International Nonproprietary Names LLOYD C. MILLER
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United States Pharmacopeia, New York 16, Ν. Y. A program for selecting nonproprietary names for drugs through international cooperation is conducted by the World Health Organization, with its object being to minimize the discrepancies in common names for drugs existing between nations. The organization of the project and progress as well as fundamental and controversial difficulties are discussed.
A chemist's success i n conceiving and synthesizing a new compound which proves valuable as a drug not only opens great opportunities scientifically but also imposes weighty responsibilities. These remarks are directed to singling out the responsibil ities concerned p a r t i c u l a r l y w i t h pharmaceutical nomenclature. It is important that each new d r u g come on the market w i t h two unique names. One of these is the brand or trade name, which should be registered for the exclu sive use of the interested firm. Such a name is deemed to be better i f it is easily recognized and remembered. The second name is the t r i v i a l or nonproprietary name, which need not have the qualities desirable i n a brand name but should i n d i cate something of the chemical nature of the drug. While this is a nonproprietary name, available for free and unrestricted use, i t too may be registered. F r e quently, however, the struggle of finding the brand name is so exhausting that no serious effort is made to find a nonproprietary name at first. This failure invites future trouble, the most serious kind of which is the possibility that the brand name w i l l come into such common use as to lose its exclusive, protected status. The best known examples of this are the names aspirin and cellophane. F r o m the standpoint of the world market i n drugs another source of difficulty looms larger. It resides i n the probability that different nonproprietary names w i l l come into use for the same drug. The resulting confusion benefits no one and is a nuisance i n drug commerce. It means that, i n the face of a multiplicity of trade marks, the one possible common key to identity is lost. The greatest confusion is i n the hindrance to the interchange of scientific information, both experimental and clinical. The complications of abstracting and cataloging are also serious. F i n a l l y , differences i n nonproprietary nomenclature can only result i n a higher cost of doing business. The only means of avoiding multiplicity i n nonproprietary nomenclature for drugs is through international action, i n spite of a l l the obstacles that obstruct the paths i n that direction. The problem bears on public health generally, so that the W o r l d Health Organization has undertaken to bring about order and uniformity on a n international scale. A s a unit of the U n i t e d Nations and the successor to the Health Organization of the League of Nations, the W H O alone is i n a logical position to assume this role. It may be debatable whether the menace to world health from confusion over drug nomenclature is to be ranked w i t h such pressing problems facing the W H O as the eradication of tuberculosis, malaria, and other deadly diseases. Furthermore, the funds of W H O are limited. The fact is, however, that W H O has established a program aimed at recommending, for international adoption, a single, nonproprietary name for each drug likely to move i n international commerce. In 1955, an arrangement was completed for naming compounds capable of producing addiction even though they may not have been introduced commercially as drugs. This action facilitates the important task of the United Nations body responsible for the international control of traffic i n narcotic agents. Program of World Health Organization
A rather f u l l discussion of the mechanics of the program has been published (1, 2, Jt-6). Briefly, the project i s directed by the W H O Secretariat i n Geneva, Swit38
A Key to PHARMACEUTICAL AND MEDICINAL CHEMISTRY LITERATURE Advances in Chemistry; American Chemical Society: Washington, DC, 1956.
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MILLER—INTERNATIONAL
NONPROPRIETARY
NAMES
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zerland, w i t h the advice of a Subcommittee on International Nonproprietary Names consisting of four individuals, from areas of the world having a very real interest in the subject. U n t i l recently these four were: Hans Baggesgaard-Rasmussen, R o y a l Danish School of P h a r m a c y ; Rene H a z a r d , School of Medicine, U n i v e r s i t y of P a r i s ; C. H . Hampshire, retired secretary of the B r i t i s h Pharmacopoeia Com mission; and the writer. In 1953, Robert T. Stormont, secretary of the Council on Pharmacy and Chemistry of the American Medical Association, replaced the writer on the subcommittee. A s w i t h a l l W H O experts, these serve on a voluntary basis without pay. In the United States, coined, common names for drugs are usually spoken of as "generic" names but this practice is not followed elsewhere. Hence, the W H O chose the term, nonproprietary, instead of generic, to designate names not covered by trade-mark rights. Since p r i m a r i l y the word "generic" means classification according to genus and genera, there is no doubt that "nonproprietary" is a more specific and less ambiguous term, although less convenient. Specificity is a highly desirable attribute, considering especially the necessity for translation into several languages. Since L a t i n is still regarded as the universal language of medicine and pharmacy, the p r i m a r y form of the international nonproprietary name is L a t i n w i t h the E n g l i s h and French equivalents given secondarily i n parallel i n a l l W H O publications. The program was established i n 1950 and the subcommittee set up rules of nomenclature patterned almost exactly after those followed by the Council on Pharmacy and Chemistry of the A m e r i c a n Medical Association and the B r i t i s h Pharmacopoeia Commission. These rules have been published and are generally known ; they are considerably more flexible than those of the Scandinavian P h a r m a copoeial Council which adopts names for use i n the four Scandinavian countries and Iceland. Not until 1953, did the American pharmaceutical industry take an active interest in the W H O program, although three years earlier the A m e r i c a n D r u g Manufac turers Association had given i t enough attention to pass a resolution upon i t . This earlier action was not recalled d u r i n g the protest campaign which ultimately reached the floor of the W o r l d Health Assembly i n its annual session i n M a y 1953. The result was a very beneficial re-examination of the entire program with a restate ment of its aims and procedures, which h a d evolved piecemeal i n the first 