WHO Expert Committee on Specifications for Pharmaceutical Preparations - WHO Technical Report Series, No. 902 - Thirty-sixth Report (2002; 219 pages)  Table des matières
Annex 11 - Guidance on the selection of comparator pharmaceutical products for equivalence assessment of interchangeable multisource (generic) products
Introduction
This annex provides a list of comparator products for equivalence assessment of interchangeable multisource (generic) products. The information on comparator pharmaceutical products was collected by the Secretariat from drug regulatory authorities and pharmaceutical companies. The list has been drawn up to assist regulatory authorities and pharmaceutical companies in deciding on appropriate comparator products in the context of multisource (generic) marketing authorization. The information could also be used for drug procurement purposes. Where the comparator pharmaceutical product is not clearly defined, criteria are suggested that are provided in a decision-tree format (see Figure 1). This permits the selection of a comparator pharmaceutical product.
The guidelines on registration requirements to establish interchange-ability of multisource (generic) pharmaceutical products published by WHO (1) state that multisource products must satisfy the same standards of quality, safety and efficacy as those applicable to the corresponding innovator product. They recommend that quality attributes of a multisource product should be tested against the innovator product for which interchange is intended.
The innovator product is usually the most logical comparator product because its quality, safety and efficacy should have been well assessed in pre- and post-marketing studies and in addition, the data on its safety and efficacy are usually linked to a pharmaceutical product with defined specifications for quality and performance. Despite acceptance of the general objective, there is no agreement on the criteria for selecting a list of international comparator products, nor does a list of such products exist. The comparator product chosen is either the most widely used “leading’” product on the market or the product that was first introduced in that market. For this reason, among others, significant differences may exist between the comparator products used in different countries.
Figure 1 Decision-tree for use in identifying a comparator pharmaceutical product
In the light of the various approaches currently under scientific and regulatory discussion, the feasibility of developing a system of international comparator products was considered. This initiative led to the recommendations given here, which replace those of Part Seven of the previously published WHO guidelines on multisource pharmaceutical products (1).
A list of international comparator pharmaceutical products for equivalence assessment of interchangeable multisource (generic) products1 is given in Table 1.
1 The list is based on information collected by WHO from drug regulatory authorities and supplemented with that from pharmaceutical companies. It will be periodically updated.
Instructions on the use of the list
1. National regulatory authorities may issue this guidance together with Lists A and B, which should be available to applicants/pharmaceutical companies that plan to develop multisource pharmaceutical products intended to be interchangeable with innovator or other pharmaceutical products of established quality, safety and efficacy.
2. List A provides information about pharmaceutical products from the WHO Model List of Essential Drugs (2) and includes the innovator products (column headed “Trademark”) and the national markets where the manufacturers in question consider that their products’ quality, safety and efficacy are best documented (column headed “Primary market”).
3. Pharmaceutical companies planning to develop an interchangeable multisource pharmaceutical product should determine whether the innovator pharmaceutical product appearing in List A is available on the local market.
4. If the innovator pharmaceutical product is available on the local market, pharmaceutical companies should use this product in equivalence assessment with their multisource product.
5. If the innovator product is not available on the local market, pharmaceutical companies should obtain from the market a product that is the best representative innovator product from the point of view of its quality, safety and efficacy (see column headed “Primary market” of List A).
6. The type of equivalence assessment of the comparator pharmaceutical product and the multisource product under investigation may vary, depending on local requirements and the availability of resources. Recommendations on the type of equivalence studies to be carried out when such studies are necessary are given in the WHO guidelines on multisource pharmaceutical products (1).
7. For some pharmaceutical products, an innovator product cannot be identified. Examples of these products from the WHO Model List of Essential Drugs (2) appear in List B. For these products, a local, national or regional pharmacopoeia or The international pharmacopoeia (3) for both the drug substance and, when available, the product, supplemented by official reference texts, may provide sufficient information and requirements to allow a pharmaceutical company to develop a product of the requisite quality, safety and efficacy. No international comparator product for these pharmaceutical products will be available, and no equivalence assessment can be performed.
Also included in List B are pharmaceutical products for which an innovator product can be identified or a marker leader product may be available, but for which there is insufficient information available for them to appear in List A, e.g. products for which the originator no larger exists or which cannot be traced. The List A approach can also be applied to these products.
8. When a market leader product is available on the local market but no innovator product can be identified or obtained from the primary market, the market leader product may be used as a comparator product if its quality, safety and efficacy have been established. If this is not the case, the second market leader or compendial standards approach (List B) can be followed.
Most of the pharmaceuticals listed are included in the WHO Model List of Essential Drugs (2). In the case of products for which equivalence testing is required, it should be performed in accordance with the WHO guidelines on registration requirements to establish inter-changeability of multisource (generic) products (1).
Layout of the list
Pharmaceutical name (1) |
Section no. (2) |
Dosage forms and strengths (3) |
Comparator pharmaceutical products (4) |
| |
|
|
Trademark |
Primary market |
Manufacturer |
albendazole |
6.1.1 |
chtab, 200 mg |
Zentel |
France |
SmithKline Beecham |
The list is divided into two parts, as follows:
• List A provides information on comparator pharmaceutical products - trademark and primary market - as given by manufacturers of innovator products.
