WHO TECHNICAL REPORT SERIES
VOL. 1999, NO. 885, 1999
Contents
1. Introduction 1
2. The international pharmacopoeia and related issues 2
2.1 Quality specifications for drug substances and dosage forms 2
2.2 Simple test methodology 3
3. International Chemical Reference Substances and Infrared Reference
Spectra 4
3.1 Establishment of International Chemical Reference Substances 4
3.2 International Infrared Reference Spectra 5
3.3 Use of International Chemical Reference Substances and Infrared
Reference Spectra 5
3.4 Guidelines for the establishment, maintenance and distribution of
chemical reference substances 5
4. Quality control — national laboratories 6
4.1 Good laboratory practices in government drug equality control
laboratories 6
4.2 Information on external quality assessment 6
4. Good manufacturing practices 6
5.1 Adoption of additional guidelines 6
5.2 Good manufacturing practices for sterile products 7
5.3 Relationship between pharmacopoeia) requirements and
manufacturers' internal specifications 7
6. Quality systems and inspection 7
6.1 Quality systems for GMP inspectorates 7
6.2 Pre-approval inspection 7
6.3 Guidelines for inspection of drug distribution channels 8
6.4 Use of simple test methods by inspectors 8
7. Other quality assurance topics 8
7.1 Compendia 8
7.2 Packaging for pharmaceutical products 8
7.3 Multisource pharmaceutical products 8
7.4 Guidelines for good pharmacy practice 9
8. Nomenclature and terminology 9
8.1 International Nonproprietary Names for pharmaceutical
substances 9
8.2 Terminology 9
9. Legal aspects of pharmaceuticals 10
9.1 Drug regulatory legislation 10
9.2 National implementation guidelines for combating counterfeit
pharmaceuticals 10
10. Regulatory issues 11
10.1 WHO Certification Scheme on the Quality of Pharmaceutical
Products Moving in International Commerce 11
10.1.1 Finished pharmaceutical products 11
10.1.2 Active pharmaceutical ingredients 11
10.2 WHO model system for computer-assisted drug registration 11
10.3 Model guidelines for the international provision of controlled
medicines for emergency medical care 12
11. Training activities 12
11.1 Training programmes for drug regulators and related activities 12
1 1.2 Training programmes for the detection of counterfeit
pharmaceutical products 13
12. Pharmaceuticals contaminated with diethyleneglycol 13
Acknowledgements 13
References 17
Annex 1
List of available International Chemical Reference Substances 20
Annex 2
List of available International Infrared Reference Spectra 27
Annex 3
General guidelines for the establishment, maintenance and distribution of
chemical reference substances 29
Annex 4
Good manufacturing practices: authorized person — role, functions
and training 45
Annex 5
Good manufacturing practices: supplementary guidelines for the
manufacture of pharmaceutical excipients 50
Annex 6
Guidelines for inspection of drug distribution channels 72
Annex 7
Good pharmacy practice in community and hospital pharmacy settings 93
Annex 8
National drug regulatory legislation: guiding principles for small drug
regulatory authorities 102
Annex 9
Provisional guidelines for developing training programmes: inspection and
examination of counterfeit pharmaceuticals 143
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NO.886 , 1999
Introduction 1
The goals and guiding concepts Programming for adolescent health
2. Goals of programming 2
2.1 Background 2
2.2 Promoting healthy development 5
2.3 Preventing and responding to health problems 9
3. Guiding concepts
3.1 Background 15
3.2 Adolescent development underlies prevention of health problems 17
3.3 problems have common roots and are interrelated 19
3.4 adolescence is a time of opportunity and risk 20
3.5 Social environment influences adolescent health 22
3.6 Not all young people are equally vulnerable 23
3.7 Gender considerations are fundamental 25
Making a difference — interventions that work
4.1 Major interventions 28
4.1 Background 28
4.2 promoting a safe and supportive environment 39
4.3 Providing information 55
4.4 Building skills 72
4.5 Counselling 80
4.6 Health services 90
5. Intervention settings
5.1 Background 98
5.2 Home 98
5,3 School 99
5.4 Health centres 101
5.5 Workplace 111
5.6 Street 113
5.7 Community organization 115
5.8 Residential centre 118
5.9 Media/entertainment 121
5.10 Political/legislative systems 122
6. Keys to success
6.1 Background 122
6.2 putting young people at the centre of programming 124
addressing multiple health problems simultaneously 125
6.4 combining interventions 127
6.5 building on and linking existing intervention in various settings 129
6.6 respecting cultural diversity 131
6.7 strengthening programme management 137
6.8 Encouraging positive adult attitudes and behaviour 141
The challenges of programming for adolescent health
7. Building political commitment 144
7.1 Background 144
7.2 Adolescents are regarded as healthy 150
7.3 Reluctance to confront sensitive issues 151
7.4 Investing in young people is seen as a drain on social and
economic resources 153
8. Assessing priorities for action 156
8.1 Background 156
8.2 Data collection and analysis by age and sex 161
8.3 Compiling data from different sectors 162
8.4 Systematically involving young people in assessing priorities 164
8.5 Determining the target groups 168
9. Maintaining implementation 169
9.1 Background 169
9.2 Fostering adult-youth partnerships 170
9.3 Reorienting and sustaining existing interventions through training 175
