Quality Assurance of Pharmaceuticals - A Compendium of Guidelines and Related Materials - Volume 1: 2. Product assessment and registration: Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability 1 : Appendix 1. Examples of national requirements for in vivo equivalence studies for drugs included in the WHO Model List of Essential Drugs (Canada, Germany and the USA, December 1994)

Quality Assurance of Pharmaceuticals - A Compendium of Guidelines and Related Materials - Volume 1
(1997; 248 pages) [French]

Table of Contents

Introduction
	National drug regulation
	Product assessment and registration
	Good manufacturing practices and inspection
	Distribution
	The international pharmacopoeia and related activities
	Basic tests
	Laboratory services
	International trade in pharmaceuticals
	Counterfeit products
	Training
	Conclusion
1. National drug regulation
	Guiding principles for small national drug regulatory authorities^1,2
		1. General considerations
			1.1 The scope of drug control
			1.2 Basic responsibilities
			1.3 Licensing functions
			1.4 Product licences
			1.5 Manufacturers’ and distributors’ licences
			1.6 New drug assessments
			1.7 Authorization of clinical trials
			1.8 Terms of reference of the regulatory authority
			1.9 Powers of enforcement
			1.10 Technical competence
			1.11 Advisory bodies
			1.12 Independence of operation
		2. Administrative aspects of the licensing process
			2.1 Provisional registration of existing medicinal products
			2.2 Screening of provisionally registered products
			2.3 New product licences
			2.4 Renewal and variation of licences
		3. Technical aspects of the licensing process
			3.1 General considerations
			3.2 Products containing long-established chemical entities
			3.3 Products containing new chemical entities
			3.4 Herbal products
			3.5 Combinations of potent, therapeutically active substances
			3.6 Generic products
2. Product assessment and registration
	Guidelines for the assessment of herbal medicines^1,2
	Stability of drug dosage forms¹
		1. Introduction
		2. General considerations
		3. Responsibility of parties involved in the assurance of drug stability
			3.1 Manufacturers
			3.2 Drug regulatory authorities
			3.3 Procurement agencies
			3.4 Pharmacists and other workers in the supply system
		4. Use of terms
		5. Less stable drug substances
		References
	Guidelines for stability testing of pharmaceutical products containing well established drug substances in conventional dosage forms¹
		General
		Definitions
		1. Stability testing
		2. Intended market
		3. Design of stability studies
		4. Analytical methods
		5. Stability report
		6. Shelf-life and recommended storage conditions
		References
		Official, international and national guidelines
		Appendix 1. Survey on the stability of pharmaceutical preparations included in the WHO Model List of Essential Drugs: answer sheet
		Appendix 2. Stability testing: summary sheet
	Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability¹
		Introduction
		Glossary
		Part One. Regulatory assessment of interchangeable multisource pharmaceutical products
			1. General considerations
			2. Multisource products and interchangeability
			3. Technical data for regulatory assessment
			4. Product information and promotion
			5. Collaboration between drug regulatory authorities
			6. Exchange of evaluation reports
		Part Two. Equivalence studies needed for marketing authorization
			7. Documentation of equivalence for marketing authorization
			8. When equivalence studies are not necessary
			9. When equivalence studies are necessary and types of studies required
		Part Three. Tests for equivalence
			10. Bioequivalence studies in humans
			11. Pharmacodynamic studies
			12. Clinical trials
			13. In vitro dissolution
		Part Four. In vitro dissolution tests in product development and quality control
		Part Five. Clinically important variations in bioavailability leading to non-approval of the product
		Part Six. Studies needed to support new post-marketing manufacturing conditions
		Part Seven. Choice of reference product
		Authors
		References
		Appendix 1. Examples of national requirements for in vivo equivalence studies for drugs included in the WHO Model List of Essential Drugs (Canada, Germany and the USA, December 1994)
		Appendix 2. Explanation of symbols used in the design of bioequivalence studies in humans, and commonly used pharmacokinetic abbreviations
		Appendix 3. Technical aspects of bioequivalence statistics
3. Distribution
	Quality assurance in pharmaceutical supply systems¹
		1. Introduction and general considerations
		2. Elements of quality assessment and assurance
			2.1 Legal base
			2.2 Regulatory elements
			2.3 Technical elements