• List B contains products for which information has not been given by manufacturers of innovator or market leader products or difficulties in providing the information were encountered because the pharmaceutical products have been marketed for a long time.
(1) Pharmaceutical name: International Nonproprietary Names (INNs) are used to identify the active drug substance as in the WHO Model List of Essential Drugs.
(2) Section no.: this corresponds to the WHO Model List of Essential Drugs, and indicates the therapeutic uses/pharmacological effects of the pharmaceutical.
(3) Dosage forms and strengths: these correspond to the WHO Model List of Essential Drugs. A strike-through means that no products of the dosage form or strength are available on the market. An entry in bold signifies that a product of the dosage form or strength is available on the market instead of, or in addition to, those in the WHO Model List of Essential Drugs.
The following abbreviations are used:
cap |
capsule |
cheap |
chewable capsule |
chtab |
chewable tablet |
cre |
cream |
elix |
elixir |
encotab |
enteric-coated tablet |
eyd |
eye drop |
eyo |
eye ointment |
inh |
inhalation |
inj |
injection/injectable solution |
lot |
lotion |
loz |
lozenge |
multi |
multiple |
nsp |
nasal spray |
oilinj |
injection in oil |
oilsl |
oily solution |
oilsp |
oil suspension |
oilspinj |
oil suspension injection |
oin |
ointment |
oosl |
oral oily solution |
osl |
oral solution |
osp |
oral suspension |
pes |
pessary |
pwinj |
powder for injection |
pwosp |
powder for oral suspension |
pwsl |
powder for solution |
respsl |
respirator solution |
sbltab |
tablet, sublingual |
sctab |
scored tablet |
sgtab |
sugar-coated tablet |
sl |
solution |
sr |
sustained-release preparation |
sup |
suppository |
syr |
syrup |
tab |
tablet |
topsl |
solution, topical |
vagtab |
vaginal tablet |
wminj |
water-miscible injection |
(4) Comparator pharmaceutical products: “Trademark” and “Primary market” for List A indicate the innovator products and the national markets where the manufacturers in question consider that their products’ quality, safety and efficacy are best documented.
List B, which does not give this information, follows the pharmacopoeial standards approach.
The entry ***** means that additional information on the product must be provided before it can be included in List A.
Table 1
International comparator products for equivalence assessment of interchangeable multisource (generic) productsa
Pharmaceutical name |
Section no. |
Dosage forms and strengths |
Comparator pharmaceutical products |
| |
|
|
Trademark |
Primary market |
Manufacturer |
List A |
albendazole |
6.1.1 |
chtab, 200 mg |
Zentel |
France |
SmithKline Beecham |
amiloride, hydrochloride |
16 |
tab, 5 mg |
Midamor |
United Kingdom |
Merck, Sharp & Dohme |
aminophylline |
25.1 |
tab, 100 mg, 200 mg (sr), 125 mg |
Aminophylin |
Germany |
BYK Gulden Lomberg |
amitriptyline, hydrochloride |
24.2.1 |
tab, 25 mg |
Elavil |
USA |
Zeneca |
amoxicillin |
6.2.1 |
cap, 250 mg, 500 mg pwosp, 125 mg/5 ml tab, 250 mg, 500 mg |
Amoxil |
United Kingdom |
SmithKline Beecham |
atenolol |
12.1 |
tab, 50 mg, 100 mg |
Tenormin |
United Kingdom |
Zeneca |
| |
12.2 |
tab, 50 mg, 100 mg |
|
|
|
| |
12.3 |
tab, 50 mg, 100 mg |
|
|
|
atropine, sulfate |
21.5 |
eyd, 0.1%, 0.5%, 1% |
Atropin Dispersa |
Switzerland |
Ciba Vision (Novartis) |
