and analysis 2.21–2.23,
2.157, 2.196control, definition 2.202control measure, definition 2.202controlled drugs 2.167
definition 2.161diversion 2.171
Convention for the Mutual Recognitionof Inspection in Respect of theManufacture of PharmaceuticalProducts 1.188
Convention on Psychotropic Substances(1971) 1.217, 1.218, 1.219
conveyor belt, in clean area 2.101cooperation between firms 2.59corrective action 2.204, 2.208–209
definition 2.202cosmetics 2.99counterfeit products 1.1, 1.15,
1.220–226, 2.5, 2.20definitions 1.216, 1.220, 2.161imported 1.214recommendations 1.222–226
Counterfeiting Intelligence Bureau,International Chamber ofCommerce 1.221
critical control point (CCP) 2.203–204definition 2.202determination 2.207–208
critical limits 2.203definition 2.202specification and verification
2.207–208critical operation, definition 2.12cross-contamination 2.17, 2.30
avoidance/prevention 2.32, 2.33,2.49–50, 2.78, 2.107
definition 2.12see also contamination
crude plant materials 1.33definition 2.125
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culture media, GMP 2.38customs
counterfeit products 1.223, 1.224imported drugs 1.211–215, 1.217–219storage facilities 1.215
cytokines 2.103cytostatic substances, enclosed areas 2.60
datapresentation, analytical procedures
1.120verification 2.142
date of manufacture 1.43decontamination systems 2.107defective products 2.19–20
WHO Certification Scheme 1.194defects, dealing with 2.66defined storage instructions 1.43degradation
basic tests 1.150–151during transit 1.107reference substances 1.133stability testing 1.4–6see also deterioration
delivery, definition 2.12design
bioequivalence studies 1.76–77, 1.103stability studies 1.51, 1.52–54
design qualification (DQ) 2.19destruction, of unused investigational
products 2.124detection, limit of 1.122, 1.123detergents 2.87deterioration
drug products 1.39–40inadequate storage 1.38see also degradation
developing countriescounterfeit products 1.224drug analysis training programme
1.227–235drug control 1.2–3, 1.18–30drug production 1.13health budgets 1.1The international pharmacopoeia 1.7–8national laboratories 1.10–12,
1.154–162training fellowships 1.235–238
developmentbasic tests 1.151–153laboratory services 1.162see also product development
deviation, definition 2.202diagnostic agents for in vitro use 2.103differential scanning calorimetry 1.129diffuse reflectance techniques 1.142disinfectants 2.87distribution 1.7, 1.105–115
channels 2.5, 2.157–176drug stability 1.4–5inspection 2.5, 2.157–176, 2.160–163,
2.167packaging and storage 1.107quality surveillance 1.114–115records
biological preparations 2.110–111radiopharmaceuticals 2.136
reference substances 1.135in site master file 2.157
distributorscounterfeit products 1.224licences 1.21responsibilities 1.107
documentationanalytical 2.144on company to be inspected 2.149excipient manufacture 2.75–77GMP 2.40–48, 2.61–63, 2.182–183,
2.196HACCP 2.210herbal medicines 2.126–128imported products 1.213investigational products 2.119–121licensing 1.27multisource products 1.68–69reference substances 1.133–134in site master file 2.157therapeutic equivalence 1.69–70, 1.71WHO Certification Scheme
1.190–204, 1.195–197, 1.200–201,1.202–203
dosage forms 1.65, 1.206bioavailability 1.64in clinical trials 2.114, 2.116drug degradation 1.4equivalence studies 1.88, 1.89–102equivalent 2.143The international pharmacopoeia
1.117–119, 1.127quality specifications 1.110–111sampling 1.182–183solid oral 2.143stability 1.4–5, 1.37–46
deterioration factors 1.39–40
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less stable substances 1.44–45testing guidelines 1.46–56testing training 1.232verification 1.153
drainage 2.33see also sinks and drains
drug analysis, training programmes1.227–235
drug control agencies 1.108, 1.109–110drug control laboratories 1.154–174
instruments and their calibration1.172–173
organizational structure 1.164reagents 1.170–172reference materials 1.172safety 1.173–174samples handling 1.165–169specifications repertory 1.170staffing 1.164–165, 1.227training programme 1.227–235see also laboratory services
drug control systems 1.1, 1.18–30government agencies 1.108,
1.109–110government laboratories 1.162–174imported drugs 1.211, 1.212–214,
1.217–219national 1.106national laboratories 1.154–162provisional registration 1.24–25see also regulation; regulatory
authoritiesdrug distribution see distributiondrug inspector see inspectordrug legislation see legislationdrug master file, definition 2.70drug regulatory authorities see regulatory
authoritiesdrug substance, physical characteristics
and specifications 2.143drugs
classification 2.160definitions 1.106, 2.161nomenclature 1.113side-effects and toxicity 2.160
eating, drinking, and smoking facilities 2,61, 2.60
educationcounterfeit products 1.225–226patients 1.42see also qualifications; training
efficacydrugs 1.106–107herbal medicines 1.35–36
electronic data-processing systems 2.62–63
see also computer systemseligibility, WHO Certification Scheme
1.188–189enclosed areas, for special purposes 2.60endotoxin/pyrogen free see sterileendotoxins, monitoring 2.109environmental hazards 2.211environmental monitoring 2.117enzymes 2.103equipment
biological products 2.105–108calibration 1.127, 1.172–173, 2.61for chromatography 2.109, 2.134clean areas 2.101–102cleaning and maintenance 2.60, 2.61,
2.72critical 2.134defective 2.61excipients 2.72–73GMP 2.34, 2.60–61, 2.195investigational products 2.117–118maintenance record 2.77multipurpose 2.60, 2.72, 2.73national laboratories 1.156, 1.156,
1.158–160, 1.159new or changed 2.143, 2.150radiopharmaceuticals 2.132–133sampling procedures 1.179–180in site master file 2.156
equivalence, pharmaceutical 1.66equivalence studies
clinical interchangeability 1.67–68marketing authorization 1.69–72national requirements 1.88–102,
1.89–102types of 1.72–83when not necessary 1.70–71see also interchangeability
errors, human and organizational2.212
escort, for inspector 2.149, 2.151essential drugs 1.1, 1.58–60established ingredients, product licensing
1.27–28ethics, clinical trials 1.73ethylene oxide 2.96eukaryotic cells, growth of strains 2.103