3 years of the program's operation. The protest campaign was spearheaded by the two leading trade associations of the pharmaceutical industry, the American D r u g Manufacturers Association and the American Pharmaceutical Manufacturers Association, which enlisted the sup port of other organizations including the United States Pharmacopeia. The com plaint was on the grounds that there was insufficient opportunity for drug houses to comment on proposed names and that no procedure was established for appealing decisions i n these cases where the name adopted by the W H O was deemed objection able or detrimental to trade-mark rights. These complaints were unquestionably justified. N o t only was the program inadequate but its operation on an informal plane was simply not compatible with the magnitude of the interests concerned. Some of the drugs on which agree ment was not readily reached had a business volume r u n n i n g into tens of millions of dollars a year, as i n the case of Terramycin which came out with oxytetracycline as its international nonproprietary name. Structure of World Health Organization
The lack of opportunity to comment on proposals was directly related to the organizational structure of the W H O . The body is set up to maintain contact w i t h each of the member states, the 81 nations of the world which have f u l l or associate membership, through the respective official correspondents, generally the Ministers of Public Health or as here, the Surgeon General of the U . S. Public Health Service. Suggestions, complaints, and appeals for W H O assistance a l l channel i n through these correspondents. The Director-General of W H O is guided i n responding to many of these communications by experts who advise i n a completely independent capacity according to their best individual judgments. Their recommendations then flow out from W H O through the same official correspondents. This means that for A Key to PHARMACEUTICAL AND MEDICINAL CHEMISTRY LITERATURE Advances in Chemistry; American Chemical Society: Washington, DC, 1956.
A D V A N C E S IN CHEMISTRY SERIES
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each country, a l l nationals, private citizens, and multimillion-dollar d r u g firms alike are expected to be kept informed mainly over a single line of communication. W i t h nonproprietary names for drugs, the proposals were being received freely enough but movement i n the opposite direction left much room for improvement. D r u g firms were not learning that names were being sought for their products until the process of selection had gone too f a r for lodging protest. N o clear avenues of appeal had been provided. F u r t h e r , the whole area is one i n which little inter national law has yet been established. Special measures were taken to circulate the proposed names regularly through the Bulletins of the Combined Trade-Mark Bureau. It proved that the American pharmaceutical industry was not alone i n benefiting from this publication of the W H O proposals. A t least two trade papers reprinted them as news items and the effectiveness of this publicity was attested b j comments received here from as f a r away as Holland and A u s t r a l i a . A l l such comments were forwarded to the W H O Secretariat i n Geneva f o r transmission to the other members of the Subcommittee on International Nonproprietary Names. Nevertheless, the American drug industry felt that this relatively prompt but informal system was inadequate and unfortunately no effort was made elsewhere i n the world to duplicate it. The procedure now i n effect calls for even more extensive publication of the names i n the American pharmaceutical press. F u r t h e r , some restrictions have been laid down and an appeal process is spelled out. Procedure for Proposals of Nonproprietary Names
In brief, the new procedure calls for submitting proposals for Recommended International Nonproprietary Names on a regular form to W H O as i n the past. The proposals are forwarded from the Secretariat i n Geneva to the subcommittee for consideration w i t h the understanding that the original name shall be accepted unless there are "compelling reasons to the contrary." The rules adopted i n 1954 embody important changes i n the original rules: The clause ". . . unless there are compelling reasons to the c o n t r a r y " is employed i n connection w i t h adopting the name coined by the person discovering or first developing the drug i n question. There remains room for debate as to what con stitutes a "compelling" reason but obviously t r i v i a l reasons a r e ruled out. The greatest potential source of difficulty arises i n this connection from the differences in attitude toward nonproprietary names existing between nations. In the United States no special pressure has been exerted i n the past to select names that w i l l have a reasonable chance of competing w i t h the brand name for the same drug. Elsewhere, p a r t i c u l a r l y i n E n g l a n d and Denmark, a great deal of attention is given to adopting nonproprietary names as short and euphonious as brand names gen erally are. Names under consideration are to be published i n the Chronicle of the World Health Organization (3). A 4-month period is allowed for submitting comments or protests from the time of publication. Considering the Chronicle is i n press some 2 months before i s sue and that the subcommittee w i l l require time both before and after the 4-month w a i t i n g period, the minimum time needed for establishing a name w i l l be about one year. Certainly no manufacturer w i l l want to hold his product off the market for a year pending the W H O action i n those countries of Europe and South A m e r i c a where each d r u g must bear an accepted nonproprietary name. Proprietary names are generally three syllables i n length, whereas i t is rare f o r a nonproprietary name to be less than four syllables. In the case of 35 U . S . P . X I V drugs which are under patent control or exclusively marketed by a single firm under its trade name, the average syllable length of the U . S . P . title is 4.1, whereas the corresponding trade-marks average 3.2 syllables. In only one instance, Neo-Syneph-' rine vs. phenylephrine, is the protected name the longer of the two. The great emphasis placed on t a k i n g the nonproprietary name first put into use by the individual or firm developing a d r u g makes i t obvious that the i n i t i a l selection demands careful attention to the guiding principles of d r u g nomenclature established by the W H O . Those who have dealt with the A . M . A . Council on P h a r macy and Chemistry i n the past w i l l recognize most of them. They are set forth here i n the interest of completeness:
A Key to PHARMACEUTICAL AND MEDICINAL CHEMISTRY LITERATURE Advances in Chemistry; American Chemical Society: Washington, DC, 1956.
