Guidance on INN
International Nonproprietary Names (INN) identify pharmaceutical substances or active pharmaceutical ingredients. Each INN is a unique name that is globally recognized and is public property. A nonproprietary name is also known as a generic name.
Guidelines on the Use of INNs for Pharmaceutical Substances (1997)
The INN system as it exists today was initiated in 1950 by a World Health Assembly resolution WHA3.11 and began operating in 1953, when the first list of International Nonproprietary Names for pharmaceutical substances was published. The cumulative list of INN now stands at some 7000 names designated since that time, and this number is growing every year by some 120-150 new INN.
Since its inception, the aim of the INN system has been to provide health professionals with a unique and universally available designated name to identify each pharmaceutical substance. The existence of an international nomenclature for pharmaceutical substances, in the form of INN, is important for the clear identification, safe prescription and dispensing of medicines to patients, and for communication and exchange of information among health professionals and scientists worldwide.
As unique names, INN have to be distinctive in sound and spelling, and should not be liable to confusion with other names in common use. To make INN universally available they are formally placed by WHO in the public domain, hence their designation as "nonproprietary". They can be used without any restriction whatsoever to identify pharmaceutical substances.
Another important feature of the INN system is that the names of pharmacologically-related substances demonstrate their relationship by using a common "stem". By the use of common stems the medical practitioner, the pharmacist, or anyone dealing with pharmaceutical products can recognize that the substance belongs to a group of substances having similar pharmacological activity.
The extent of INN utilization is expanding with the increase in the number of names. Its wide application and global recognition are also due to close collaboration in the process of INN selection with numerous national drug nomenclature bodies. The increasing coverage of the drug-name area by INN has led to the situation whereby the majority of pharmaceutical substances used today in medical practice are designated by an INN. The use of INN is already common in research and clinical documentation, while their importance is growing further due to expanding use of generic names for pharmaceutical products.
Use of INN
Nonproprietary names are intended for use in pharmacopoeias, labelling, product information, advertising and other promotional material, drug regulation and scientific literature, and as a basis for product names, e.g. for generics. Their use is normally required by national or, as in the case of the European Community, by international legislation. As a result of ongoing collaboration, national names such as British Approved Names (BAN), Dénominations Communes Françaises (DCF), Japanese Adopted Names (JAN) and United States Accepted Names (USAN) are nowadays, with rare exceptions, identical to the INN.
Some countries have defined the minimum size of characters in which the generic nonproprietary name must be printed under the trade-mark labelling and advertising. In several countries the generic name must appear prominently in type at least half the size of that used for the proprietary or brand-name. In some countries it has to appear larger than the trade-mark name. Certain countries have even gone so far as to abolish trade-marks within the public sector.
To avoid confusion, which could jeopardize the safety of patients, trade-marks cannot be derived from INN and, in particular, must not include their common stems. As already mentioned the selection of further names within a series will be seriously hindered by the use of a common stem in a brand-name.
Selection of INN
The names which are given the status of an INN are selected by the World Health Organization on the advice of experts from the WHO Expert Advisory Panel on the International Pharmacopoeia and Pharmaceutical Preparations. The process of INN selection follows three main steps:
- a request/application is made by the manufacturer or inventor; - after a review of the request a proposed INN is selected and published for comments; - after a time-period for objections has lapsed, the name will obtain the status of a recommended INN and will be published as such if no objection has been raised.
INN are selected in principle only for single, well-defined substances that can be unequivocally characterized by a chemical name (or formula). It is the policy of the INN programme not to select names for mixtures of substances, while substances that are not fully characterized are included in the INN system in exceptional cases only. INN are not selected for herbal substances (vegetable drugs) or for homoeopathic products. It is also the policy of the INN programme not to select names for those substances that have a long history of use for medical purposes under well-established names such as those of alkaloids (e.g. morphine, codeine), or trivial chemical names (e.g. acetic acid).
An INN is usually designated for the active part of the molecule only, to avoid the multiplication of entries in cases where several salts, esters, etc. are actually used. In such cases, the user of the INN has to create a modified INN (INNM) himself ; mepyramine maleate (a salt of mepyramine with maleic acid) is an example of an INNM. When the creation of an INNM would require the use of a long or inconvenient name for the radical part of the INNM, the INN programme will select a short name for such a radical (for example, mesilate for methanesulfonate).
In the process of INN selection, the rights of existing trade-mark owners are fully protected. If in the period of four months following the publication of a proposed INN, a formal objection is filed by an interested person who considers that the proposed INN is in conflict with an existing trade-mark, WHO will actively pursue an arrangement to obtain a withdrawal of such an objection or will reconsider the proposed name. As long as the objection exists, WHO will not publish it as a recommended INN.
The selection of a new INN relies on a strict procedure. Upon receipt of an INN request form, the WHO Secretariat examines the suggested names for conformity with the general rules, for similarities with published INN and potential conflicts with existing names, including published INN and trade-marks. A note summarizing the result of these checks is added and the request is subsequently forwarded to the INN experts for comments. Once all experts agree upon one name, the applicant is informed of the selected name.
Newly selected, proposed INN are then published in WHO Drug Information, which indicates a deadline for a 4-month objection period. This period is allowed for comments and/or objections to the published names to be raised. The reasons for any objection must be stated clearly and these will be evaluated by the experts for further action. Users are invited to refrain from using the proposed name until it becomes a recommended INN, in order to avoid confusion should the name be modified. Two lists of proposed INN are published yearly.