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European Community, stability testingguidelines 1.57
European Organization for QualityControl, stability testingguidelines 1.57
European Standard EN 45012 2.177evaluation
reference substances 1.127–131stability testing 1.54test results 1.169
examplesinspection report 2.6Model Batch Certificate of a
Pharmaceutical Product1.202–204
Model Certificate of GoodManufacturing Practices2.197–199
Model Certificate of a PharmaceuticalProduct 1.195–199
Model Essential Drugs stability surveyanswer sheet 1.58–60
Model Statement of Licensing Statusof Pharmaceutical Products1.200–201
receipt form 2.175–176stability testing summary sheet 1.61stability testing survey answer sheets
1.58–60excipient manufacture
ISO 900 series certification 2.69water systems/water quality 2.81–82
excipient manufacturerinspection 2.71–72responsibilities 2.68–70
excipientsbatch production records 2.76–77definition 2.71delivery 2.82documentation 2.75–77equipment 2.72–73expiry dates 2.84GMP 2.66–85good production practices 2.78–82importance 2.67–68packaging operations 2.82processing steps 2.69quality control 2.82–85retention samples 2.83returned 2.75specifications 2.76stability studies 2.83–84
sterile 2.71, 2.80–81storage 2.75
Expert CommitteesBiological Standardization 1.107–108,
1.158, 2.3, 2.104Essential Drugs 1.2Nonproprietary Names 1.113Specifications for Pharmaceutical
Preparations 1.1–12, 1.14–15,1.38, 2.1–2, 2.3, 2.4, 2.5, 2.9,2.177
basic tests 1.150laboratory services 1.154–155,
1.227–228quality assurance 1.105–106, 1.110,
1.111expired stock see time-expired stockexpiry dates 1.4, 1.5, 1.42, 1.48
drug stability 1.38–39excipients 2.84labelling 1.115reference substances 1.134time-expired stock 1.40
explosions 2.211export authorization, narcotic/
psychotropic substances1.218–219
exported products, WHO CertificationScheme 1.20, 1.189, 1.190–191
exporting countries, responsibilities,multisource products 1.66, 1.67
face mask 2.99facilities, new or changed 2.143, 2.148,
2.150failures, common 2.211–212feasibility studies, national laboratories
1.161–162fellowships, IFPMA quality control
training 1.235–238fermentation products 2.103fibres, shedding 2.92, 2.98, 2.99final samples, definition 1.178finished products
assessment 2.123definitions 1.206, 2.12, 2.161GMP 2.37herbal medicines 1.34quality control 2.54specifications 2.43stability 1.39, 1.40, 1.46–56test records 2.55
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fires 2.211first-stage national laboratory 1.155–156,
1.156fixed-ratio combination products 1.29flow diagram 2.201, 2.202, 2.206follow-up
regulatory/administrative decisions2.144–145
visits 2.148Food and Drug Administration (USA),
stability testing guidelines 1.57formulations
drug stability 1.40, 1.47major modifications 1.50
Fourier transform infrared spectrometers(FTIRs) 1.137
freeze drying 2.134frequency, of product testing 1.54frequency scale, infrared
spectrophotometry 1.137FTIRs see Fourier transform infrared
spectrometers
gas-liquid chromatography (GLC) 1.118,1.130, 1.131
see also chromatography; thin-layerchromatography (TLC)
General Agreement on Tariffs and Trade(GATT), counterfeiting 1.222
generic products 1.29–30, 1.75definition 1.65interchangeability 1.6, 1.30procurement 1.3see also multisource products
genetic phenotyping 1.75Germany
in vivo equivalence study requirements1.89–102, 1.89
legal status of investigational products2.113
stability guidelines 1.57global workshops, counterfeit drugs 1.15glossaries
distribution channel inspection 2.160–163
drug stability 1.42–44, 1.48–49excipients 2.70–71GMP 2.10–15HACCP 2.202–203herbal medicines 2.125–129import procedures 1.216–217inspectorate 2.160–163
investigational products 2.114–115multisource products 1.64–66pre-approval inspections 2.139–140quality system requirements 2.177–178sampling 1.177–179WHO Certification Scheme 1.204–209
gloves 2.99see also protective clothing
GLP see good laboratory practice (GLP)GMP see good manufacturing practice
(GMP)good clinical practice (GCP) 2.16, 2.113,
2.202good laboratory practice (GLP) 1.162–
174, 2.16, 2.202good manufacturing practice (GMP) 1.6,
1.111–112, 1.187–188compliance 2.59, 2.139, 2.142, 2.145,
2.147definition 2.161and HACCP 2.201–202inspection report guidance 2.193–199inspectorate see inspectorateinterchangeability 1.63, 1.66model certificate 2.6, 2.197–199non-compliance 2.147, 2.150, 2.152,
2.153for pharmaceutical products 2.17–18,
2.158–159starting materials 2.58–85status 2.9web page 2.9WHO Certification Scheme 1.190WHO guidelines 2.2–4
good pharmacy practice 1.7definition 2.161
government inspectorate see inspectorategovernments
counterfeiting 1.222drug control agencies 1.109–110drug control laboratories 1.110, 1.162–
174drugs budgets 1.1
gravimetric methods, training 1.231guidance
counterfeit products 1.220–226The international pharmacopoeia
monograph preparation 1.116–119
guidelinesanalytical validation 1.119–124basic tests 1.150–153
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chemical reference substances 1.124–136
GLP, drug control laboratories1.11–12, 1.162–174
GMP 1.6herbal medicines assessment 1.4,
1.31–37import procedures 1.14, 1.210–215infrared spectrophotometry (general
recommendations) 1.136–149multisource product interchangeability
1.6, 1.62–104national laboratories 1.154–162quality assurance in supply systems
1.105–115sampling procedures 1.12, 1.175–186stability of drug dosage forms 1.37–46stability testing 1.4–5, 1.46–61WHO Certification Scheme 1.13–14,
1.187–210guiding principles, small national drug
regulatory authorities 1.2–3,1.18–30
HACCP see hazard analysis and criticalcontrol point (HACCP)
hair, covering 2.99handling procedures
drug stability 1.41reference substances 1.131–134
hazarddefinition 2.203examples 2.210–211
hazard analysis 2.6, 2.10, 2.203,2.206–207
definition 2.203hazard analysis and critical control point
(HACCP)documentation and record keeping
2.210glossary 2.202methodology 2.6, 2.200–212plan 2.203system, guidelines 2.204team 2.205training and education 2.204–205verification procedures 2.209–210