benznidazole |
6.5.5 |
tab, 100 mg |
Radanil |
Argentina, Brazil, Switzerland |
Roche |
biperiden, hydrochloride |
9 |
tab, 2 mg |
Akineton |
Germany |
Knoll |
captopril |
12.3 |
sctab, 25 mg |
Capoten |
USA |
Bristol-Myers Squibb |
carbamazepine |
5 |
sctab, 100 mg, 200 mg (sr) |
Tegretol |
Switzerland |
Novartis |
chloramphenicol |
6.2.2 |
cap, 250 mg |
Chloromycetin |
USA |
Parke-Davis |
chloramphenicol, sodium succinate |
6.2.2 |
oilspinj, 0.5g/2 ml |
Chloromycetin sodium succinate |
USA |
Parke-Davis/Parkedale |
chloroquine, phosphate |
6.5.3 |
tab, 25 mg, 100 mg,b 150 mg,b,c 500 mg |
Alaren phosphate |
USA |
Sanofi Winthrop |
chlorphenamine, hydrogen maleate |
3 |
tab, 4 mg |
Chlortrimeton |
USA |
Schering-Plough |
ciclosporin |
8.1 |
cap, 25 mg |
Sandimmun |
Switzerland |
Novartis |
cimetidine |
17.1 |
tab, 200 mg |
Tagamet |
France |
SmithKline Beecham |
ciprofloxacin, hydrochloride |
6.2.2 |
tab, 250 mg |
Ciprobay |
Germany |
Bayer |
clofazimine |
6.2.3 |
cap, 50 mg, 100 mg |
Lamprene |
Switzerland |
Novartis |
clomifene, citrate |
18.6 |
tab, 50 mg |
Clomid |
USA |
Hoechst Marion Roussel |
clomipramine, hydrochloride |
24.4 |
cap, 10 mg, 25 mg |
Anafranil |
Switzerland |
Novartis |
clonazepam |
5 |
sctab, 500 µg |
Rivotril |
Switzerland |
Roche |
cloxacillin, sodium |
6.2.1 |
cap, 500 mg |
Penstaphon |
Belgium |
Bristol-Myers Squibb |
| |
|
pwsl, 125 mg/5 ml |
Tegopen |
USA |
|
cyclophosphamide |
8.2 |
tab, 25 mg, 50 mg |
Endoxana |
United Kingdom |
ASTA Medica |
dapsone |
6.2.3 |
tab, 25 mg, 50 mg, 100 mg |
Dapsone |
USA |
Jacobus |
desmopressin, acetate |
10.2 |
nsp, 10 µg/metered dose |
DDAVP |
USA |
Ferring |
dexamethasone |
3 |
tab, 500 µg, 4 mg |
Decadron |
USA |
Merck, Sharp & Dohme |
| |
18.1 |
tab, 500 µg, 4 mg |
|
|
|
diazepam |
24.3 |
sctab, 2 mg, 5 mg |
Valium |
USA |
Roche |
doxazosin mesilate |
12.3 |
tab, 1 mg, 2 mg, 4 mg |
Caldura |
Germany |
Pfizer |
doxycycline, hyclate |
6.2.2 |
cap, 100 mg |
Vibramycin |
Germany |
Pfizer |
| |
|
tab, 100 mg |
|
|
|
epinephrine, hydrochloride |
21.5 |
eyd, 2% |
Suprarenin |
Germany |
Hoechst Marion Roussel |
ergocalciferol |
27 |
cap, 1.25 mg (50 000 IU) osl, 250 µg/ml (10 000 IU/ml) tab, 1.25 mg (50 000 IU) |
Drisdol |
USA |
Sanofi |
ethinylestradiol |
18.4 |
tab, 10 µg, 20 µg, 50 µg |
Pregynon C |
Germany |
Schering |
ethinylestradiol + levonorgestrel |
18.3.1 |
tab, 30 µg + 150 µg, 50 µg+ 250 µg |
Nordette-21 |
USA |
Wyeth-Ayerst |
ethosuximide |
5 |
cap, 250 mg syr, 250 mg/5 ml |
Zarontin |
USA |
Parke-Davis |
etoposide |
8.2 |
cap, 100 mg |
Vepesid |
Netherlands |
Bristol-Myers Squibb |
| |
|
inj, 20 mg/ml, 50 mg/ml |
|
USA |
|
flucytosine |
6.3 |
cap, 250 mg |
Ancobon |
USA |
ICN Pharmaceuticals |
fludrocortisone, acetate |
18.1 |
tab, 100 µg |
Florinef |
USA |
Bristol-Myers Squibb |
fluorouracil |
13.5 |
oin, 5% |
Efudix |
USA |
Roche |
fluphenazine, decanoate |
24.1 |
depot inj, 25 mg/ml |
Prolixin decanoate |
USA |
Bristol-Myers Squibb |
fluphenazine, enantate |
24.1 |
depot inj, 25 mg/ml |
Prolixin enanthate |
USA |
Bristol-Myers Squibb |
furosemide |
16 |
tab, 40 mg |
Lasix |
Germany |
Hoechst Marion Roussel |
glyceryl trinitrate |
12.1 |
sbltab, 500 µg
|
Nitroglycerin Wander |
Switzerland |
Novartis |
| |
|
chcap, 800 µg |
|
|
|
griseofulvin |
6.3 |
cap, 125 mg, 250 mg |
Grisactin |
USA |
Zeneca |
| |
|
tab, 125 mg, 250 mg |
Fulcin |
USA |
|
haloperidol |
24.1 |