		3. Pre-marketing quality assessment
			3.1 Drug notification, authorization and registration
			3.2 Drug nomenclature
		4. Drug quality surveillance during marketing
			4.1 Quality surveillance during manufacture
			4.2 Quality surveillance of imported drugs
			4.3 Quality surveillance during distribution
		References
4. The international pharmacopoeia and related activities
	Guidance for those preparing or commenting on monographs for preparations to be included in The international pharmacopoeia¹
	Validation of analytical procedures used in the examination of pharmaceutical materials¹
	General guidelines for the establishment, maintenance, and distribution of chemical reference substances¹
		1. Criteria for determining the need for the establishment of chemical reference substances
		2. Evaluation of reference substances
		3. Chemical and physical methods used in evaluating reference substances
			3.1 Methods useful for verifying the identity of reference substances
			3.2 Purity requirements for reference substances
			3.3 Methods used in determining the purity of reference substances
		4. Handling and distribution of reference substances
			4.1 Packing and storage
			4.2 Stability and periodic re-evaluation
			4.3 Information to be supplied with reference substances
			4.4 Expiry of reference substances
			4.5 Distribution problems
		5. Reference materials calibrated against International Chemical Reference Substances
		6. Means of promoting effective exchange of information and ensuring cooperation between organizations establishing reference substances
	General recommendations for the preparation and use of infrared spectra in pharmaceutical analysis¹
	List of available International Chemical Reference Substances¹
	List of available International Infrared Reference Spectra¹
5. Basic tests
	Collaboration within the basic test programme¹
6. Laboratory services
	National laboratories for drug quality surveillance and control¹
		1. Introduction
		2. First-stage laboratory for drug surveillance
		3. Medium-size drug control laboratory
			3.1 Capability
			3.2 Premises
			3.3 Staff
			3.4 Equipment
		4. Scope of activity
		5. Factors influencing the size and location of a laboratory
		6. Implementation of control laboratory projects
			6.1 Feasibility study
			6.2 Phasing of development
			6.3 Programme support
	Good laboratory practices in governmental drug control laboratories¹
		1. General
		2. Management and operational issues
			2.1 Organizational structure
			2.2 Staffing
			2.3 Incoming samples
			2.4 Analytical worksheet
			2.5 Testing
			2.6 Evaluation of test results
			2.7 Retention samples
			2.8 Specifications repertory
			2.9 Reagents
			2.10 Reference materials
			2.11 Instruments and their calibration
			2.12 Safety in drug control laboratories
		References
	Sampling procedure for industrially manufactured pharmaceuticals¹
		1. General considerations
			1.1 Purpose of sampling
			1.2 Types of controls
			1.3 Classes and types of materials
			1.4 Parties concerned with sampling procedures
		2. Use of terms
			2.1 Sampling operations
			2.2 Samples
			2.3 Quantities of material
			2.4 Personnel
		3. General precautions to be taken during sampling operations
		4. Packaging and labelling of samples
		5. Sampling during pharmaceutical inspections
		6. Sampling of pharmaceutical dosage forms in regular surveillance programmes on drug quality during marketing
		7. Sampling of pharmaceutical dosage forms for acceptance of consignments
		8. Sampling of starting materials
			8.1 General considerations
			8.2 Sampling plans for consignments of starting materials supplied in several sampling units
7. International trade in pharmaceuticals
	Guidelines for implementation of the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce¹
		1. Provisions and objectives
		2. Eligibility for participation
		3. Requesting a certificate
		4. Issuing a certificate
		5. Notifying and investigating a quality defect
		References
		Appendix 1. Model Certificate of a Pharmaceutical Product
		Appendix 2. Model Statement of Licensing Status of Pharmaceutical Product(s)
		Appendix 3. Model Batch Certificate of a Pharmaceutical Product
		Appendix 4. Glossary and index
	World Health Assembly resolution WHA50.3: Guidelines on the WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce
	Guidelines on import procedures for pharmaceutical products¹
8. Counterfeit products
	Observations and recommendations on counterfeit drugs^1,2
9. Training
	Training programme in drug analysis^1,2
	Places of training in drug quality control offered by the International Federation of Pharmaceutical Manufacturers Associations¹
Selected WHO publications of related interest
Back cover