hazardous chemicals 2.200, 2.210hazardous waste 2.211headgear 2.99health care professionals, counterfeit
products 1.224
health monitoring, test subjects 1.75heavy metals, tests for 1.118HEPA filters see high-efficiency
particulate air (HEPA) filtershepatitis B vaccination 2.105herbal medicines 1.31
assessment 1.4, 1.31–37combination products 1.36definitions 2.125documentation 2.126–128efficacy assessment 1.35–36finished product specifications 2.128GMP 2.4, 2.125–129licensing 1.25long-term use 1.32–33, 1.34, 1.35premises 2.126processing instructions 2.128quality assessment 1.33–34quality control 2.129safety assessment 1.25, 1.29, 1.34–35stability tests 2.129starting materials 2.126–127toxicological studies 1.34
herbicides 2.78high-efficiency particulate air (HEPA)
filters 2.89, 2.95high-performance liquid chromatography
(HPLC) 1.118, 1.130homogeneity
basic tests 1.151–153definition 1.176
hormones 2.60, 2.103hospital radiopharmacies 2.130hospitals, inspection 2.167HPLC see high-performance liquid
chromatographyhumidity
infrared spectrophotometry 1.138protection of instruments 1.172–173storage 1.132
hybridoma techniques 2.103hydrogen peroxide vapour 2.96hygiene 2.18, 2.60, 2.61, 2.196
see also personal hygiene
ICRS see International ChemicalReference Substances
identity testing 1.123–124, 1.123,1.150
infrared spectrophotometry 1.128,1.140–141
reference substances 1.127, 1.128
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IFPMA see International Federation ofPharmaceutical ManufacturersAssociations
immune sera 2.103immunoglobulins 2.103implementation, control laboratory
projects 1.161–162import authorities, definition 1.216import controls 1.211, 1.212–214,
1.217–219importation 1.14, 1.210–219
definition 1.216imported products
consignment sampling 1.182exporting country responsibilities 1.66,
1.67generic 1.30guidelines on procedures 1.210–215herbal medicines 1.34legislation 1.211–213port of entry procedures 1.114–115quality assessment 1.107, 1.108quality surveillance 1.114stability 1.4, 1.38WHO certification scheme 1.107,
1.114, 1.189, 1.190–191importers
definition 1.216guidelines for agents 1.190inspection 2.172notifiable medicinal products 1.24responsibilities 1.107
impuritiesdosage forms 1.117–118tests for 1.123–124, 1.123, 1.129–131see also contamination; cross-
contaminationin vitro dissolution studies 1.70, 1.72,
1.82–84in vivo studies
national requirements 1.88–102,1.89–102
therapeutic equivalence 1.67–68,1.71–72, 1.74–82
in-process blending/mixing 2.79–80in-process control
biological products 2.111definition 2.12records 2.55
in-process testing, quality control2.82
independent analysis, samples 1.14
industrially manufacturedpharmaceuticals, samplingprocedures 1.12, 1.175–186
informationreference substances 1.133–134see also product information
information exchangecounterfeit products 1.221, 1.223multisource products 1.66national regulatory authorities 1.19,
1.66, 1.69reference substances 1.136
information sourcesclinical trials 1.22drug registration software 1.3good pharmacy practices 1.7laboratory equipment 1.11manufacturers 1.132narcotic/psychotropic substances 1.218nonproprietary names 1.113quality assurance 1.2, 1.9reference substances 1.9UN 1.218WHO Certification Scheme 1.14,
1.189, 1.190infrared reference spectra 1.9, 1.141,
1.148–149, 1.149infrared spectrophotometry 1.117,
1.125–127, 1.131apparatus 1.137environment 1.138frequency scale 1.137general recommendations 1.136–149identification by 1.140–141list of available reference spectra
1.148–149reflectance techniques 1.141–142solvents use 1.138substance preparation 1.138–140see also spectrophotometry; ultraviolet
spectrophotometryinjectable products, testing 2.87INN see International Nonproprietary
Nameinnovator products 1.65insecticides 2.78inspection 2.139–199
announced 2.149, 2.165by an external body or person 2.186,
2.187comprehensive 2.165concise 2.147, 2.149, 2.166
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of counterfeit, spurious or substandardproducts 2.174–175
of distribution channels 2.5, 2.157–176facilities required 2.186follow-up 2.148, 2.149, 2.166frequency and duration 2.148–149,
2.166government control laboratories 1.163investigative 2.166of manufacturing and quality control
facilities 2.4–5methods 2.165–166of pharmaceutical manufacturers
2.145–157of premises 2.170preparing for 2.149procedures 2.149–151, 2.184–186process 2.147–154quality systems principles 2.5routine 2.147, 2.149, 2.165sampling during 1.181, 2.151skills required 2.159SOPs 2.167special 2.148, 2.149, 2.166team, composition 2.71, 2.141types 2.169unannounced 2.149, 2.166visual records 2.151see also self-inspection
inspection reports 2.149, 2.152, 2.185–186
exchange between countries 2.188form and content 2.154–157guidance on 2.193–199model lay-out 2.6
inspectoraccess to premises, documents, or
information 2.151in national drug regulatory authorities
2.159qualifications 2.163–164reference/information sources 2.166role 2.146–147, 2.149training material 2.10use of checklists 2.150
inspectorateappeals procedures 2.189–190complaints procedures 2.191documentation 2.182–183follow-up regulatory/administrative
decisions 2.144–145functions 1.109
government body 2.146impartiality 2.178mutual recognition 2.177organizational structure 2.178, 2.179–
181personnel 2.181–182
see also inspectorpowers 2.186publications 2.189recalls and withdrawals procedure
2.191recommended procedure 2.178–179records 2.183–184role and functions 2.160, 2.163–164terms of reference 2.179
installation qualification (IQ) 2.19instructions, storage conditions 1.43instruments 1.172–173
analysis training programme 1.228calibration 1.127, 1.172–173national laboratories 1.158–160,
1.159intellectual property rights
counterfeiting 1.221, 1.222interchangeable products 1.64
interchangeabilitymultisource products 1.6, 1.30, 1.62–
104see also equivalence studies
intermediate productsdefinition 2.12GMP 2.37, 2.63quality control 2.54specifications 2.41
internal audit 2.145, 2.146GMP inspectorate 2.190–191reports 2.149
International Atomic Energy Agency(IAEA) 2.4