tab, 2 mg, 5 mg |
Haldol |
Belgium |
Janssen |
hydralazine, |
12.3 |
tab, 25 mg, 50 mg |
Apresoline |
Netherlands |
Novartis |
| |
hydrochloride |
|
pwinj, 20 mg |
|
United Kingdom |
|
hydrochlorothiazide |
12.3 |
tab, 25 mg |
Hydrosaluric |
United Kingdom |
Merck, Sharp & Dohme |
| |
16 |
tab, 25 mg, 50 mg |
|
|
|
ibuprofen |
2.1 |
tab, 200 mg |
Nurofen |
UK |
Boots |
idoxuridine |
21.1 |
eyd, 0.1% |
Herplex |
USA |
Allergan |
| |
|
eyo, 0.2% |
|
|
|
imipenem (monohydrate) + cilastin (sodium) |
6.2.1 |
pwinj, 250 mg + 250 mg, 500 mg + 500 mg |
Tienam |
Italy |
Merck, Sharp & Dohme |
| |
|
pwinj, 500 mg + 500 mg |
|
|
|
insulin injection (soluble) |
18.5 |
inj, 40 IU/ml, 80 IU/ml, |
Actrapid |
Germany |
Novo Nordisk |
| |
|
100 IU/ml
|
|
|
|
| |
|
inj, 40 IU/ml, 80 IU/ml, |
Actrapid |
Zimbabwe |
|
| |
|
100 IU/ml |
|
|
|
| |
|
inj, 40 IU/ml, 80 IU/ml, |
Novolin R |
Japan, USA |
|
| |
|
100 IU/ml |
|
|
|
intermediate-acting insulin (as compound insulin zinc suspension) |
18.5 |
inj, 40 IU/ml, 80 IU/ml, 100 IU/ml |
Humulin L |
USA |
Eli Lilly |
intermediate-acting insulin (as isophane insulin) |
18.5 |
inj, 40 IU/ml, 80 IU/ml, 100 IU/ml |
Humulin N |
USA |
Eli Lilly |
ipratropium bromide |
25.1 |
inh, 20 µg/metered dose |
Atrovent |
USA |
Boehringer Ingelheim |
iron dextran |
10.1 |
inj, equiv. to 50 mg iron/ml |
Infed |
USA |
Shein Pharmaceuticals |
isosorbide dinitrate |
12.1 |
sbltab, 5 mg |
Isordil |
USA |
Wyeth-Ayerst |
ivermectin |
6.1.2 |
sctab, 6 mg |
Mectizan/Stromectol |
Netherlands |
Merck, Sharp & Dohme |
ketoconazole |
6.3 |
osp, 100 mg/5 ml tab, 200 mg |
Nizoral |
Belgium |
Janssen |
levamisole, hydrochloride |
6.1.1 |
tab, 50 mg, 150 mg |
Ergamisol |
Belgium |
Janssen |
| |
8.2 |
tab, 50 mg |
|
|
|
levodopa + carbidopa |
9 |
tab, 100 mg + 10 mg, 250 mg + 50 mg |
Sinemet |
Italy |
Merck, Sharp & Dohme |
levonorgestrel |
18.3.1 |
tab, 30 µg |
Microval |
Germany |
Wyeth-Ayerst |
lithium carbonate |
24.2.2 |
cap, 300 mg tab, 300 mg |
Quilonum |
Germany |
SmithKline Beecham |
mebendazole |
6.1.1 |
chtab, 100 mg, 500 mg |
Vermox |
Belgium |
Janssen |
medroxyprogesterone |
18.3.1 |
depot inj, 150 mg/ml |
Depo-Provera |
USA |
Pharmacia-Upjohn |
acetate |
18.7 |
tab, 5 mg |
Provera |
|
|
mefloquine, hydrochloride |
6.5.3 |
tab, 250 mg |
Lariam |
Switzerland |
Roche |
methyldopa |
12.3 |
tab, 250 mg |
Aldomet |
Spain |
Merck, Sharp & Dohme |
metoclopramide, hydrochloride |
17.2 |
tab, 10 mg |
Primperan |
France |
Synthlabo |
miconazole, nitrate |
13.1 |
cre, 2% |
Daktarin |
Belgium |
Janssen |
| |
|
oin, 2% |
|
|
|
nalidixic acid |
6.2.2 |
tab, 500 mg
|
Neggran |
USA |
Sanofi Winthrop |
| |
|
cap, 500 mg |
|
|
|
neostigmine, bromide |
20 |
tab, 15 mg |
Prostigmin |
Germany |
Roche |
niclosamide |
6.1.1 |
chtab, 500 mg |
Yomesan |
Germany |
Bayer |
nifedipine |
12.3 |
cap, 10 mg (sr) |
Adalat 10 |
Germany |
Bayer |
| |
|
tab, 10 mg (sr) |
Adalat T 10 |
|
|
nifurtimox |
6.5.5 |
tab, 30 mg, 120 mg, 250 mg |
Lampit |
Argentina |
Bayer |
nitrofurantoin |
6.2.2 |
tab, 100 mg |
Furadantin |
Ireland, United Kingdom |
Proctor & Gamble |
norethisterone enantate |
18.3.1 |
oilsl, 200 mg/ml |
Noristerat |
Mexico, South Africa |
Schering |
nystatin |
6.3 |
loz, 100 000 IU |
Nystan |
United Kingdom |
Bristol-Myers Squibb |
| |
|
pes, 100 000 IU
|
Mycostatine |
France |
|
| |
|
tab, 100 000 IU |
|
France |
|
| |
|
tab, 500 000 IU |
|
USA |
|
