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"6. That funds be sought to make possible the wider distribu
tion of FDA reports and bulletins, that programs be developed for the training of FDA and other Food and Drug personnel, and that the participation of FDA scientists in scientific meetings and the preparation of scientific papers be encouraged."
I concur in the objectives of this recommendation. I
"VERY serious student of medicine well know's
course of his schooling to include, with respect to human anatomy alone, the names of some 200 bones, hundreds of nerves, muscles, and vessels, and dozens of organs. Quite providently, evolution proceeds slowly enough for this store of information to remain fairly fixed and constant for the student of any given generation. This is not so, however, for the host of drugs which he must learn to know by name, to say nothing of identity, action, and use.
What perplexes students and practicing physicians alike is why these drugs must be known by seldom fewer than 3, usually 4, and often more than a half-dozen different names. And those who go abroad for study find themselves obliged to learn still other names in use there for familiar drugs. These comments explore this baffling situation and will perhaps dispel some common misunderstandings, especially with respect to nonproprietary
The multiplicity of names for drugs is inevitable. In addition to the systematic chemical name for a given drug there are the trivial names by which it may be known familiarly among chemists, the code number needed during research and development, the proprietary names nccded when the drug is sold, and the generic name that is used as the common designation for all the various brands. The generic name, which is nonpropric. tary, is usually chosen by concerted action of representatives of manufacturing, med. ical, and governmental organizations. The medical professio. :ould cooperate in the effort to minimize confusion hy using accepted nonproprietary names.
The Five Categories of Drug Names On its way to a place in therapeutics, a medicinal compound acquires names or designations that fall into 5 categories. When first synthesized, or when first identified if derived from a natural source, a. potentially useful compound receives a systematic chemical name. To be adequate and fully specific, this name must reveal every part of the compound's inolecule, including any and all forms of isomerism if present, and must be such that it can describe only the compound concerned and no other. The systematic chemical name is generally so formidable that even chemists, especially those concerned with the synthesis of organic medicinal compounds, have little patience with it and tend to coin “trivial” names to abbreviate the names for specific compounds or groupings. Althongh examples of trivial names are numerous, citing one suffices to illustrate the adv.intages of their usc. Chemically, phenol is hydroxybenzene or hydroxycyclohexatriene; yet how many recoynizi at once that the "trivial" name and the 2 systematic names are synonymous?
Rather interesting stories lie behind the selection of some trivial names, as in the case of barbituric acid. This was the discovery of the chemist, Baeyer, who canie upon the new compound as a combina. tion of maleic acid with a breakdown product of Director of Hevision, U. S. Pharmacopeia.
uric acid. He wrote later that he was enamoured at the moment of a charming lady named Barbara, and so he decided to call the new compound “barbituric acid” in her honor. The story does not end there, for later the physician von Mehring took a trip to Italy shortly after discovering the hypnotic properties of diethylbarbituric acid, and, as he approached the city of Verona, he was struck with the idea of naming this compound Veronal. But for the development of newer barbiturates, this name would still be in use as a brand name for diethylbarbituric acid.
For the same reasons that chemists turn to trivial names as a shorthand form of chemical designation, their colleagues, the pharmacologists and others, often identify new compounds during their study in the laboratory by coile numbers, which are usually preceded by a common prefix distinctive of the Jaboratory in which the work is being done. This logical practice probably antodates Ehrlich, who, however, made it famous about 50 years ago when he numbered the compounds during his scarch for the "magic hullet” to cure syphilis. Thus, lis compound 606 is probably better known by number than by the naine arsphenamine or Salvarsan. Recently, another laboratory code number, MER/29. became so well known that it was adopted as the registered trademark for the anticholesterolemic drug concemned (triparanol). If used, a compound's code number stays with it through the laboratory study and frequently through the clinical investigation. While there is little need to identify the code number with the respective chemical name of the compound in the earlier stages, there is good reason for having it call to mind the laboratory that employs it. (This point is treated more fully in a subsequent section.) When used in scientific publications, the code number must be ably identified as a matter of scientific specificity.