International Chamber of Commerce,Counterfeiting IntelligenceBureau 1.221
International Chemical ReferenceSubstances (ICRS) 1.9,1.135–136, 1.142–148,1.143–148
International Conference of DrugRegulatory Authorities(ICDRA) 1.32, 1.63
International Conference onHarmonisation, stability testingguidelines 1.58
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International Conference on PrimaryHealth Care, Alma-Ata(1978) 1.1, 1.32, 2.1
International Federation ofPharmaceutical ManufacturersAssociations (IFPMA) 1.224
fellowships 1.235–238International Infrared Reference
Spectra 1.9, 1.141, 1.148–149,1.149
International Narcotics Control Board(INCB) 1.218, 1.221–222
international narcotics rings, medicinecounterfeiting links 1.221–222
International Nonproprietary Name(INN) 1.113, 2.10
International Organization forStandardization (ISO), 9000 seriesstandards 2.5, 2.67, 2.69, 2.89,2.146, 2.177
International Pharmaceutical Federation1.7
The international pharmacopoeia 1.2,1.7–9, 1.116–149, 2.1, 2.2, 2.9
international trade, pharmaceuticals1.12–14, 1.187–219
intrinsic thermodynamic properties,analytical methods 1.129
investigational products 2.113–124batch records 2.121batch size 2.121–122blinding operations 2.123cleaning procedures 2.118coding (randomization) systems
2.121definition 2.115documentation 2.119–121GMP 2.4, 2.113–114inspection procedures 2.142labelling instructions 2.120–121manufacturing operations 2.122master formulae 2.120packaging and labelling 2.120, 2.122premises and equipment 2.117–118processing instructions 2.120production 2.121–123quality assurance 2.116quality control 2.123specifications 2.119–120starting materials 2.118unused 2.123
investigator, definition 2.115
irradiation 2.95–96ISO see International Organization for
Standardization
Japan, stability testing guidelines 1.58jewellery 2.99job descriptions 2.25
kits, for radiopharmaceuticals 2.130,2.135, 2.136
labellingbiological products 2.109–110correct 2.64evaluation of control procedures 2.142expiry dates 1.115GMP 2.41herbal medicines 1.36inspection 2.172investigational products 2.120–121,
2.122radiopharmaceuticals 2.134–136reference substances 1.133–134samples 1.166, 1.180–181see also packaging
laboratory equipment and procedures,evaluation 2.143
laboratory services 1.10–12, 1.154–186,1.156, 1.159
equipment prices 1.11good practice guidelines 1.11–12,
1.162–174quality control 1.110safety 1.173–174, 1.179–180see also drug control laboratories;
national laboratoriesstaffing 1.155–156, 1.158, 1.162,
1.164–165large-volume infusion solutions, testing
2.87large-volume parenterals, definition 2.12legislation
counterfeit products 1.222, 1.224imported drugs 1.211–213purpose 2.159, 2.160quality assurance 1.108regulatory authorities 1.22–23
less stable substances 1.44–45, 1.53licence-holders 1.27, 1.207licences 1.20–21, 1.26–27, 1.216, 1.217licensing 1.3, 1.19–30, 1.187
application 2.139
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developed countries 1.160established products 1.27–28exemptions 1.20generic products 1.30, 1.66inspection 2.169manufacturers/distributors 1.21multisource products 1.30, 1.66new products 1.26, 1.28Statement of Status 1.190, 1.192Summary Basis of Approval 1.209
licensing authoritiesfunctions 1.19–20technical competence 1.23
limit of detection, analytical procedures1.122, 1.123
limit of quantitation, analytical procedures1.122–123, 1.123
limits of certificate by competentauthority 1.191, 1.193
linearity, analytical procedures 1.121–122, 1.123
live organisms, handling 2.106long-term stability studies 1.48long-term use, herbal medicines 1.32–33,
1.34, 1.35lot see batch
manufactureauthorization 2.139, 2.141definitions 1.207, 2.12, 2.140equipment see equipmentGMP 1.6, 1.108, 1.111–112investigational products 2.122licence 2.149new products 2.143process evaluation 2.142quality surveillance 1.113–114see also good manufacturing practices
(GMP)manufacturer
counterfeit products 1.221, 1.224definitions 1.207, 2.12, 2.140inspection 2.145–157licensed 2.9licensing 1.21multisource products 1.64notifiable medicinal products 1.24quality control function 2.52responsibilities 1.107
drug stability 1.4–5, 1.41, 1.50responsibility 2.17, 2.59sampling plans 1.184
of starting materials, identification2.143
weak points 2.150markers, definition 2.125marketing
pre-marketing assessment 1.112–113surveillance during 1.113–115, 1.182
marketing authorization 2.5, 2.9, 2.149,2.158
definition 2.13equivalence studies 1.63, 1.69–72multisource products 1.66, 1.68–69see also product licencestechnical data 1.68–69
master formuladefinition 2.13documentation 2.43GMP 2.61–62investigational products 2.120
master record, definition 2.13materials
excipients 2.73–75GMP 2.35–39, 2.195see also starting materials
maternity homes, inspection 2.173mean climatic conditions 1.51–52, 1.51,
1.52mean kinetic temperature 1.48, 1.51measuring and test equipment,
calibration 2.84–85media, sterilization 2.109medicinal plant material
definition 2.125description 2.127
medicinal plants 1.31–33definition 2.125see also herbal medicines
medium-size national laboratory 1.157–160
capability 1.157equipment 1.158–160, 1.159scope of activity 1.160–161staffing 1.158
Member States, WHO CertificationScheme 1.14, 1.188–189
metabolite data, bioequivalence studies1.78
method validation/verificationdefinition 2.140report 2.144
microbiological contamination 1.119clean areas 2.88
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control 2.80–81limits 2.88monitoring 2.109
microbiological control trainingprogramme 1.16, 1.228, 1.229,1.232–234
IFPMA fellowships 1.235, 1.237microbiological testing 1.158microorganisms
growth of strains 2.103live 2.91propagation 2.103survival or multiplication 2.207
model productapproach to stability assessment
2.83–84definition 2.70
models see examplesmoisture content, reference substances
1.131, 1.133monitor, definitions 2.115, 2.203monitoring
analytical 1.119–124basic tests programme 1.153for CCPs 2.208reference substances 1.132–133
monkeys 2.108monoclonal antibodies 2.103monographs
data presentation 1.120The international pharmacopoeia
1.116–119mother liquor
definition 2.70reuse 2.78–79
