International Nonproprietary Names for Pharmaceuticals and Internet Domain Names
Sabine KOPP-KUBEL <email@example.com>
WHO has a constitutional mandate inter alia to "develop, establish and promote international standards with respect to biological, pharmaceutical and similar products."
WHO collaborates closely with national nomenclature commissions to select a single name of worldwide acceptability for each active substance that is to be marketed as a pharmaceutical. Some 7000 international nonproprietary names (INNs) have been published since 1950.
To avoid confusion, which could jeopardize the safe use of medicines by patients, nonproprietary names should not be used in Internet domain names.
WHO has a constitutional responsibility to "develop, establish and promote international standards with respect to biological, pharmaceutical and similar products" (Article 2(u) of WHO's Constitution).
This is the basis for many activities within WHO, such as International Nonproprietary Names (INNs), WHO Good Manufacturing Practices, the International Pharmacopoeia, and many others. The program was established in 1950 and some 7000 names have been published to date.
The section of the WHO specifically dealing with selection of International Nonproprietary Names for pharmaceutical substances falls under the Division of Drug Management and Policies.
Most products available on the market are nowadays advertised, promoted, and identified by a trade name. This is also true in the pharmaceutical field. In many countries trade names, also called trademarks or brand names, are used when prescribing, dispensing, selling, promoting, or buying a medicament. Trade names are usually selected by the owner of the product and registered in national trademark or patent offices. They are private property and can be used only with the consent of the owner of the trademark.
In most cases brand names are chosen for a finished pharmaceutical product, i.e., for one or various active drug substances in a defined dosage form and formulation. Therefore, pharmaceutical preparations containing the same active drug substance are frequently sold under different brand/trade names, not only in different countries, but even within the same country.
Fig. 1. Various trade names for one substance (example: paracetamol)
Nonproprietary names, also called generic or common names, are intended to be used as public property without restraint, i.e., nobody should own any rights on their usage. These names are usually designated by national or international nomenclature commissions.
Although both nonproprietary names and trade names may appear similar in form to an outsider, there is, in fact, a big difference. First, nonproprietary names are designations to identify the active pharmaceutical drug substance rather than the final product. Second, the selection of a nonproprietary name follows established rules so that the name itself communicates to the medical and pharmaceutical health professional the therapeutic or pharmacological group to which the active drug substance belongs.
The rapid industrial development in the beginning of this century has resulted in the development of a large number of synthetic drug substances. Before, most of the products used were of natural origin and known by simple trivial names. The introduction of synthetic substances provided the opportunity for patent protection and the use of trademarks. These short names were attractive since compounds could otherwise only be described by a systematic or chemical name. A systematic chemical name may be developed following the guidelines of international bodies, including the International Union for Pure and Applied Chemistry (IUPAC). However, these names were usually long and difficult to retain. Therefore national nomenclature bodies and the international nomenclature program were formed to develop simple generic names of public property
Fig. 2. Various common names used for one substance (example: paracetamol)
The INN program was started in 1950 when Member States passed a resolution at the World Health Assembly. It falls also under WHO's constitutional mandate of setting norms and standards for pharmaceutical products.
A procedure for the selection of recommended international nonproprietary names for pharmaceutical substances was developed together with general principles for guidance in devising INNs for pharmaceutical substances.
In the beginning of WHO's program, the experts coordinated the activities of existing national nomenclature bodies. Many substances had already well established names, e.g., acetaminophen/paracetamol. A single name had to be chosen.
Naming of new substances was coordinated from the start in order to have only one single name worldwide in future. Secretaries or representatives of all major national nomenclature committees, such as France, Japan, the United Kingdom, and the United States, are practically ex officio members of the INN Committee.
Fig. 3. INNs -- the key to one name worldwide
This approach has proven successful in that it ensures that national and generic names are identical.
Fig. 4. One International Nonproprietary Name (INN) for one substance in different languages (example: paracetamol)
How are INNs selected? A request for an INN is usually submitted on a form (INN application form: WHO 5233 (89/90)-1000) to the World Health Organization. In certain countries, where national nomenclature commissions exist, this is done through the corresponding national nomenclature authority; e.g., in the United States it is the United States Adopted Names (USAN) Council.
Precise information on the chemistry, pharmacological action, and use, as well as suggested nonproprietary names and name and address of the manufacturer, are to be provided on the form.
Each name proposed by the originator of such a request is then examined and a name selected. All members of the WHO Expert Panel on the International Pharmacopoeia and Pharmaceutical Preparations designated to select nonproprietary names have to agree to the name which is then first published as a proposed INN. During a four-month period, any person can forward comments or lodge a formal objection to a name, e.g., on grounds of similarity with a trade name. If no objection is raised, the name will be published a second time as the recommended INN.
The primary principles for selection are that an INN should be
The INN for a substance belonging to a group of pharmacologically related substances shows the relationship by the use of a common stem.
The following may serve as an example of how INNs are composed. Usually an INN consists of a random, fantasy prefix and a common stem. Sometimes substems are established to differentiate between different related groups of substances.
Examples of some common stems are as follows:
stem: used for ...
-ac: anti-inflammatory agents, ibufenac derivatives;
-azepam: diazepam derivatives, anxiolytics, sedatives;
-olol: beta-adrenoreceptor antagonists, anithypertensives; and
-mab: monoclonal antibodies.