When tests show that the compound has real utility for therapeutic purposes and the investigation justifies offering it for sale, a proprictary name is necded. Known also as the trademark, since it is. registered as such with the United States Patent Office, this name identifies the specific brand of the compound with the firm that owns the mark. As a rule, this is the firm that has borne the expense of synthesizing the compound (which finally may now be called a drug) and of carrying out the laboratory and clinical tests, to say nothing of bearing the cost of producing it in sufficient quantities for wide distribution and making its virtues known to physicians. This proprietary name is therefore the exclusive, and ofttimes very valuable, property of the firm with which it is identified. It is incorrect to speak of it as the "trade name" which, under trademark law, is synonymous with the company name.
At this stage there also appears the generic or nonproprietary name. These two terms are regarded as synonymous, yet they differ in ways that Stecher' has clearly distinguished:
The adjective generic obviously comes from the Latin word genus and suggests classification into genera as is the practice in botany and zoology. Actually the term is a misnomer as used in the drug field. The generic name does not relate to a class or genus of drugs; it denotes a single drug. Generic here is taken as opposed to specific. Specific applies to the trademark (also called brand or proprietary name) which is specific to one sole owner, while the generic name is nonproprietary. The term nonproprietary is more accurate and descriptive, but generic sounds better, is shorter and easier to pronounce-and so will probably stay with us for a long time to come, although it is a contradictory term. It most decidedly does not describe a genus or kind of products common to all the pharmaceutical trade. It does denote or should denote a unique substance definable in chemical nomenclature as a single chemical compound not to be confused with any other substance of the samo kind or belonging in the same group of drugs. This definition has been broadened to allow the coining of generic names for natural aggregates of substances such as extracts of plant or animal origin, but excludes proprietary mixtures where each component has its own generic name.
Not only is the term “generic” misapplied, but actually it is needed in drug nomenclature in its true meaning, i.e., as a designation for families of active compounds. Thus, vitamin A is the true generic name for a family of at least 4 closely related compounds having vitamin A activity. Similarly, vitamin D and vitamin B12 are true generic names for the families of vitamin D compounds and vitamin B 2 compounds.
But the term “generic" has recently acquired an economic aura or aroma, depending upon the point
of view, that rather spoils its utility for designating a class of drug names. Actually, by curious accident, a new and appropriate usage of “generic” has sprung up in the sense that today it is used to designate collectively the several brands of a given drug that are marketed by several firms; that is, the various brands of a single dng may be regarded as a family or genus of products, and their respective nonproprietary names are “generic” as a group. However, the term “nonproprietary” deserves adoption until something more suitable is proposed, because its specificity outweighs its unwieldiness.
One final class of names remaining to be discussed consists of the official titles used in the U. S. Pharmacopeia and the National Formulary. With rare exceptions, these are the nonproprietary names that have been used during the period of establishing the drug's place in rational therapy. An example of the kind of changes made by the U.S.P. Committee of Revision is the U.S.P. title Chlorpheniramine Maleate, which represents a slight condensation of the longer nonproprietary name chlorprophenpyridamine maleate. The latter name was in use for some time before the drug was recognized in the Pharmacopeia.
At this time, proposals are pending before Congress (H.R. 6245 and S. 1552) to make the Food and Drug Administration responsible for selecting nonproprietary ("official") names for drugs and for reviewing periodically U.S.P. and N.F. titles with a view to changing them in the interest of simplicity and usefulness." While there is little on which to base a prediction on how such a law would operate if enacted, sound arguments can be marshalled for the view that no new law is needed, at least not until some use has been made of the present law to accomplish the desired end. It is patently clear that only a little cooperation on the part of all concerned would bring about marked improvement. It would seem that much would be accomplished if the Food and Drug Administration simply required, as a matter of safety, that the labeling of all new drugs subject to New Drug Applications should employ either the U.S.P. or N.F. name, if there is one, or ascertain what "common or usual name" has been established and require that it be used. Wilson notes several cases in which 2 or more names have been used for a single drug.
Finally, with respect to the review, the record of the past supports 2 statements with considerable certainty. First, experience has shown that changes in U.S.P. or N.F. titles cause so much confusion that it is unlikely that the Food and Drug Administra. tion would suggest much, if any, alteration in existing titles. Second, if the proposed system were to be put into operation, it is quite unlikely that either the U.S.P. or N.F. Committees of Revision would select titles that differed from those chosen by the Food and Drug Administration. This is not to say that the U.S.P. Committee of Revision has approved all titles chosen by a government agency in the past, since the Committee considered some of the names assigned to biological products by the National Institutes of Health unsuitable for U.S.P. titles. Two examples of the few cases in which the U.S.P. title differs from the N.I.H. name (the former listed first) are: Human Blood Cells vs. Packed Red Blood Cells (Human) and Normal Human Serum Albumin vs. Normal Serum Albumin (Human).