multi-use areas 2.78multisource products
definition 1.65equivalence studies 1.69–83interchangeability 1.6, 1.62–104marketing authorization 1.69–72registration 1.62–104regulatory assessment 1.66–69see also generic products
“n plan”, consignment sampling 1.185,1.186
narcotics 1.221import controls 1.211, 1.217–
219medicine counterfeiting links 1.221–
222
national drug regulation 1.2–3, 1.18–30,1.105–115
see also regulatory authoritiesnational laboratories 1.10–11,
1.154–162feasibility studies 1.161–162first-stage 1.155–156, 1.156good laboratory practices 1.162–174medium-size 1.157–160, 1.159organization and staffing 1.155–161,
1.162, 1.164–165project implementation 1.161–162see also drug control laboratoriessize/location 1.161specifications repertory 1.170staffing 1.155–156, 1.158, 1.162,
1.164–165national requirements
GMP inspectorates quality systems2.176–192
in vivo equivalence studies 1.88–102,1.89–102
natural forces 2.212new chemical entities 1.3, 1.28new products
assessment 1.21, 1.26licensing 1.26manufacture 2.143nonproprietary names 1.113tropical parasitic diseases 1.28
nomenclature, standardization 1.113noncommercial institutions, quality
systems principles 2.177nonproprietary names 1.113normal storage conditions 1.43notification, pre-marketing assessment
1.112nuclear centres and institutes 2.130,
2.131nursing homes, inspection 2.173nutrient medium 2.92
objectivesbasic tests 1.150drug analysis training programme
1.228The international pharmacopoeia 1.116stability testing 1.49, 1.49–50WHO Certification Scheme 1.187–
188operating conditions, deviations from
normal 2.211
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operational qualification (OQ) 2.19optical rotation methods 1.131order
definition 2.116investigational products 2.119
organizationGMP 2.194government control laboratories 1.164
organizational chart 2.25, 2.59, 2.155GMP inspectorate 2.180
original samples, definition 1.178“other” ingredients, in medicinal plant
materials 2.128over-the-counter drugs 2.160
definition 2.162
“p plan”, consignment sampling 1.185,1.186
package insert 2.110packaging
batch records, investigational products2.121
control procedures, evaluation 2.142definition 2.13drug stability 1.40, 1.47excipients 2.82GMP 2.44, 2.51–52, 2.64herbal medicines 1.36instructions
GMP 2.44investigational products 2.120
investigational products 2.122product information 1.133–134quality assurance 1.107samples 1.180–181see also labelling
packaging materialsdefinition 2.13GMP 2.36–37specifications 2.41storage 2.32test requirements 2.55
packing, reference substances 1.131–132parallel market, definition 2.163participation, WHO Certification
Scheme 1.13, 1.188–189patients, education 1.42performance qualification (PQ) 2.19periodic review, GMP inspectorate
2.190–191personal hygiene 2.29–30, 2.98
see also hygiene
personnelbiological products manufacture
2.104–105changes 2.150in clean areas 2.98–100, 2.104–105,
2.131clothing see clothingdrug analysis training programme
1.227–235GMP 2.59–60, 2.194health checks/health status 2.60, 2.61,
2.98, 2.104, 2.131human and organizational errors
2.212hygiene 2.61inspection 2.17investigational products 2.117key 2.26–28laboratories 1.155–156, 1.158, 1.162,
1.164–165, 1.227qualifications and responsibilities
2.25–28quality surveillance 1.109safety 2.6, 2.10, 2.211sampling procedures 1.179in site master file 2.155–156training and education in HACCP
2.204–205training and expertise 2.25, 2.28–29,
2.59–60, 2.105, 2.132, 2.181–182training material 2.10unauthorized/untrained 2.25, 2.29,
2.30vaccination 2.105
pesticides 2.78pharmaceutical equivalence see
equivalencepharmaceutical excipients see excipientsPharmaceutical Inspection Convention
(PIC) 1.58, 2.177pharmaceutical inspector see inspectorpharmaceutical products
counterfeit/spurious/substandard2.160, 2.167, 2.174–175
definitions 1.207, 1.216, 2.13, 2.116,2.161
HACCP methodology 2.200–212hazard and risk analysis 2.200–212licensed 2.9moving in international commerce
2.167see also drugs
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pharmaceuticalsdefinition 2.203see also drugs
pharmacieshospital 2.172–173inspection 2.167, 2.172–173retail 2.159, 2.172–173wholesale outlets 2.159
pharmacistdefinition 2.162responsibilities 1.7, 1.17, 1.42,
1.225pharmacodynamic studies 1.70, 1.72,
1.80–81pharmacognostic testing, training 1.232pharmacokinetic abbreviations 1.103pharmacopoeias 1.110, 1.170
The international pharmacopoeia 1.2,1.7–9, 1.116–149
monographs 1.10, 1.116–119, 1.150pharmacy-only drugs 2.160
definition 2.162phase solubility analysis 1.129photographs or videos, taken during
inspection visit 2.151physical tests, training 1.231pipework 2.33, 2.34, 2.108plant preparations 1.33, 2.127–128
definition 2.125poisons 1.170–171
definition 2.162pollution, prevention 2.10pooled samples, definition 1.178ports and stores, inspection 2.167positive pressure areas 2.107, 2.133positron emission tomography (PET)
centres 2.130, 2.131post-marketing
product change 1.85surveillance 2.185
potentiometric techniques, training1.231
powers of enforcement, regulatoryauthorities 1.22–23
pre-approval batches 2.141definition 2.140
pre-approval inspections 2.139–145,2.142
pre-marketing quality assessment1.112–113
precision, analytical procedures 1.121,1.123
premisesbiological products 2.105–108clean areas 2.100–101GMP 2.30–33, 2.60, 2.194–195herbal medicines 2.126inspection 2.170investigational products 2.117–118national laboratories 1.156, 1.157–158radiopharmaceuticals 2.132–133in site master file 2.156validated cleaning procedures 2.61
prescription-only drugs 2.160definition 2.162
presentation, analytical procedures data1.120
priority planning, provisionally registeredproducts 1.25
process, full description for HACCP2.205–206
process validation 2.19excipients 2.77–78
process-monitoring systems 2.61processing, sterile preparations 2.91–93processing instructions, investigational
products 2.120processing procedures, GMP 2.50–51,
2.63processing records
biological preparations 2.110–111investigational products 2.121
procurementagencies’ responsibilities 1.42generic products 1.29–30public sector 1.3registered products 1.13
