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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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