Appendix 1. Examples of national requirements for in vivo equivalence studies for drugs included in the WHO Model List of Essential Drugs (Canada, Germany and the USA, December 1994)

General

National requirements for equivalence studies for specific drug products differ from country to country. National requirements for equivalence studies of a specific drug product can be based on any of the following:

- case-by-case study;
- criteria established by a national advisory committee; or
- application of the national regulatory guidelines.

A list of examples is presented in Table 1. It is intended to be illustrative only, in accordance with the guidelines, and does not represent a formal recommendation.

The list is based on substances and products included in the WHO Model List of Essential Drugs (1), but only includes essential drugs for which in vivo studies are required because of the nature of the dosage form. Some dosage forms, e.g. solutions and injections, have therefore been omitted from the list as they have not been identified as requiring studies in one of the three countries covered.

Examples of decisions on criteria taken by national authorities

Canada

At present, demonstration of bioequivalence is required for those drugs which are not considered to have been marketed in Canada for their intended purpose(s) for sufficient time and in sufficient quantity to establish safety and efficacy (new drugs). Bioequivalence may be demonstrated by comparative bioequivalence studies or by clinical studies including, where applicable, acceptable surrogate models. Scientific criteria, similar to those of the European Community and Australia, are being developed for deciding in which situations in vivo demonstration of bioequivalence is required for drugs that are not new.

Germany

Over the past years, the National Advisory Committee has taken the decision on the need for a comparative bioavailability/bioequivalence study as a requirement for marketing authorization. These decisions have been based on published data for the drug substance and its dosage form, and on the use of an algorithm. Details of the algorithm, the criteria and the resulting decisions have been published in the German Federal Register. In certain circumstances, the regulatory authority takes decisions on a case-by-case basis.

USA

Drug products introduced before 1938 in the USA do not require approval for marketing and therefore no in vivo equivalence study is needed. The majority of drug products, other than solution dosage forms, approved between 1938 and 1962, and known to have potential bioavailability problems, require in vivo equivalence studies. Generally, drug products approved after 1962, with the exception of solution dosage forms, also require in vivo equivalence studies.

Table 1. Examples of national requirements for equivalence studies¹

¹ +: in vivo studies required; +b: bioequivalence studies; +p: pharmacodynamic studies: +c: clinical trials; -: no in vivo studies required; ?: decision on the type of in vivo studies pending; O: no information available, no final decision taken, or not available on national market.