productassessment see assessmentchanges 2.150full description for HACCP
2.205–206new 1.21, 1.26, 1.28, 1.113, 2.143recall see recalltesting 2.185
product certificates 1.190–191, 1.195–197, 1.195–199, 1.207–208
product developmentin vitro dissolution tests 1.83–84stability testing 1.50
product informationherbal medicines 1.36–37multisource products 1.69WHO Certification Scheme 1.208
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product licences 1.20–21, 1.26, 1.208see also marketing authorization
product specification file(s)definition 2.116investigational products 2.119
production 1.208biological products 2.108–109definition 2.13GMP 2.48–52, 2.63–66investigational products 2.121–123radiopharmaceuticals 2.133–134in site master file 2.157
production areasGMP 2.32–33herbal medicines 2.126
production practices, GMP 2.195production processes, validation
2.116production records,
radiopharmaceuticals 2.136production sites, inspection 2.167prohibited drugs 2.160
definition 2.162promotion
compliance with drug laws 2.171herbal medicines 1.37laboratories 1.174multisource products 1.69
protective clothing 1.174, 2.61, 2.99protocols
clinical trials 1.74definition 2.116
provisional registration 1.24–25existing medicinal products 1.24herbal medicines 1.29product screening 1.24–25
provisional shelf-life 1.43, 1.44psychotropic substances 1.221
import controls 1.211, 1.217–219public disclosure, quality specifications
1.110–111public sector, procurement 1.3publications, GMP inspectorate 2.189purity
procurement, reference substances1.127, 1.128, 1.129–131
see also contamination; cross-contamination
qualifications 2.18–19definition 2.14IFPMA training fellowships 1.237–238
laboratory staff 1.156, 1.158, 1.162,1.164–165
see also education; trainingquality, definition 1.106–107quality assessment 1.106–108
herbal medicines 1.33–34imported products 1.107legal base 1.108necessity for 1.106pre-marketing 1.112–113
quality assurance/quality control 2.16–17biological preparations 2.111–112definitions 2.15, 2.163excipients 2.82–85GMP 2.52–56, 2.64–65, 2.194, 2.195–
196government laboratories 1.162–174herbal medicines 1.32, 2.129IFPMA training fellowships 1.235–238in vitro dissolution tests 1.83–84investigational products 2.116, 2.123radiopharmaceuticals 2.136–138sampling 1.182–183in site master file 2.157sterile products 2.87tests 2.55, 2.65training programmes 1.15–17
quality audit 2.24–25definition 2.177excipients 2.71–72GMP 2.65, 2.197
quality control areas, GMP 2.33quality control laboratory 1.10–12,
1.154–162, 2.65, 2.111, 2.137official 2.151, 2.173
quality control unit, responsibilities 2.64–65, 2.82
quality defects, WHO CertificationScheme 1.194
quality managementdefinition 2.15ISO 9000-series standards 2.5, 2.67
quality manual 2.184, 2.187–188definition 2.178
quality policydefinition 2.15excipient manufacture 2.70
quality records 2.83quality specifications 1.110–111quality surveillance
during distribution 1.114–115during manufacture 1.113–114
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during marketing 1.113–115, 1.182expertise 1.109imported drugs 1.114national laboratories 1.10–12, 1.154–
162quality system
definition 2.178inspectorates 2.6, 2.176–192ISO 9000-series standards 2.5review 2.148
quantitation, limit of 1.122–123, 1.123quantitative methods, reference
substances 1.125–126quarantine
definition 2.14storage areas 2.31
“r plan”, starting materials sampling1.185–186, 1.186
radiationexposure 2.131safety procedures 2.131–132
radioactive effluents, disposal systems2.132
radioactivity, measuring equipment 2.134radionuclide generators 2.130radiopharmaceuticals 2.130–138
blood or plasma derived 2.133classification 2.130dispensing, packaging and
transportation 2.134GMP 2.4, 2.131labelling 2.134–136personnel 2.131–132premises and equipment 2.132–133production 2.133–134quality assurance/quality control 2.131,
2.136–138records 2.136sampling 2.137–138starting materials 2.134
radiopharmacies 2.130, 2.131random samples, definition 1.178, 1.184–
185randomization systems, investigational
products 2.121range, analytical procedures 1.121–122,
1.123rDNA see recombinant DNAreactions, basic tests 1.151–153reagents 1.118, 1.170–172
GMP 2.38
safety 1.174real-time stability studies 1.48, 1.49–50,
1.54reassessment see inspection, follow-uprecall
definition 2.162records 2.149
recall procedures 2.20–21, 2.117, 2.148,2.171, 2.191
GMP 2.196in site master file 2.157unsatisfactory products 1.109,
1.113recalled products
GMP 2.38storage 2.31
receipt form, example 2.175–176recombinant DNA (rDNA) techniques
2.103, 2.107reconciliation, definition 2.14record keeping
equipment maintenance 2.60–61HACCP 2.210inspection 2.170–171see also documentation
recordsdocumentation 2.46–48GMP inspectorate 2.183–184retention 2.63see also batch records
recovered materialsexcipients 2.74GMP 2.37–38
recovery, definition 2.14re-evaluation dating 2.84reference books, inspection 2.172reference products 1.66
bioequivalence studies 1.74–75choice of 1.85
reference samples, retention 2.63reference sources
for inspector 2.166see also information sources;
International Organization forStandardization (ISO), 9000 seriesstandards
reference standardschemical and biological 2.118GMP 2.39
reference substances 1.8–9, 1.172avoidance of 1.117evaluation 1.127–131
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general guidelines 1.124–136, 1.124–136
handling and distribution 1.131–135ICRS 1.9, 1.135–136, 1.142–148,
1.143–148identity 1.127, 1.128information exchange 1.136information on 1.133–134labelling 1.133–134list of available substances 1.142–148,
1.143–148need establishment criteria 1.125–127purity 1.127, 1.128, 1.129–131WHO Collaborating Centre address
1.143, 1.148see also infrared reference spectra
reflectance techniques 1.141–142registers, reference materials 1.172registration 1.3–6, 1.13, 1.17, 1.217
clinical trials 1.21–22data presentation 1.120definition 1.208licence-holders 1.20multisource products 1.62–104pre-marketing assessment 1.112–113provisional 1.24–25quality specifications 1.110real-time studies 1.54stability testing 1.50test samples 1.52WHO software package 1.3