The Need for Nonproprietary Names Not all therapeutic agents are the object of mutiple naming. Those that are common household chemicals generally have the fewest names, yet the common and simple substance “sugar” is listed in the Pharmacopeia as “sucrose," and, as a 12-carbon disaccharide, it has a rather formidable chemical name. Perhaps no compound has simpler nomenclature than U.S.P. Sodium Chloride, which has long been known simply as “salt.” Here is an instance where an ancient name of a single com. pound was appropriated as a truly generic name for a large chemical class of compounds known as salts. Various brands of sodium chloride are sold as "... Brand of Tablet Salt.”
In cases in which the same medicinal compound is available from a considerable number of firms, as in the case of isoniazid, a really complex situation exists. The drug is well known also by its trivial chemical name, isonicotinic acid hydrazide. At one time, this . tuberculostatic drug was available from as many as 25 different firms, almost all of which had coined their own brand names, but isoniazid, the U.S.P. title, was the one name in common for all the various brands. Therefore, if for no other reason than as a common bond of identity in the market place, nonproprietary names are needed.
But there is another reason, much more cogent from a manufacturer's standpoint, in that nonproprietary names serve to protect trademarks. The federal law governing the granting and use of trademarks, the Lanham Act of 1946, provides that a trademark may fall into the public domain if the public adopts it as a common name. Years ago, trademark rights to the name aspirin were lost in the United States; anyone can use it here, although proprietary rights to it are still valid in some other countries.
It must be pointed out that nonproprietary names are considered only for single compounds, whether of synthetic or natural origin. While trademarks can be assigned to mixtures, only the active ingredients of such mixtures are designated by nonproprietary
name need be only adequate to protect his trademark; he has no real concem about length and unwieldiness since, once a nonproprietary name is made available, only due diligence is demanded of him to protect his trademark. This he does by using a symbol, an encircled superscript R or its equivalent, and by taking pains always to warn editors and authors who fail to follow the convention of capitalizing the initial letter of a trademark or otherwise fail to show its protected status. Diligence in this respect can offset the tendency to substitute the trademark for an impossibly unwieldy nonproprietary name.
Freedom from conflict with any other names used for drugs is an important attribute, and the manu. facturer takes pains to ascertain that the nonproprietary name, as well as his trademark, passes this test. A complaint of possible conflict gave rise to the change in pronunciation of Banthone indicated by the long “i"; the same might have been achieved by substituting a “y” but this seems not to have been considered. The manufacturer expects others to be equally painstaking, but bitter court battles have arisen when, for one reason or another, the rules of the game have been transgressed. This factor works strongly against the choice of short nonproprietary names, for the risk of conflict diminishes with length; and a long name may incorporate several syllables, any one of which taken alone would cause protest. The viewpoint of the physician, pharmacist, teacher, and general public is often neglected in debating the suitability of nonproprietary names. Since the public scarcely has an advocate to plead its case, protests from those who fear injury from conflict may weigh disproportionately heavy in the balance.
Without entering into debate on the merits of prescribing exclusively by “generic” or nonproprietary names, it is self-evident that the convenience of all is served best when the nonproprietary names are as short and pronounceable as possible. Yet there is equal agreement on the proposition that the name should point up such relationships as exist among compounds that fall into a common phar. macological group. This mitigates against brevity and, indeed, leads directly to names that have been criticized for their length. Such is the case of the group of antibiotics, the parent member of which was named tetracycline. Adoption of that name logically led to the already known chlortetracycline and oxytetracycline, both available as the hydrochloride salt. There followed, as a result of commendable research, rolitetracycline, a pyrrolidline derivative, and demethylchlortetracycline, by the removal of a methyl group from chlortetracycline. Syllable-counters have a heyday with the hydrochloride of demethylchlortetracycline particularly; yet it fits logically into the pattern of the first names chosen. In retrospect, it might have helped to have picked tecline, or tycline, or some other available
one or two-syllable name for the parent molecule; but the object at the time was to convey the newlyfound information that this compound consisted of + benzene rings which an accommodating strain of actinomyces had lined up like soldiers four-abreast in a new and exciting molecule. This discussion makes it obvious that a choice has to be made between meaningless short names and longer names that convey helpful information.