| |
|
vagtab, 100 000 IU |
|
France |
|
oxamniquine |
6.1.3 |
cap, 250 mg |
Mansil/Vansil |
Brazil |
Pfizer |
| |
|
syr, 250 mg/5 ml |
|
|
|
paracetamol |
2.1 |
sup, 100 mg, 125 mg, 250 mg, |
Ben-U-Ron |
Germany |
Bene |
| |
|
500 mg, 1000 mg |
|
|
|
penicillamine |
4.2 |
cap, 250 mg |
Cuprimine |
USA |
Merck, Sharp & Dohme |
| |
|
tab, 250 mg |
Depen |
|
Cater-Wallace |
phenobarbital |
5 |
tab, 15-100 mg |
Luminal (100 mg) |
Germany |
Desitin |
| |
|
|
Luminaletten (15 mg) |
|
|
phenoxymethylpenicillin, |
6.2.1 |
pwosp, 250 mg/5 ml |
V-Cillin K |
USA |
Eli Lilly |
potassium |
|
tab, 250 mg |
|
|
|
phenytoin, sodium |
5 |
cap, 25 mg, 30 mg, 50 mg |
Dilantin Kapseals |
USA |
Parke-Davis |
| |
|
100 mg |
|
|
|
| |
|
tab, 25 mg, 50 mg, 100 mg |
Dilantin Infatabs |
|
|
phytomenadione |
10.2 |
tab, 10 mg |
Konakion |
Switzerland |
Roche |
praziquantel |
6.1.1 |
tab, 150 mg, 600 mg |
Biltricide |
Germany |
Bayer |
| |
6.1.3 |
tab, 600 mg |
|
|
|
prednisolone |
3 |
tab, 5 mg |
Scherisolon |
Colombia, Uruguay |
Schering |
| |
8.3 |
tab, 5 mg |
|
|
|
| |
18.1 |
tab, 1 mg, 5 mg |
|
|
|
| |
21.2 |
eyd, 0.5% |
Ultracortenol |
Germany |
Ciba Vision (Novartis) |
procainamide, hydrochloride |
12.2 |
tab, 250 mg, 500 mg |
Pronestyl |
USA |
Bristol-Myers Squibb |
procarbazine, hydrochloride |
8.2 |
cap, 50 mg |
Natulan |
Switzerland |
Roche |
proguanil, hydrochloride |
6.5.3 |
tab, 100 mg |
Paludrine |
United Kingdom |
Zeneca |
propranolol, |
7.2 |
tab, 20 mg, 40 mg |
Inderal |
Japan |
Zeneca |
hydrochloride |
- |
tab, 10 mg, 40 mg |
|
United Kingdom |
|
pyrantel, embonate |
6.1.1 |
chtab, 250 mg |
Combantrin |
Germany |
Pfizer |
| |
|
osp, 50 mg/ml |
|
|
|
pyrazinamide |
6.2.4 |
tab, 400 mg, 500 mg |
Zinamide |
United Kingdom |
Merck, Sharp & Dohme |
pyridostigmine, bromide |
20 |
tab, 60 mg |
Mestinon |
Switzerland |
Roche |
rifampicin |
6.2.3 |
cap, 150 mg, 300 mg |
Rifadin |
Italy |
Gruppo Lepetit |
| |
|
tab, 150 mg, 300 mg |
|
|
|
| |
6.2.4 |
cap, 150 mg, 300 mg |
|
|
|
| |
|
tab, 150 mg, 300 mg |
|
|
|
rifampicin + isoniazid |
6.2.4 |
tab, 150 mg + 100 mg, 300 mg + 150 mg |
Rifinah |
Italy |
Gruppo Lepetit |
rifampicin + isoniazid |
6.2.4 |
tab, 150 mg + 75 mg |
Rifater |
Italy |
Hoechst Marion Roussel |
+ pyrazinamide |
|
+ 400 mg, 150 mg |
|
|
|
| |
|
+ 150 mg + 500 mg |
|
|
|
silver sulfadiazine |
13.2 |
cre, 1%/500 g |
Silvadene |
USA |
Hoechst Marion Roussel |
sulfadoxine + pyrimethamine |
6.5.3 |
tab, 500 mg + 25 mg |
Fansidar |
Switzerland |
Roche |
sulfamethoxazole + trimethoprim |
6.2.2 |
osp, 200 mg + 40 mg/5 ml |
Bactrim |
Switzerland |
Roche |
| |
|
tab, 100 mg + 20 mg, 400 mg+ 80 mg |
|
|
|
sulfasalazine |
17.4 |
tab, 500 mg |
Azulfidine |
USA |
Pharmacia-Upjohn |
tamoxifen, citrate |
8.3 |
tab, 10 mg, 20 mg |
Nolvadex |
United Kingdom |
Zeneca |
testosterone, enantate |
18.2 |
inj, 200 mg/ml, 250 mg/ml |
Testorion depot |
Argentina, Germany, Mexico |
Schering |
theophylline |
25.1 |
tab, 100 mg, 125 mg,
200 mg , |
Euphylong |
Germany |
BYK-Gulden |
| |
|
250 mg, 375 mg, 500 mg |
|
|
|
timolol, maleate |
21.4 |
sl (eyd), 0.25%, 0.5% |
Timoptol ophthalmic solution |
France |
Merck, Sharp &Dohme |
| |
|
eyd, 0.25%, 0.5% (unit dose) |
Timoptol Ocudose |
|
|
| |
|
gel (eyd), 0.25%, 0.5% |
Timoptol LP |
|
|
tolbutamide |
- |
tab, 500 mg |
Rastinon |
Germany |
Hoechst Marion Roussel |
triclabendazole |
6.1.3 |
tab, 250 mg |
Egaten |
Egypt |