Examples of some INNs in the above series:
prefix : substem : stem --> INN
alpren : - : olol --> alprenolol
clon : - : azepam --> clonazepam
di : - : azepam --> diazepam
ibu : fen : ac --> ibufenac
propran - olol --> propranolol
vo : tum u : mab --> votumumab
In the series of INNs ending in -azepam, some 50 names have been published to date; in the series of -olol, there are almost 100 substances for which INNs have been published.
In addition to the above rules, certain rules have been established to allow the use of INNs internationally, i.e., in various languages. For example, the letters "h" and "k" should be avoided; and "e" should be used instead of "ae" and "oe," "i" instead of "y" and "t," and "f" instead of "th" and "ph."
All newly selected names are published, after informing the originator of the request, in the journal WHO Drug Information which is published by the division of Drug Management and Polices (DMP) - WHO.
Two proposed and two recommended lists are published per year. The lists are trilingual, in English, French, and Spanish, including also Latin INNs. In addition, a Russian version is published in the Cumulative list of INNs, which is updated periodically. At present some 7000 INNs have been published.
Nonproprietary names are intended to be used in
Since the beginning of the INN Program in 1950, the WHO Member States have foreseen that the protection of INNs was very important and that the issue was complex (EB7.R79, WHA6.15, WHA46.19).
During the past few years, INN common stems have been increasingly introduced in trademarks. This hampers the selection of new nonproprietary names within the established system. Given the fact that all INNs should be distinct from existing INNs and trademarks, this practice causes difficulties when selecting a new name. In addition it causes confusion to health professionals and may be the source of serious errors in prescribing and dispensing.
Based on recommendations made by the WHO Expert Committee on the Use of Essential Drugs, a resolution was adopted during the 46th World Health Assembly requesting Member States to
The one very novel generic name issue which has arisen with the use of the World Wide Web is the issue of domain names. By their nature, domain names are unique indicators which identify the address for the home page of any given Web page. In addition, a domain name acts as a memorable way for people to access any given Web site. It is, therefore, not only an address but also a specific identifier.
At first one body was created for coordinating use of the Internet on a worldwide basis, i.e., one center has been responsible for the official registry for domain names on the Internet. With the growing demand, regional registries have been set up. With the splitting of registries to regional and country-specific types, the issue became even more complex.
The registration of domain names has to be seen as rather distinct from the registration of trademarks or the selection of International Nonproprietary Names for pharmaceutical substances. In the beginning the checks made by the domain name registries have been rather basic, since their main interest was to ensure that domain names registered were unique, as this was the only technical requirement for the Internet. The rules have thus mainly included provisions to eliminate duplicate applications.
Over time, various registries have, however, developed rules providing that they will not register domain names where the applicant is clearly commercially not entitled to use a name. Recently a number of domain name registries have developed some form of dispute policy and rules relating to what can be registered or not.
The major points addressed in this policy statement include the following:
At the international level, attempts have been undertaken recently by the various parties involved in the registration of domain names to describe a domain name dispute resolution procedure for worldwide applicability.
WHO's division of Drug Management and Policies, along with the WHO Legal department, collaborates with colleagues in the World Intellectual Property Organization (WIPO) in the protection of INNs against misuse as domain names on the Internet. Attempts are under way to provide the possibility of challenging registration of a domain name on the basis that the second level domain name is identical, or substantially identical, to an INN published by the World Health Organization (WHO).
The underlying reason for ensuring that no party can claim any proprietary rights in INNs is to protect the safety of patients by allowing them to identify a specific pharmaceutical substance under one single, globally available name.
1. Basic Documents, Thirty-ninth edition, World Health Organization, Geneva, Switzerland, 1992
2. Forty-sixth World Health Assembly Resolution on Nonproprietary Names for Pharmaceutical Substances (WHA46.19), World Health Organization, Geneva, Switzerland, 1993.
3. Examples of published INN lists: List 77 of proposed INNs: WHO Drug Information, 1997, 11(2); List 38 of recommended INNs: WHO Drug Information, 1997,11(3); List 78 of proposed INNs: WHO Drug Information, 1997, 11(4); World Health Organization, Geneva, Switzerland
4. Cumulative List No. 9 of International Nonproprietary Names (INN) for Pharmaceutical Substances, World Health Organization, Geneva, Switzerland, 1996.
5. Guidelines on the Use of International Nonproprietary Names (INN) for Pharmaceutical Substances (WHO/PHARM S/NOM 1570)
6. The use of common stems in the selection of international nonproprietary names (INN) for pharmaceutical substances (WHO/PHARM S/NOM 15) [updated regularly]
7. Request form for an International Nonproprietary Name (INN) [form also available on the Internet: http:/WWW.WHO.CH/programmes/dmp/innmain.htm]
8. Procedure for the selection of recommended international nonproprietary names for pharmaceutical substances (in English, French & Spanish)
9. General principles for guidance in devising international nonproprietary names for pharmaceutical substances (in English, French & Spanish)
10. Kopp-Kubel S. Dr., Update/Le point - International Nonproprietary Names (INN) For pharmaceutical substances, Bulletin of the World Health Organization, 1995, 73 (3): 275-279.