The final stage of the selection process is the recommended INN. Once a name has been published as a recommended INN it will not normally be modified further and is ready for use in labelling, publications, on drug information. It will serve to identify the active pharmaceutical substance during its life-time worldwide. Since the name is available in the public domain it may be used freely. However, it should not be registered as a trade-mark since this would prevent its use by other parties.
Recommended INN are published in the WHO Drug Information as a consequence of the objection procedure applied to proposed INN. As from 1997, two lists of proposed INN are published yearly and as from list 37 of recommended INN, graphic formulae are also included for better identification of the substances.
The procedure for selecting recommended INN is carried out in accordance with a text adopted by the WHO Executive Board.
Names for radicals and groups
Names for radicals and groups During the 1975 meeting on Nonproprietary Names for Pharmaceutical Substances the experts discussed the issue of INN for salts and esters and noted that requests had frequently been received for INN for salts, esters, or combination products of substances for which INN already existed. At that time, the experts decided that INN for the simple salt and esters should be devised from the INN in conformity with normal chemical practice.
Some of the radicals and groups involved are, however, of such complex composition that it makes it inconvenient to use the chemical nomenclature. It was thus decided that in such cases, shorter nonproprietary names are selected for these inactive moieties and published in proposed lists under the title "Names for Radicals and Groups". Separate names for salts and esters derived from this procedure are not published. If a "radical and group name" is used in conjunction with an INN, they are referred to as International Nonproprietary Name (Modified) or INNM.
A comprehensive list of radicals and groups may be obtained from WHO's Marketing and Dissemination unit (INNs: Names for radicals and groups, combined summary list).
Modified INN (INNM)
In principle, INN are selected only for the active part of the molecule which is usually the base, acid or alcohol. In some cases, however, the active molecules need to be expanded for various reasons, such as formulation purposes, bioavailability or absorption rate. In 1975 the experts designated for the selection of INN decided to adopt a new policy for naming such molecules. In future, names for different salts or esters of the same active substance should differ only with regard to the inactive moiety of the molecule. For example, oxacillin and ibufenac are INN and their salts are named oxacillin sodium and ibufenac sodium. The latter are called modified INN (INNM).
Before the existence of this rule, some INN were published for salts. In such cases, the term "modified INN" may also be used for a base or acid. For example, levothyroxine sodium was published as an INN and levothyroxine may thus be referred to as an INNM.
Protection of INN
Lists of both proposed and recommended INN are sent by WHO, together with a note verbale, to the Organization's Member States (at present 191), to national pharmacopoeia commissions and to other bodies designated by Member States. In his note verbale, the Director-General of the World Health Organization requests that Member States should take such steps as are necessary to prevent the acquisition of proprietary rights on the name, including prohibiting registration of the name as a trade name.
Over the years, the need to maintain the integrity of the INN system has become urgent. This is reflected in the following extract from the Fifth Report of the WHO Expert Committee on the Use of Essential Drugs which met in November 1991 :
"The procedure for selecting INNs allows manufacturers to contest names that are either identical or similar to their licensed trade-marks. In contrast, trade-mark applications are disallowed, in accordance with the present procedure, only when they are identical to an INN. A case for increased protection of INNs is now apparent as a result of competitive promotion of products no longer protected by patents. Rather than marketing these products under generic name, many companies apply for a trade-mark derived from an INN and, in particular, including the INN common stem. This practice endangers the principle that INNs are public property; it can frustrate the rational selection of further INNs for related substances, and it will ultimately compromise the safety of patients by promoting confusion in drug nomenclature."
These concerns were debated during the sixth International Conference of Drug Regulatory Authorities (ICDRA), in Ottawa, in October 1991. Based on recommendations made by the WHO Expert Committee on the use of Essential Drugs, the resolution WHA46.19 on Nonproprietary names for pharmaceutical substances was adopted by the Forty-sixth World Health Assembly in 1993, requesting Member States to:
- "…enact rules or regulations, as necessary, to ensure that international nonproprietary names (or the equivalent nationally approved generic names) used in the labelling and advertising of pharmaceutical products are always displayed prominently; - …encourage manufacturers to rely on their corporate name and the international nonproprietary names, rather than on trade-marks, to promote and market multisource products introduced after the expiry of a patent; - …develop policy guidelines on the use and protection of international nonproprietary names, and to discourage the use of names derived from them, and particularly names including established stems, as trade-marks."
In the note verbale, attention is drawn to this resolution concerning the use and protection of INN.
As a matter of principle, it may thus be recommended that trade-marks should not be derived from INN. In particular, the intentional incorporation of meaningful INN stems in trade-marks should be avoided.
Similarly, inclusion of elements from biochemical nomenclature (like ?feron from interferon, or ?leukin from interleukin) in trade marks in anticipation is discouraged since these elements are likely to be utilized as stems within the INN nomenclature. Their inclusion in trade-marks could pre-empt the logical development of the INN nomenclature.
In accordance with resolution WHA46.19, registration of an INN together with a firm's name is perfectly acceptable, as long as it does not prevent another manufacturer from using the same approach.
Guidelines on the Use of INNs for Pharmaceutical Substances (1997)