Novartis |
tropicamide |
14.1 |
eyd, 0.5% |
Mydriacyl |
United Kingdom |
Alcon |
verapamil, hydrochloride |
12.1 |
tab, 40 mg, 80 mg (sr) |
Isoptin |
Germany |
Knoll |
| |
12.2 |
tab, 40 mg, 80 mg (sr) |
|
|
|
List B |
acetazolamide |
21.4 |
tab, 250 mg |
***** |
|
|
acetylsalicylic acid |
2.1 |
sup, 50-150 mg |
***** |
|
|
| |
|
tab, 100-500 mg |
***** |
|
|
| |
7.1 |
tab, 300-500 mg |
***** |
|
|
| |
12.5 |
tab, 100 mg |
***** |
|
|
aciclovir |
6.4.1 |
tab, 200 mg |
***** |
|
|
aciclovir (sodium) |
6.4.1 |
pwinj, 250 mg |
***** |
|
|
allopurinol |
2.3 |
tab, 100 mg |
***** |
|
|
aluminium hydroxide |
17.1 |
osp, 320 mg/5 ml |
|
|
|
| |
|
tab, 500 mg |
|
|
|
amoxicillin + clavulanic acid |
6.2.1 |
tab, 500 mg + 125 mg |
***** |
|
|
ascorbic acid |
27 |
tab, 50 mg |
|
|
|
atropine, sulfate |
17.5 |
tab, 1 mg |
***** |
|
|
azathioprine |
8.1 |
tab, 50 mg |
***** |
|
|
beclometasone, dipropionate |
25.1 |
inh, 50 µg/dose |
***** |
|
|
benzoic acid + salicylic acid |
13.1 |
cre, 6% + 3% |
|
|
|
| |
|
oin, 6% + 3% |
|
|
|
benzoyl peroxide |
13.5 |
cre, 5% |
|
|
|
| |
|
lot, 5% |
|
|
|
benzoyl benzoate |
13.6 |
lot, 25% |
|
|
|
betamethasone, valerate |
13.3 |
cre, 0.1% |
***** |
|
|
| |
|
oin, 0.1% |
***** |
|
|
calamine lotion |
13.3 |
lot |
|
|
|
chloral hydrate |
1.3 |
syr, 200 mg/5 ml |
|
|
|
chloramphenicol, |
6.2.2 |
osp, 150 mg/5 ml |
***** |
|
|
palmitate |
|
|
|
|
|
chloroquine, phosphate |
6.5.3 |
syr, 50 mg/5 mlb,c |
***** |
|
|
chloroquine, sulfate |
6.5.3 |
syr, 50 mg/5 mlb,c |
|
|
|
| |
|
tab, 100 mg,b 150 mgb,c |
|
|
|
chlorpromazine, |
24.1 |
syr, 25 mg/5 ml |
***** |
|
|
hydrochloride |
|
tab, 100 mg |
***** |
|
|
coal tar |
13.5 |
topsl, 5% |
|
|
|
codeine, phosphate |
2.2 |
tab, 30 mg |
***** |
|
|
| |
17.7.2 |
tab, 30 mg |
***** |
|
|
colchicine |
2.3 |
tab, 500 µg |
***** |
|
|
cromoglicic acid, sodium |
25.1 |
inh, 20 mg/dose |
***** |
|
|
dextromethorphan |
25.2 |
osl, 3.5 mg/5 ml |
***** |
|
|
diethylcarbamazine, dihydrogen citrate |
6.1.2 |
tab, 50 mg |
***** |
|
|
diethyltoluamide |
6.6 |
topsl, 50%, 75% |
|
|
|
digitoxin |
- |
tab, 50 µg, 100 µg |
***** |
|
|
digoxin |
12.4 |
osl, 50 µg/ml |
***** |
|
|
| |
|
tab, 62.5 µg, 250 µg |
***** |
|
|
diloxanide, furoate |
6.5.1 |
tab, 500 mg |
***** |
|
|
dimercaprol |
4.2 |
oilinj, 50 mg/ml |
***** |
|
|
dithranol |
13.5 |
oin, 0.1-2% |
***** |
|
|
ergometrine, hydrogen maleate |
22.1 |
tab, 200 µg |
***** |
|
|
ergotamine, tartrate |
7.1 |
tab, 1 mg |
|
|
|
erythromycin, ethyl succinate |
6.2.2 |
cap, 250 mg |
***** |
|
|
| |
|
pwosp, 125 mg |
***** |
|
|
| |
|
tab, 250 mg |
***** |
|
|
erythromycin, stearate |
6.2.2 |
cap, 250 mg |
***** |
|
|
| |
|
pwosp, 125 mg |
***** |
|
|
| |
|
tab, 250 mg |
***** |
|
|
ethambutol, hydrochloride |
6.2.4 |
tab, 100-400 mg |
***** |
|
|
ethinylestradiol + norethisterone |
18.3.1 |
tab, 35 µg + 1.0 mg |
***** |
|
|
ferrous salt, sulfate |
10.1 |
osl, equiv. to 25 mg iron/ml |
|
|
|
| |
|
tab, equiv. to 60 mg iron |
|
|
|
ferrous salt (sulfate) + folic acid |
10.1 |
tab, equiv. to 60 mg iron + |
|
|
|
| |
|
250 µg folic acid |
|
|
|
folic acid |
10.1 |
tab, 1 mg, 5 mg |
***** |
|
|
gentamicin, sulfate |
21.1 |
eyd, 0.3% |
***** |
|
|
glibenclamide |
18.5 |
tab, 2.5 mg, 5 mg |
***** |
|
|
hydrocortisone, acetate |
13.3 |
cre, 1% |
***** |
|
|
| |
|
oin, 1% |
***** |
|
|
| |
17.4 |
supp, 25 mg |
***** |
|
|
hydrogen peroxide |
- |