Drug substance	Dosage form	Canada	Germany	USA
acetazolamide	tablet, 250 mg	+b	+b	+b
acetylsalicylic acid	suppository, 50-150 mg	?	+b	-
	tablet, 100-500 mg	-	+b	-
albendazole	tablet, 200 mg	o	+b	o
allopurinol	tablet, 100 mg	+b	+b	+b
aluminium hydroxide	oral suspension, 320 mg/5 ml	-	+p	-
	tablet, 500 mg	-	+p	-
amiloride hydrochloride	tablet, 5 mg	+b	-	+b
aminobenzoic acid	cream	?	+p+c	-
	gel	?	+p+c	-
	lotion	?	+p+c	-
aminophylline	tablet, 100 mg, 200 mg	?	o	+b
amitriptyline hydrochloride	tablet, 25 mg	?	+b	+b
amoxicillin	capsule, 250 mg, 500 mg	+b	+b	+b
	powder for oral suspension, 125 mg/5 ml	+b	+b	+b
	tablet, 250 mg, 500 mg	+b	+b	+b
ascorbic acid	tablet, 50 mg	-	?	-
atenolol	tablet, 50 mg, 100 mg	+b	-	+b
atropine sulfate	solution (eye drops), 0.1%, 0.5%, 1%	o	+c	-
	tablet, 1 mg	o	?	o
azathioprine	tablet, 50 mg	+b	+b	+b
bacitracin zinc	ointment, 500 IU + neomycin sulfate, 5 mg/g	o	+c	-
beclometasone dipropionate	inhalation, 50 µg/dose	?	+p+c	+p
benzathine benzylpenicillin	powder for injection, 1.44 g of benzylpenicillin (= 2.4 million ID) in 5-ml vials	o	-	+b
benznidazole	tablet, 100 mg	o	+b	o
benzoic acid	cream, 6% + salicylic acid, 3%	-	+p+c	o
	ointment, 6% + salicylic acid, 3%	-	+p+c	-
benzoyl peroxide	cream, 5%	-	+p+c	-
	lotion, 5%	-	+p+c	-
benzyl benzoate	lotion, 25%	-	+p+c	o
betamethasone valerate	cream, 0.1% of betamethasone	+p	+p+c	+p
	ointment, 0.1% of betamethasone	+p	+p+c	+p
biperiden hydrochloride	tablet, 2 mg	+b	+b	+b
calamine	lotion	-	+p+c	-
calcium folinate	tablet, 15 mg	+b	o	+b
captopril	tablet, 25 mg	+b	-	+b
carbamazepine	tablet, 100 mg, 200 mg	+b	+b	+b
carbidopa	tablet, 10 mg + levodopa, 100 mg	+b	+b	+b
	25 mg + levodopa, 250 mg	+b	+b	+b
chloramphenicol	capsule, 250 mg	?	+b	+b
chloramphenicol palmitate	oral suspension, 150 mg of chloramphenicol/5 ml	?	+b	+b
chloramphenicol sodium succinate	oily suspension, injection, 0.5 g of chloramphenicol/ml in 2-ml ampoule	o	+b	o
chloroquine hydrochloride	injection, 40 mg of chloroquine/ml in 5-ml ampoule	o	-	-
chloroquine phosphate	tablet, 150 mg of chloroquine	o	+b	-
chloroquine sulfate	tablet, 150 mg of chloroquine	o	+b	o
chlorphenamine hydrogen maleate	tablet, 4 mg	-	?	-
chlorpromazine hydrochloride	tablet, 100 mg	?	+b	+b
ciclosporin	capsule, 25 mg	+b	+b	+b
cimetidine	tablet, 200 mg	+b	-	+b
ciprofloxacin hydrochloride	tablet, 250 mg of ciprofloxacin	+b	+b	+b
clofazimine	capsule, 50 mg, 100 mg	o	+b	+b
clomifene citrate	tablet, 50 mg	+b	+b	+b
clomipramine hydrochloride	capsule, 10 mg, 25 mg	+b	o	+b