registration certificate see marketingauthorization; product licence
regulationclinical trials 1.73–74herbal medicines 1.32–33, 1.34multisource products 1.68–69quality assessment 1.108–109
regulatory actions 2.153regulatory authorities 1.2–3, 1.18–30,
1.206, 1.216, 2.141, 2.145, 2.149,2.153, 2.158, 2.159
administrative functions 2.159–160collaboration between 1.19, 1.66, 1.69counterfeit products 1.214, 1.221,
1.223drug control laboratories 1.162–174enforcement arm 2.146generic product licensing 1.30guiding principles 1.2–3, 1.18–30herbal medicines 1.33import legislation 1.211–213
import procedures 1.210–215independence 1.23inspectorate 2.160licensing 1.19–21, 1.25licensing system 2.160powers of enforcement 1.22–23quality assurance 1.106, 1.108,
1.109–110quality surveillance 1.154–155responsibilities 1.19, 1.29, 1.66–67
drug stability 1.41, 1.50multisource products 1.64, 1.66–70
sampling procedures 1.175–186surveillance during marketing
1.113–115, 1.182technical competence 1.23
terms of reference 1.22regulatory testing 2.149re-inspection see inspection, follow-uprejected materials
excipients 2.74GMP 2.37–38, 2.66storage 2.31
repeatability 1.121replication, tests 1.168reports
inspector’s 2.152stability testing 1.55WHO Expert Committee on
Nonproprietary Names forPharmaceutical Substances 1.113
WHO Expert Committee onSpecifications for PharmaceuticalPreparations 1.105–106, 1.110,1.111, 1.163
WHO Expert Group on Requirementsfor Biological Substances:Establishments and ControlLaboratories 1.107–108
WHO Scientific Group on theBioavailability of Drugs: Principlesand Problems 1.107
reprocessed materials, GMP 2.37–38reprocessing, definition 2.14reproducibility, analytical procedures
1.121reserve samples, bioequivalence studies
1.78–79residues
analytical methods/cleaning limits2.73
disposal procedures 2.61
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responsibilitiesdistributors 1.107excipient manufacturer 2.68–70exporting countries 1.66, 1.67importers 1.107individual 2.59manufacturer 2.59personnel 2.25–28pharmacist 1.7, 1.17, 1.42, 1.225procurement agencies 1.42quality control unit 2.64–65regulatory authorities 1.19, 1.29, 1.41,
1.50, 1.64, 1.66–70retention samples 1.169, 2.56
excipients 2.83returned products
GMP 2.38investigational products 2.124procedures 2.171storage 2.31
reworked materials, GMP 2.37–38reworking, definition 2.14rifampicin, bioavailability 1.64risk assessment 1.35robustness, analytical procedures 1.121,
1.123rodent and pest control 2.30rodenticides 2.78
safetyherbal medicines 1.29, 1.34–35laboratories 1.173–174personnel 2.6, 2.10, 2.2111provisionally registered products 1.24–
25quality assessment 1.106–107sampling procedures 1.179–180see also hazard; radiation, safety
proceduressamples/sampling 1.172, 1.175–186
analytical procedures 1.120–121analytical worksheets 1.166–167, 1.168bioequivalence studies 1.77, 1.78–79collection and testing 2.143–144consignment acceptance 1.182–183controls 1.176definitions 1.177–178dosage forms 1.182–183during inspections 1.181, 2.151general precautions 1.179–180government laboratories 1.165–167guidance 2.173–274
herbal medicines 2.129independent analysis 1.14methods, definition 1.177packaging and labelling 1.180–181plans 1.177, 1.184–186, 2.73purpose of 1.175quality assessment 1.163radiopharmaceuticals 2.137–138records 1.177–178reserving 2.144retention 1.169stability studies 1.52–53starting materials 1.183–186storage 2.65surveillance during marketing 1.182testing 1.167–169tools 1.180units 1.179, 1.184–186, 1.186
sanitation 2.18, 2.30clean areas 2.87–88GMP 2.61, 2.196in site master file 2.156written programmes 2.61
screening, provisionally registeredproducts 1.24–25
seed lots, storage 2.106selected samples 1.178selectivity, analytical procedures 1.122,
1.123self-contained area, definition 2.14–15self-inspection 2.23–24, 2.145, 2.146
excipients 2.71–72GMP 2.65, 2.197report 2.24in site master file 2.157team 2.24
sensitivity, analytical procedures 1.122separate areas 2.87shelf-life 1.43, 1.48–49, 1.115
drug stability 1.38–40, 1.41, 1.47provisional 1.43, 1.44storage conditions 1.55–56tropical climates 1.4
shipping/dispatchdefinition 2.116investigational products 2.123–124
significant change, reference substances1.133
Single Convention on Narcotic Drugs(1961, 1972) 1.217
sinks and drains 2.100in clean areas 2.106, 2.132
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site master file 2.155–157small countries, drug regulation 1.18–30software, drug registration package 1.3solvents
infrared spectrophotometry 1.138recovered 2.74residual 2.76
SOPs see standard operating proceduresSPC see Summary of Product
Characteristicsspecifications 1.110–111
definition 2.15documentation 2.41–42essential drugs 1.116finished products 2.43intermediate and bulk products 2.41investigational products 2.119–120repertory 1.170shelf-life 1.49starting and packaging materials 2.41WHO Certification Scheme 1.204
spectrophotometers, calibration 1.173spectrophotometry
reference substances 1.130–131training 1.231see also infrared; ultraviolet
spectrophotometryspillage 2.211sponsor, definition 2.116spore-forming organisms, handling 2.107stability 1.4–6, 1.37–46, 1.49
definition 1.42less stable substances 1.44–45overage 1.40reference substances 1.132–133supporting data 1.49
stability studiesdesign 1.52–54real-time 1.48, 1.49–50, 1.54training 1.232see also accelerated stability studies;
stability testingstability testing 1.46–61, 2.56, 2.65,
2.142accelerated 1.43–44, 1.48, 1.49–50,
1.53, 1.53–54analytical methods 1.54–55climatic zones 1.51, 1.51, 1.52excipients 2.83–84GMP 2.65guidelines 1.4–5, 1.57herbal medicines 1.34, 2.129
inspection 2.150–151intended market 1.51–52objectives 1.49, 1.49–50real-time studies 1.49, 1.54registration/post-registration 1.50reports 1.55sample summary sheets 1.61shelf-life 1.41summary sheet 1.61survey checklist 1.58–60see also accelerated stability studies;
stability studiesstaff/staffing see personnelstandard operating procedures (SOPs)