sl, 3% |
|
|
|
iopanoic acid |
14.2 |
tab, 500 mg |
***** |
|
|
ipecacuanha |
4.1 |
syr, 0.14%, as emetine |
|
|
|
isoniazid |
6.2.4 |
tab, 100-300 mg |
***** |
|
|
isoniazid + ethambutol |
6.2.4 |
tab, 150 mg + 400 mg |
***** |
|
|
levothyroxine, sodium |
18.8 |
tab, 50 µg, 100 µg |
***** |
|
|
magnesium hydroxide |
17.1 |
osp, equiv. to 550 mg/10 ml |
|
|
|
mercaptopurine |
8.2 |
tab, 50 mg |
***** |
|
|
metformin |
18.5 |
tab, 500 mg |
***** |
|
|
DL-methionine |
4.2 |
tab, 250 mg |
***** |
|
|
methotrexate, sodium |
8.2 |
tab, 2.5 mg |
***** |
|
|
metrifonate |
- |
tab, 100 mg |
***** |
|
|
metronidazole |
6.2.2 |
sup, 500 mg, 1 g |
***** |
|
|
| |
|
tab, 200-500 mg |
***** |
|
|
| |
6.5.1 |
tab, 200-500 mg |
***** |
|
|
metronidazole, benzoate |
6.5.1 |
osp, 200 mg/5 ml |
***** |
|
|
morphine, hydrochloride |
2.2 |
osl, 10 mg/5 ml |
|
|
|
morphine, sulfate |
2.2 |
osl, 10 mg/5 ml |
|
|
|
| |
|
tab, 10 mg |
|
|
|
neomycin, sulfate + bacitracin zinc |
13.2 |
oin, 5 mg + 500 IU |
***** |
|
|
nicotinamide |
27 |
tab, 50 mg |
|
|
|
norethisterone |
18.7 |
tab, 5 mg |
***** |
|
|
paracetamol |
2.1 |
syr, 125 mg/5 ml |
|
|
|
| |
|
tab, 100-500 mg |
|
|
|
| |
7.1 |
tab, 300-500 mg |
|
|
|
permethrin |
13.6 |
lot, 1% |
|
|
|
pethidine, hydrochloride |
2.2 |
tab, 50 mg, 100 mg |
***** |
|
|
phenobarbital |
5 |
elix, 15 mg/5 ml |
***** |
|
|
pilocarpine, hydrochloride or nitrate |
21.4 |
sl (eyd), 2%, 4% |
***** |
|
|
podophyllum resin |
13.5 |
topsl, 10-25% |
|
|
|
potassium iodide |
18.8 |
tab, 60 mg |
|
|
|
primaquine, diphosphate |
6.5.3 |
tab, 7.5 mg, 15 mg |
***** |
|
|
promethazine, hydrochloride |
1.3 |
elix, 5 mg/5 ml |
***** |
|
|
| |
|
syr, 5 mg/5 ml |
***** |
|
|
| |
17.2 |
elix, 5 mg/5 ml |
***** |
|
|
| |
|
syr, 5 mg/5 ml |
***** |
|
|
| |
|
tab, 10 mg, 25 mg |
***** |
|
|
propyliodone |
14.2 |
oilsp, 500-600 mg/ml |
***** |
|
|
propylthiouracil |
18.8 |
tab, 50 mg |
***** |
|
|
pyridoxine, hydrochloride |
27 |
tab, 25 mg |
|
|
|
quinidine, sulfate |
12.2 |
tab, 200 mg |
***** |
|
|
quinine, bisulfate |
6.5.3 |
tab, 300 mg |
|
|
|
quinine, sulfate |
6.5.3 |
tab, 300 mg |
|
|
|
reserpine |
12.3 |
tab, 100 µg, 250 µg |
***** |
|
|
retinol, palmitate |
27 |
cap, 200 000 IU (110 mg) |
|
|
|
| |
|
oosl, 100 000 IU/ml |
|
|
|
| |
|
sgtab, 10 000 IU (5.5 mg) |
|
|
|
| |
|
wminj, 100 000 IU/2 ml (55 mg) |
|
|
|
riboflavin |
27 |
tab, 5 mg |
|
|
|
salbutamol, sulfate |
22.2 |
tab, 4 mg |
***** |
|
|
| |
25.1 |
inh, 100 µg/dose |
***** |
|
|
| |
|
respsl, 5 mg/ml |
***** |
|
|
| |
|
syr, 2 mg/5 ml |
***** |
|
|
| |
|
tab, 2 mg, 4 mg |
***** |
|
|
salicylic acid |
13.5 |
topsl, 5% |
|
|
|
senna (sennoside) |
17.6 |
tab, 7.5 mg |
|
|
|
silver nitrate |
21.1 |
sl (eyd), 1% |
|
|
|
sodium fluoride |
27 |
any |
|
|
|
spironolactone |
16 |
tab, 25 mg |
***** |
|
|
sulfadiazine |
6.2.2 |
tab, 500 mg |
***** |
|
|
sulfadimidine |
- |
osp, 500 mg/5 ml |
***** |
|
|
| |
|
tab, 500 mg |
***** |
|
|
tetracaine, hydrochloride |
21.3 |
sl (eyd), 0.5% |
***** |
|
|
tetracycline, hydrochloride |
21.1 |
eyo, 1% |
***** |
|
|
thiamine, hydrochloride |
27 |
tab, 50 mg |
|
|
|
thioacetazone + isoniazid |
6.2.4 |
tab, 50 mg + 100 mg, 150 mg |
***** |
|
|
| |
|
+ 300 mg |
|
|
|
trimethoprim |
6.2.2 |
tab, 100 mg, 200 mg |
***** |
|
|
urea |
13.5 |
cre, 10% |
|
|
|
| |
|
oin, 10% |
|
|
|
valproic acid, sodium |
5 |
encotab, 200 mg, 500 mg |
***** |
|
|