cloxacillin sodium	capsule, 500 mg of cloxacillin	?	+b	+b
codeine phosphate	tablet, 10 mg, 30 mg	o	-	-
colchicine	tablet, 500 µg	?	+b	-
cyclophosphamide	tablet, 25 mg	+b	+b	+b
dapsone	tablet, 50 mg, 100 mg	?	+b	+b
desmopressin acetate	nasal spray, 10 µg/metered dose	+b+p	+p+c	?
dexamethasone	tablet, 500 µg, 4 mg	?	?	+b
diazepam	scored tablet, 2 mg, 5 mg	+b	-	+b
diethylcarbamazine dihydrogen citrate	tablet, 50 mg	o	+b	+b
digitoxin	tablet, 50 µg, 100 µg	?	+b	-
digoxin	tablet, 62.5 µg, 250 µg	?	+b	-
diloxanide furoate	tablet, 500 µg	o	+b	o
dimercaprol	injection, in oil, 50 mg/ml in 2-ml ampoule	+b+c	+b¹	-
dioxybenzone	cream	?	+p+c	o
	lotion	?	+p+c	o
	gel	?	+p+c	o
dithranol	ointment, 0.1-2%	-	+p+c	-
doxycycline hyclate	capsule, 100 mg of doxycycline	+b	+b	+b
	tablet, 100 mg of doxycycline	+b	+b	+b
ergocalciferol	capsule, 1.25 mg (50 000 IU)	o	+b	-
	tablet, 1.25 mg (50 000 IU)	o	+b	-
ergometrine hydrogen maleate	tablet, 200 µg	?	+b	-
ergotamine tartrate	tablet, 2 mg	o	+b	-
erythromycin ethylsuccinate	capsule, 250 mg of erythromycin	?	+b	+b
	powder for oral suspension, 125 mg of	?	+b	+b
	erythromycin tablet, 250 mg of erythromycin	?	+b	+b
erythromycin stearate	capsule, 250 mg of erythromycin	?	+b	+b
	powder for oral suspension, 125 mg of	?	+b	+b
	erythromycin tablet, 250 mg of erythromycin	?	+b	+b
ethambutol hydrochloride	tablet, 100-400 mg	+b	+b	+b
ethinylestradiol	tablet, 50 µg	+b	+b	+b
	tablet, 30 µg + levonorgestrel, 150 µg	+b	+b	+b
	tablet, 50 µg + levonorgestrel, 250 µg	+b	+b	+b
	tablet, 35 µg + norethisterone, 1.0 mg	+b	+b	+b
ethosuximide	capsule, 250 mg	?	+b	+b
etoposide	capsule, 100 mg	+b	+b	+b
ferrous sulfate	tablet, 60 mg of Fe	-	o	-
	tablet, 60 mg of Fe + folic acid, 250 µg	-	o	-
flucytosine	capsule, 250 mg	+b	+b	+b
fludrocortisone acetate	tablet, 100 µg	+b	+b	+b
fluorouracil	ointment, 5%	+c	+p+c	?
fluphenazine decanoate	injection, 25 mg in 1-ml ampoule	?	+b¹	-
fluphenazine enantate	injection, 25 mg in 1-ml ampoule	?	+b¹	-
folic acid	tablet, 5 mg, 1 mg	+b	+b	-
	tablet, 250 µg + ferrous sulfate, 60 mg of Fe	-	+b	-
furosemide	tablet, 40 mg	+b	+b	+b
gentamicin sulfate	solution (eye drops), 0.3%	+c	+p+c	-
glyceryl trinitrate	tablet (sublingual), 500 µg	?	+b	-
griseofulvin	capsule, 125 mg, 250 mg	?	+b	+b
	tablet, 125 mg, 250 mg	?	+b	+b
haloperidol	tablet, 2 mg, 5 mg	+b	-	+b
hydralazine hydrochloride	tablet, 25 mg, 50 mg	o	+b	-
hydrochlorothiazide	tablet, 25 mg, 50 mg	?	-	+b
hydrocortisone acetate	cream, 1%	o	+p+c	-