definitions 2.15, 2.178documentation 2.46–48GMP inspectorate 2.182inspections 2.167, 2.174–175manufacturing operations 2.108radiopharmaceutical production 2.133
standardizationanalytical procedures 1.127drug nomenclature 1.113
standardsGMP 1.188The international pharmacopoeia 1.2see also International Organization for
Standardization (ISO), 9000 seriesstandards
starting materials 1.217definition 2.15excipients 2.74GMP 2.35–36, 2.58–85, 2.63herbal medicines 2.126–127importation 1.214investigational products 2.118quality control 2.54, 2.82radiopharmaceuticals 2.134sampling 1.183–186specifications 2.41, 2.108test requirements 2.55
Statement of Licensing Status 1.190,1.192, 1.200–201
statistical analysis, bioequivalence studies1.79–80, 1.104
sterile products 2.86–102active pharmaceutical ingredients 2.64enclosed areas 2.60excipients 2.80finishing 2.102manufacture 2.88–93processing 2.91–93
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sterility testing 2.87sterilization 2.93–94
by dry heat 2.95by filtration 2.97–98by gases and fumigants 2.96–97by heat 2.94–95by moist heat 2.95by radiation 2.95–96records 2.94SOPs 2.100validation of methods 2.109
sterilizing equipment, validation 2.117stocks, time-expired 1.5, 1.40, 2.171storage
defined instructions 1.43degradation dangers 1.4drug stability 1.38–39, 1.41, 1.47, 1.53facilities 2.31–32, 2.167, 2.170GMP 2.65herbal medicines 2.126imported products 1.211, 1.215normal conditions 1.43outdoor 2.74quality assurance 1.107, 1.108–109,
1.115reagents 1.171–172reference substances 1.131–132shelf-life 1.55–56
subjects, bioequivalence studies 1.75,1.77
Summary Basis of Approval 1.209Summary of Product Characteristics
(SPC) 1.209supplementary guidelines see guidelinessuppliers
audits and approval 2.25identification 2.143new 2.143
supply systemsdrug stability 1.42quality assurance 1.105–115
supporting stability data 1.49surveillance
national laboratories 1.154–162, 1.156,1.159
sampling 1.182testing 2.149see also quality surveillance
surveys, WHO Model List of EssentialDrugs 1.55, 1.58–60
syllabuses, control training programmes1.16–17
teaching, training programmes 1.229–230technical aspects, drug regulation 2.160technical competence, licensing
authorities 1.23technical data, multisource products
1.68–69temperature
mean kinetic 1.48, 1.51–52stability testing 1.51, 1.51–54, 1.52,
1.53storage 1.132
temperature recording devices 2.72tenders 1.29–30, 1.193teratogenicity, herbal substances 1.29,
1.33terminal sterilization 2.93, 2.94–97
see also sterilizationterminally sterilized products 2.90–91terms of reference, national regulatory
authorities 1.22test requirements, quality control 2.55test samples, stability studies 1.52–53tests
documentation of procedures 2.41–42
dosage forms 1.117–119errors 1.168evaluation 1.169samples 1.167–168therapeutic equivalence 1.72–83see also analytical procedures; basic
tests; stability testingtherapeutic equivalence 1.65, 1.67
generic products 1.30in vivo studies 1.67–68marketing authorization 1.69–70see also interchangeability
therapeutically active substances 1.29thin-layer chromatography (TLC)
1.117–119, 1.126, 1.130, 1.157see also chromatography; gas-liquid
chromatography (GLC)time-expired stock 1.5, 1.40, 2.171titrimetric methods
reference substances 1.131training 1.231
TLC see thin-layer chromatographytoilet facilities 2.60tools, sampling 1.180toxicity, herbal products 1.29, 1.32–35toxins 2.207traditional medicine see herbal medicines
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trainees, drug analysis trainingprogramme 1.229, 1.230
training 1.227–238drug analysis programme 1.227–235,
1.231–232IFPMA fellowships 1.235–238import procedures 1.215laboratory services staff 1.156, 1.162personnel 2.28–29, 2.204–205quality control programmes 1.15–17see also education; qualifications
transitimported drugs 1.211quality assurance 1.107
treaties, international drug control 1.217tropical climates
product stability 1.4–6, 1.38, 1.40volatile solvents 1.119
tropical parasitic diseases 1.28tuberculosis, testing for 2.105
ultraviolet irradiation 2.95ultraviolet spectrophotometry 1.125,
1.126, 1.127, 1.130unauthorized markets 2.165
definition 2.163inspection 2.173
UNDCP see United Nations InternationalDrug Control Programme
unhygienic practices 2.60, 2.61uniformity, sampling materials 1.176United Nations International Drug
Control Programme (UNDCP)1.211, 1.222
United States of America (USA)in vivo equivalence study requirements
1.89, 1.89–102legal status of investigational
products 2.113unsatisfactory products, recall 1.109,
1.113use, intended 2.206utilization period, definition 1.44,
1.49
vaccines 2.91, 2.103BCG 2.105killed 2.107requirements 2.104
validationanalytical procedures 1.8, 1.78, 1.119–
124
definitions 2.15, 2.203GMP 2.18–19, 2.196and HACCP 2.201see also process validation
vegetable drug, definition 2.125verification
basic tests 1.153definition 2.203HACCP procedures 2.209–210
victims, counterfeit products 1.220visitors 2.25, 2.29, 2.30visual records of inspection 2.151volatile solvents 1.119, 1.131voucher specimens, herbal medicines
1.33
warehouse/store, inspection 2.170washing
facilities 2.60, 2.100SOPs 2.100written procedure 2.99
waste materialsdisposal procedures 2.61GMP 2.39
water and water systemsin clean areas 2.102in excipient manufacture 2.81–82in manufacture of pharmaceutical
products 2.35monitoring/testing 2.87, 2.92quality standard 2.61
weighing areas, GMP 2.32wholesalers 1.225, 2.159withdrawals procedure 2.191
see also recallwithin-laboratory variation 1.121workers see personnelworking conditions
clean areas 2.106hygienic 2.60
workshopscounterfeit drugs 1.15herbal medicines regulation 1.32
World Customs Organization1.211
World Health Assembly (WHA)GMP inception 2.8–9herbal medicines 1.31–32quality assurance concerns 1.1, 1.12,
2.1–2WHO Certification Scheme 1.188,
1.209–210
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World Health Organization (WHO)Certification Scheme see Certification
Schemepharmaceuticals newsletter 1.189
Requirements for Biological Substances2.104
Revised Drug Strategy 2.1wrist-watches 2.99
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