What is overlooked by those who complain that many “official names” are hard to remember is that almost any name or, indeed, a phrase of several words be indelibly imprinted on the public memory simply by expending enough money on promotion. Countless laymen can tell you at once what cigarette recently “found the secret that unlocks the favor" or what beer long ago “made Milwaukee famous”; professional men are surely no less easily impressed by the substantial amount of promotion behind popularizing trademark names for drugs. Hopefully, there is reason to believe that the joint U.S.P.-AMA nomenclature program, referred to in the next section, will contribute significantly toward making the nonproprietary names better known; however, the force of pharmaceutical promotion against which it must compete is truly awesome.
As if the complications pointed out in the foregoing paragraphs were not bad enough in choosing stem names, the situation is worsening rapidly in respect to the names of the radicals which form appendages to most drug names, an aspect taken up in a subsequent section.
Finally, a nonproprietary name constitutes only part of the name of the dosage form of the drug, the full title of which must be used in accurate prescribing. The situation is not so bad with tablets, capsules or even the sterile solution of a drug; however, for a suspension intended for oral use, the U.S.P. title is, for example, Chloramphenicol Palmitate Oral Suspension. Or, if a preparation is required for ophthalmic use and the drug is not sufficiently stable to be distributed in ready-to-use form, the full title becomes, for example, Tetracycline Hydrochloride for Ophthalmic Solution. Standard abbreviations of these long titles are not provided in this country (although such are given British physicians in the British Pharmacopoeia), and the American physician is left to his own de. vices in dealing with the irksomeness of using the long, full titles. Hence, for this reason alone it is not surprising that he uses the shorter brand names.
The AMA Service At present, as it has for a number of years, the AMA Council on Drugs, in serving both physicians and the pharmaceutical industry, acts as a clearinghouse for nonproprietary names. Proposals are received by the Council, and, as a staff operation, these are checked against existing names. It is
important to ascertain that no conflict exists between the proposal and existing trademarks or nonproprietary names. Alternatively to having the initiative come from the producer of a drug, the Council may invite proposals wi a reports on the drug appear in the literature prior to receipt of a suggested nonproprietary name for it.
When in agreement has more or less been reached through negotiation between the producer and the Nomenclature Committee of the Council on Drugs, notice of the name under consideration is sent to several other agencies known to be concerned with the selection or use of nonproprietary names. These include the World Health Organization, the U.S. Pharmacopeia, the National Formulary, and the British Pharmacopoeia Commission. A 30-day waiting period is allowed for comments before a name becomes final. Occasionally, during this period, if it is found that another name has been selected abroad for the same compound, an effort is made to settle on one or the other of the two names.
For various reasons, the AMA has not recently published lists of names selected; however, the joint program now in effect between the U.S.P. Committee of Revision and the AMA Council on Drugs will have as one of its objectives the publication of the names selected and periodic distribution of composite lists of these names in order to bring them to the attention of scientific workers.
The Role of the World Health Organization For more than 10 years the WHO has been in a position to receive proposals from national authorities on nonproprietary names and to circulate these with a view to clearing them ultimately for international use. The WHO has no authority to require the use of these names but simply recommends that they be adopted as the only nonproprietary names for the compounds concerned. An equally important role of the WHO is to urge the national authorities to turn down private petitions for trademarking any of the names as a means of insuring that they will be kept in the public domain. The object is to have all international nonproprietary names freely avail. able to everyone everywhere.
Like the AMA Council on Drugs, the WHO confines its considerations to individual compounds or natural principles. More than 1,000 proposals have been received by the WHO since the program was established in 1950. Of these, about 800 have ad. vanced to the stage of Proposed International Nonproprietary Names and have been published at intervals in the World Health Chronicle. Inasmuch as these totals include many names that have long been established at the national level, it must not be concluded that new drugs are introduced at the rate of even 80 per year. Indeed, it is likely that the true rate is about 50 new drug entities annually. A composite list of the names proposed by the WHO has recently become available.