	ointment, 1%	o	+p+c	-
	suppository, 25 mg	o	+p+c	?
ibuprofen	tablet, 200 mg	+b	-	+b
idoxuridine	eye ointment, 0.2%	o	+p+c	+c
	solution (eye drops) 0.1%	o	-	-
indometacin	capsule, 25 mg	+b	-	+b
	tablet, 25 mg	+b	-	o
insulin: insulin (soluble)	injection, 40 IU/ml in 10-ml vial,	+b	-	+b+p
	80 IU/ml in 10-ml vial,	+b	-	+b+p
	100 IU/ml in 10-ml vial	+b	-	+b+p
insulin zinc suspension	injection, 40 IU of insulin/ml in 10-ml vial	+b	o	+b+p
	80 IU of insulin/ml in 10-ml vial	+b	o	+b+p
insulin (intermediate- acting)	100 IU of insulin/ml in 10-ml vial	+b	-	+b+p
isophane insulin	injection, 40 IU of insulin/ml in 10-ml vial	+b	+b	+b+p
	80 IU of insulin/ml in 10-ml vial	+b	+b	+b+p
	100 IU of insulin/ml in 10-ml vial	+b	+b	+b+p
iodized oil	capsule, 200 mg	?	o	o
iopanoic acid	tablet, 500 mg	o	o	-
iron dextran	injection, 50 mg of Fe/ml in 2-ml ampoule	+c	-	+b+p
isoniazid	tablet, 100-300 mg	+b	+b	-
	tablet, 100 mg + rifampicin, 150 mg	o	+b	+b
	tablet, 150 mg + rifampicin, 300 mg	o	+b	+b
	tablet, 100 mg + thioacetazone, 50 mg	o	+b	o
	tablet, 300 mg + thioacetazone, 150 mg		+b	o
isosorbide dinitrate	tablet (sublingual), 5 mg	+b	+b	+b
ivermectin	scored tablet, 6 mg	o	+b	o
ketoconazole	oral suspension, 100 mg/5 ml	+b	+b	+b
	tablet, 200 mg	+b	+b	+b
levamisole hydrochloride	tablet, 50 mg, 150 mg	+b	+b	+b
levodopa	tablet, 100 mg + carbidopa, 10 mg	+b	+b	+b
	250 mg + carbidopa, 25 mg	+b	+b	+b
levonorgestrel	tablet, 150 µg + ethinylestradiol, 30 µg	+b	+b	+b
	tablet, 250 µg + ethinylestradiol, 50 µg	+b	+b	+b
levothyroxine sodium	tablet, 50 µg, 100 µg	?	+b	-
lithium carbonate	capsule, 300 mg	+b	+b	+b
	tablet, 300 mg	+b	+b	+b
mebendazole	chewable tablet, 100 mg	+b	+b	+b+c
medroxyprogesterone acetate (depot)	injection, 150 mg/ml in 1-ml vial,	?	+b	+b
	injection, 50 mg/ml in 3-ml vial	?	+b	+b
mefloquine hydrochloride	tablet, 250 mg	+b	+b	+b
mercaptopurine	tablet, 50 mg	+c+b	+b	+b
methionine (DL-)	tablet, 250 mg	?	?	-
methotrexate sodium	tablet, 2.5 mg of methotrexate	+b+c	+b	+b
methyldopa	tablet, 250 mg	?	+b	+b
metoclopramide hydrochloride	tablet, 10 mg of metoclopramide	+b	-	+b
metrifonate	tablet, 100 mg	o	+b	o
metronidazole	suppository, 500 mg, 1 g	o	+b	o
	tablet, 200-500 mg	+b	+b	+b
metronidazole benzoate	oral suspension, 200 mg of metronidazole/5 ml	o	+b	o
mexenone	cream	o	+p+c	o
	lotion	o	+p+c	o
	gel	o	+p+c	o
miconazole nitrate	cream, 2%	+c	+p+c	+c
	ointment, 2%	+c	+p+c	+c
morphine sulfate	tablet, 10 mg	o	+b	-
nalidixic acid	tablet, 500 mg	+b	+b	+b