M I L L E R — I N T E R N A T I O N A L NONPROPRIETARY
NAMES
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General Principles for Guidance in Devising International Nonproprietary Names
1. Names should, preferably, be free from any anatomical, physiological, pathological, or therapeutic suggestion. 2. A n attempt should first be made to form a name by the combination of syllables i n such a w a y as to indicate the significant chemical groupings of the compound and/or its pharmacological classification. Preference should be given to the following syllables : Latin English Type of Compound -inum -ine F o r alkaloids and organic bases -inum -in F o r glycerides and neutral principles -olum -ol F o r alcohols and phenols ( - O H group) -alum -al F o r aldehydes -onum -one F o r ketones and other substances containing the CO group -enum -ene F o r unsaturated hydrocarbons -anum -ane F o r saturated hydrocarbons -cainum -caine F o r local anesthetics -mer -mer F o r mercurial compounds -sulfonum -sulfone F o r sulfone derivatives -quinum -quine F o r a n t i m a l a r i a l substances containing a quinoline group -crinum -crine F o r antimalarial substances containing an acridine group -sulfa -sulfa F o r derivatives of sulfanilamide -dionum -dione F o r antiepileptics derived from oxazolidinedione -toinum -toin F o r antiepileptics derived from hydantoin -stigminum -stigmine F o r anticholinesterases 3. Names should be distinctive i n sound and spelling. They should not be inconveniently long and should not be liable to confusion w i t h names already i n use. 4. The addition of a terminal capital letter or number should be avoided as f a r as possible. Chemists w i l l recognize some ambiguity i n Item 7, especially for those com pounds which may be looked upon as f a l l i n g into more than one group. Furthermore, the task of finding distinctive combinations of syllables having some relation to the chemical structure becomes more difficult year by year as the simple groupings are exhausted and the chemical nature of the drugs becomes so much more complex. The first tendency would be to take a path of least resistance and to choose names without regard to length and euphony. Two forces operate against this choice. F i r s t , there is the above-mentioned jeopardy to the protected trade-marked name i f it is very much easier to use. Second, the movement among physicians and phar macists to use the official names of drugs is gaining strength. A s this movement picks up impetus, a greater and greater area becomes a fertile ground i n which resentment against long, awkward names can sprout and flourish. The chemist of the drug industry is i n a strategic position to prevent this resentment by using judicious care i n selecting nonproprietary names which w i l l be wholly suitable for international use. Such efforts might be likened to using a preemergent weed-killing spray, which stops trouble before i t gains headway. F i n a l l y , there are bound to be cases when the nonproprietary name first pro posed w i l l not prove suitable internationally even though i t has come into f a i r l y general use i n some one country. A prime example is the fact that the names of a l l of the chemical elements are not yet settled. When such cases arise i t is to be hoped that a l l concerned w i l l take an open-minded attitude conducive to working out a compromise i n a spirit of true international cooperation. Literature Cited
(1) Blanc, P., Bull. fed. intern, pharm., 24, 138 (1950/51); Chronicle of World Health Organization, 6, 322-6 (1952). "International Nonproprietary Names for D r u g s , " summary of lecture by P. Blanc, Secretary, E x p e r t Committee on International Pharmacopoeia, 14th General Assembly, International [Pharmaceutical F'ederation (2) H o r a n , J . J . , Ibid., 43, 657-74 (1953). Revised W H O P r o g r a m on Generic Names. (3) International Nonproprietary Names, Chronicle of World Health Organization, 7, 41-8 (1953). (4) Ibid., 7, 297-324 (1953). (5) Levy, M . W., Ibid., 43, 229-41 (1953). W H O Authorized It? (6) M i l l e r , L . C , Trade-Mark Reporter, 43, 133-62 (1953). International N o n proprietary Names.
RECEIVED
September
13,
1954.
A Key to PHARMACEUTICAL AND MEDICINAL CHEMISTRY LITERATURE Advances in Chemistry; American Chemical Society: Washington, DC, 1956.