warfarin, sodium |
10.2 |
tab, 1 mg, 2 mg, 5 mg |
***** |
|
|
zidovudine |
6.4.2 |
cap, 100 mg, 250 mg |
***** |
|
|
| |
|
osl, 50 mg/5 ml |
***** |
|
|
zinc oxide |
- |
cre |
|
|
|
| |
|
oin |
|
|
|
a For instructions on the use of the list, see pages 164-167.
b For curative treatment.
c For prophylaxis.
Authors
This guidance was discussed during two meetings convened by the Division of Drug Management and Policies and the Department of Essential Drugs and other Medicines, World Health Organization, Geneva, Switzerland, from 12 to 13 February 1996 and from 8 to 9 February 1999. The meetings were attended by the following people:
Mr M.N. Dauramanzi, Drugs Control Council. Harare, Zimbabwe
Professor U. Gundert-Remy, University of Göttingen, Göttingen, Germany
Dr M. Holz-Slomczyk, Federal Institute for Drugs and Medical Devices, Berlin, Germany
Mrs M. Ikeda, Ministry of Health and Welfare. Tokyo, Japan
Dr K. Morimoto, Pharmaceuticals and Medical Devices Evaluation Centre, National Institute of Health Sciences, Tokyo, Japan
Ms A. Poompanich, Division of Drug Analysis, Ministry of Public Health, Nonthaburi, Thailand
Dr R. Williams, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, MD, USA
Secretariat
Mrs K. Bremer, Quality Assurance and Safety: Medicines, Essential Drugs and other Medicines, WHO, Geneva, Switzerland
Dr M. Demesmaeker, Quality Assurance and Safety: Medicines, Essential Drugs and other Medicines, WHO, Geneva, Switzerland
Dr J. Idänpään-Heikkilä, Special Adviser on Quality Assurance and Safety, Health Technology and Pharmaceuticals, WHO, Geneva, Switzerland
Dr S. Kopp-Kubel, Quality Assurance and Safety: Medicines, Essential Drugs and other Medicines, WHO, Geneva, Switzerland
Mr D. Sato, Drug Management and Policies, WHO, Geneva, Switzerland
Miss M. Schmid, Quality Assurance and Safety: Medicines, Essential Drugs and other Medicines, WHO, Geneva, Switzerland
Miss A. Wehrli, Regulatory Support, Drug Management and Policies, WHO, Geneva, Switzerland
Mr Y. Yoshida, Quality Assurance and Safety: Medicines, Essential Drugs and other Medicines, WHO, Geneva, Switzerland
Acknowledgements
Acknowledgement was made by the WHO Secretariat to the following people, for their valuable contributions to the discussions: Miss M. Cone, International Federation of Pharmaceutical Manufacturers Associations (IFPMA), Geneva, Switzerland; Dr I. Kanfer, International Generic Pharmaceutical Alliances, Genpharm Inc., Etobicoke, Ontario, Canada; and Dr R. Patnaik, Deputy Director, Division of Bioequivalence, Center for Drugs Evaluation and Research, Food and Drug Administration, Rockville, MD, USA.
References
1. Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations, Thirty-fourth report. Geneva, World Health Organization, 1996, Annex 9 (WHO Technical Report Series, No. 863).
2. The use of essential drugs. Eighth report of the WHO Expert Committee (including the revised Model List of Essential Drugs). Geneva, World Health Organization, 1998 (WHO Technical Report Series, No. 882).
3. The international pharmacopoeia, 3rd ed. Vol. 1. General methods of analysis; Vol. 2. Quality specifications; Vol. 3. Quality specifications; Vol. 4. Tests, methods, and general requirements. Quality specifications for pharmaceutical substances, excipients, and dosage forms. Geneva, World Health Organization, 1979-1994.
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