neomycin sulfate	ointment, 5 mg + bacitracin zinc, 500 IU/g	o	+p+c	-
neostigmine bromide	tablet, 15 mg	?	?	-
niclosamide	chewable tablet, 500 mg	o	+b	+b
nicotinamide	tablet, 50 mg	-	?	-
nifedipine	capsule, 10 mg	+b	+b	+b
	tablet, 10 mg	+b	+b	o
nifurtimox	tablet, 30 mg, 120 mg, 250 mg	o	+b	o
nitrofurantoin	tablet, 100 mg	?	+b	+b
norethisterone	tablet, 350 µg, 5 mg	+b	+b	o
	tablet, 1.0 mg + ethinylestradiol, 35 µg	+b	+b	o
norethisterone enantate	oily solution, 200 mg/ml in 1-ml ampoule	?	+b	o
nystatin	lozenge, 100000 IU	+	?	+b
	tablet, 100 000 IU, 500 000 IU	o	-	-
oxamniquine	capsule, 250 mg	o	+b	+b
oxybenzone	cream	-	+p+c	+c
	gel	-	+p+c	+c
	lotion	-	+p+c	+c
paracetamol	suppository, 100 mg	+b	-	o
	tablet, 100-500 mg	-	-	o
penicillamine	capsule, 250 mg	+b	-	+b
	tablet, 250 mg	+b	-	+b
permethrin	lotion, 1%	-	+p+c	+c
pethidine hydrochloride	tablet, 50 mg, 100 mg	o	+b	-
phenobarbital	tablet, 15-100 mg	-	o	-
phenoxymethylpenicillin potassium	powder for oral suspension, 250 mg of phenoxymethylpenicillin/5 ml	o	+b	+b
	tablet, 250 mg of phenoxymethylpenicillin	?	+b	+b
phenytoin sodium	capsule, 25 mg, 100 mg	+b	+b	+b
	tablet, 25 mg, 100 mg	+b	+b	o
phytomenadione	tablet, 10 mg	+b	o	+b
pilocarpine hydrochloride	solution (eye drops), 2%, 4%	o	+p+c	-
pilocarpine nitrate	solution (eye drops), 2%, 4%	o	+p+c	o
piperazine adipate	tablet, 500 mg of piperazine hydrate	-	o	o
piperazine citrate	tablet, 500 mg of piperazine hydrate	-	o	+b
podophyllum resin	solution, topical, 10-25%	o	+p+c	-
potassium iodide	tablet, 60 mg	-	-	-
praziquantel	tablet, 150 mg, 600 mg	o	+b	+b
prednisolone	solution (eye drops), 0.5%	o	+p+c	o
	tablet, 1 mg, 5 mg	?	+b	+b
primaquine diphosphate	tablet, 7.5 mg of primaquine, 15 mg of primaquine	?	+b	-
procainamide hydrochloride	tablet, 250 mg, 500 mg	+b	+b	+b
procaine benzylpenicillin	powder for injection, 1 g (= 1 million IU),	?	-	+b
	3 g (= 3 million IU)	o		+b
procarbazine hydrochloride	capsule, 50 mg	+c+b	+b	+b
proguanil hydrochloride	tablet, 100 mg	o	+b	o
promethazine hydrochloride	tablet, 10 mg, 25 mg	?	+b	+b
propranolol hydrochloride	tablet, 10 mg, 20 mg, 40 mg, 80 mg	+b	+b	+b
propyliodone	oily suspension, 500-600 mg/ml in 20-ml ampoule	o	o	-
propylthiouracil	tablet, 50 mg	?	-	+b
pyrantel embonate	oral suspension, 50 mg of pyrantel/ml	o	+b	+b
	chewable tablet, 250 mg of pyrantel	o	+b	o
pyrazinamide	tablet, 500 mg	+b	+b	+b
pyridostigmine bromide	tablet, 60 mg	+b	?	+b
pyridoxine hydrochloride	tablet, 25 mg	-	?	-
pyrimethamine	tablet, 25 mg + sulfadoxine, 500 mg	+b	+b	+b