9.4 Coordinating activities in multiple settings 176
9.5 Continual recruitment of young people as human resources 180
9.6 Achieving large-scale programming 181
10. Monitoring and evaluation 187
10.1 Background 187
10.2 Establishing and using indicators 196
10.3 Tracking quality and coverage in different settings 205
10.4 Understanding the impact of young people's participation
throughout programming 209
11. Conclusions 212
12. 1 Recommendations 215
12.1 Recommendations to WHO, UNFPA and UNICEF 215
12.2 Recommendations to countries • 217
Acknowledgements 218
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WHO TECHNICAL REPORT SERIES
VOL. 1999, NO.887, 1999
Contents
1. Introduction 1
2. Critical review of psychoactive substances 1
2.1 Scheduling criteria 1
2.1.1 Narcotic drugs 2
2.1.2 Psychotropic substances 3
2.2 Dihydroetorphine 4
2.3 Ephedrine 6
2.4 Remifentanil (INN) 8
2.5 Proposal of the Government of Spain 10
2.5.1 Outline of the proposal 10
2.5.2 Conclusions and recommendations 10
3. Pre-review of psychoactive substances 11
3.1 Benzodiazepines 12
3.2 Tobacco 13
3.2.1 Previous review 13
3.2.2 International framework convention for tobacco control 13
3.2.3 Summary and recommendation 13
3.3 Gamma-hydroxybutyric acid (GHB) 14
3.4 4- Bromo-2,5-dimethoxyphenethylamine (2C-B) 15
3.5 N/-Methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB) 16
3.6 Zolpidem (INN) 17
3.7 Substances for future review 18
4. Other issues 18
4.1 Guideline revision 18
4.2 Substance nomenclature 19
Acknowledgements 19
References 19
Annex
Letter addressed to the United Nations Secretary-General communicating
the proposal of the Government of Spain 21
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WHO TECHNICAL REPORT SERIES
VOL. 1999, NO. 888, 1999
Contents
1. Introduction 1
2. General considerations 2
2.1 Modification of the agenda 2
2.2 Neurotoxicity of avermectins and milbemycins 2
2.3 Evaluation policy of the Committee in the establishment of MRLs
for veterinary drugs in food 3
3. Comments on residues of specific veterinary drugs 4
3.1 Anthelminthic agents 4
3.1.1 Eprinomectin 4
3.1.2 Febantel, fenbendazole and oxfendazole 13
3.1.3 Moxidectin 19
3.2 Antimicrobial agents 21
3.2.1 Gentamicin 22
3.2.2 Procaine benzylpenicillin 25
3.2.3 Sarafloxacin 33
3.2.4 Spectinomycin 43
3.2.5 Tetracyclines: chlortetracycline, oxytetracycline and
tetracycline 50
3.3 Antiprotozoal agents 54
3.3.1 Diclazuril 54
3.3.2 Imidocarb 56
3.3.3 Nicarbazin 66
3.4 Glucocorticosteroid 72
3.4.1 Dexamethasone 72
3.5 Production aid 74
3.5.1 Recombinant bovine somatotropins (rbSTs) 74
3.6 Tranquillizing agent 79
3.6.1 Azaperone 79
4. Recommendations 81
Acknowledgement 81
References 82
Annex1
Reports and other documents resulting from previous meetings of the
Joint FAO/WHO Expert Committee on Food Additives 83
Annex 2
Recommendations on compounds on the agenda and further toxicological
studies and other information required 90
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WHO TECHNICAL REPORT SERIES
NO:884, 1999
1 . Introduction 1
2. General considerations 1
2.1 Modification of the agenda 2
2.2 Principles goveming the toxicological evaluation of
compounds on the agenda 2
2.2. l Procedure for the Safety Evaluation of Flavouring
Agents 3
2.2.2 Role of the Committee in the risk analysis process of
the Codex Alimentarius Commission 6
2.3 Principles goveming the establishment and revision of
specifications 6
2.3.1 Significance of identity and purity requirements 6
2.3.2 Limits for arsenic, lead and other heavy metals 7
2.3.3 Analytical methods 7
2.3.4 Enzymes derived from genetically modified organisrns 8
2.3.5 Flavouring agents 8
2.4 Principles governng intake assessments of food additives
and contaminants 9
2.4.1 Methods for assessing dietary intake 9
2.4.2 Assessment of dietary intake of specific additives 10
3. Specific food additives and food ingredients 11
3.1 Antioxidant: tert-butylhydroquinone(TBHQ) 11
3.2 Emulsifiers 14
3.2.1 Microcrystalline cellulose 14
3.2.2 Sucrose esters of fatty acids and sucroglycerides 16
3.3 Enzyme preparations 17
3.3.1 alpha-Acetolactate decarboxylase 17
3.3.2 Maltogenic amylase 18
3.4 Flavouring agent: trans-anethole 20
3.5 Glazing agent: hydrogenated poly-1-decene 21
3.6 Sweetening agent: maltitol syrup 21 .
3.7 Miscellaneous substance: salatrim (short- and long-chain
acyltriglyceride molecules) 23
4. Substances evaluated using the Procedure for the Safety
Evaluation of Flavouring Agents 25
4.1 Allyl-2-furoate 28
4.2 Saturated aliphatic acyclic linear primary alcohols,
aldehydes and acids 29
4.3 Saturated aliphatic acyclic branched-chain primary alcohols,
aldehydes and acids 37
4.4 Aliphatic lactones 42
4.5 Esters of aliphatic acyclic primary alcohols with branched-chain
aliphatic acyclic acids 52
4.6 Esters of aliphatic acyclic primary alcohols with aliphatic linear
saturated carboxylic acids 56
4,7 Esters derived from branched-chain terpenoid alcohols and
aliphatic acyclic carboxylic acids
4.8 Specifications for flavouring agents 6
5. Contaminants: aflatoxins 6
6. Revision of certain specifications 7
7. Recommendations 8
Acknowledgement 8
References 8
Annex 1
Reports and other documents resulting from previous meetings of the
Joint FAO/WHO Export Committee on Food Additives 8
Annex 2
Acceptable Daily Intakes, other toxicological information, and information
on specifications 8
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