quinidine sulfate	tablet, 200 mg	?	+b	+b
quinine bisulfate	tablet, 300 mg of quinine	+b	+b	-
quinine sulfate	tablet, 300 mg of quinine	?	+b	-
reserpine	tablet, 100 µg, 250 µg	?	+b	+b
retinol palmitate	capsule, 200 000 IU (110 mg) of retinol	-	?	o
	sugar-coated tablet, 10 000 IU of retinol	-	?	o
riboflavin	tablet, 5 mg	-	?	-
rifampicin	capsule, 150 mg, 300 mg	+b	+b	+b
	tablet, 150 mg, 300 mg	+b	+b	+b
	tablet, 150 mg + isoniazid, 100 mg	o	+b	+b
	300 mg + isoniazid, 150 mg	o	+b	+b
salbutamol sulfate	inhalation (aerosol), 100 µg of salbutamol per dose	?,+p	+p+c	+p
	respirator solution for use in nebulizers, 5 mg/ml	?,+p	+p+c	-
	tablet, 2 mg, 4 mg of salbutamol	+b	+b	+b
salicylic acid	cream, 3% + benzoic acid, 6%	-	+p+c	o
	ointment, 3% + benzoic acid, 6%	-	+p+c	-
	solution, topical, 5%	-	+p+c	o
silver nitrate	solution (eye drops), 1%	o	+p+c	-
silver sulfadiazine	cream, 1% in 500-g container	+c	+p+c	+c
sodium cromoglicate	inhalation, 20 mg/dose	? or +c	+p+c	+p+c
sodium fluoride	tablet, 500 µg	-	-	-
sodium valproate	enteric coated tablet, 200 mg, 500 mg	+b	+b	+b
spironolactone	tablet, 25 mg	+b	+b	+b
sulfadimidine	tablet, 500 mg	o	+b	o
sulfadoxine	tablet, 500 mg + pyrimethamine, 25 mg	+b	+b	+b
sulfamethoxazole	oral suspension 200 mg + trimethoprim, 40 mg/5 ml	+b	+b	+b
	tablet, 100 mg + trimethoprim, 20 mg	+b	+b	+b
	400 mg + trimethoprim, 80 mg	+b	+b	+b
sulfasalazine	tablet, 500 mg	+b	+b	+b
tamoxifen citrate	tablet, 10 mg of tamoxifen, 20 mg of tamoxifen	+b	+b	+b
testosterone enantate	injection, 200 mg in 1 ml ampoule	?	+b	-
tetracaine hydrochloride	solution (eye drops), 0.5%	o	+p+c	-
tetracycline hydrochloride	capsule, 250 mg	?	+b	+b
	tablet, 250 mg	?	+b	+b
	eye ointment, 1%	?	+p+c	-
thiamine hydrochloride	tablet, 50 mg	-	?	-
thioacetazone	tablet, 50 mg + isoniazid, 100 mg	o	+b	o
	150 mg + isoniazid, 300 mg	o	+b	o
tolbutamide	tablet, 500 mg	+b	+b	+b
trimethoprim	oral suspension, 40 mg + sulfamethoxazole, 200 mg/5 ml	+b	+b	+b
	tablet, 100 mg, 200 mg	+b	+b	+b
	tablet, 20 mg + sulfamethoxazole, 100 mg	+b	+b	+b
	80 mg + sulfamethoxazole, 400 mg	+b	+b	+b
tropicamide	solution (eye drops), 0.5%	o	+p+c	-
verapamil hydrochloride	tablet, 40 mg, 80 mg	+b	+b	+b
warfarin sodium	tablet, 1 mg, 2 mg, 5 mg	?	+b	+b
zinc oxide	cream	-	+p+c	-
	ointment	-	+p+c	-

¹ “Depot” preparation for injection.

Reference

1. The use of essential drugs. Sixth report of the WHO Expert Committee. Geneva, World Health Organization, 1995 (WHO Technical Report Series, No. 850).