History

The history of The International Pharmacopoeia dates back to 1874 when the need to standardize terminology and to specify dosages and composition of drugs led to attempts to produce an international pharmacopoeial compendium. The first conference, called by the Belgian Government and held in Brussels in 1902, resulted in the Agreement for the Unification of the Formulae of Potent Drugs, which was ratified in 1906 by 19 countries. The outcome considerably influenced the subsequent publication of national pharmacopoeias.

A second agreement, the Brussels Agreement, was drawn up in 1925 and ratified in 1929. This 41-article agreement stipulated that the League of Nations would be responsible for the administrative work to produce a unified pharmacopoeia, and a permanent secretariat of an international organization would coordinate the work of national pharmacopoeial commissions. General principles for the preparation of galenicals, maximal doses, nomenclature and biological testing of arsenobenzones were included in the articles of this agreement, as was a table of dosage strengths and descriptions for 77 drug substances and preparations.

In response to repeated calls from pharmaceutical experts in various countries that the Brussels Agreement be revised and extended to cover an international pharmacopoeia, the Health Organization of the League of Nations set up a Technical Commission of Pharmacopoeial Experts in 1937. This first committee comprised seven experts from Belgium, Denmark, France, Netherlands, Switzerland, the United Kingdom (Chairman), and the United States of America.

In 1947 the Interim Commission of the World Health Organization (WHO) took over the work on pharmacopoeias previously undertaken by the Health Organization of the League of Nations, and set up an Expert Committee on the Unification of Pharmacopoeias to continue the work of the League's Technical Commission. The aim of the Expert Committee was to produce a draft international agreement for the unification of pharmacopoeias, modifying and extending the existing Agreement for the Unification of the Formulae of Potent Drugs.

In 1948 the First World Health Assembly approved the establishment of the Expert Committee by the Interim Commission. In 1951 this became the Expert Committee on the International Pharmacopoeia; and subsequently, in 1959, the Expert Committee on Specifications for Pharmaceutical Preparations. The panel has always been named the WHO Expert Advisory Panel on the International Pharmacopoeia and Pharmaceutical Preparations.

Article 2 of the WHO Constitution states that one of the functions of the Organization is "to develop, establish and promote international standards with respect to food, biological, pharmaceutical and similar products". The International Pharmacopoeia falls clearly into this category. In this context also the Third World Health Assembly in 1950 adopted a resolution to create the International Nonproprietary Names (INN) Programme in order to identify pharmaceutical substances unambiguously on a worldwide basis and to provide a single nonproprietary name to be used in monographs.

First edition

The Third World Health Assembly, held in May 1950, formally approved the publication of the Pharmacopoea Internationalis and recommended, in accordance with Article 23 of the WHO Constitution, "the eventual inclusion of its provisions by the authorities responsible for the pharmacopoeias". It was thus recommended that the Pharmacopoea Internationalis was not intended to be a legal pharmacopoeia in any country unless adopted by the pharmacopoeial authority of that country. From that moment WHO constituted the Permanent International Pharmacopoeia Secretariat.

The first edition, published with the aim of creating a worldwide, unified pharmacopoeia, relied on collaboration with national pharmacopoeia commissions for its preparation. It was published in two volumes (1951 and 1955) and a supplement (1959) in English, French and Spanish, and was also translated into German and Japanese. Altogether, it included 344 monographs on drug substances, 183 monographs on dosage forms (capsules, injections, tablets and tinctures) and 84 tests, methods and general requirements.

A large number of national pharmacopoeias and official lists were examined and assistance was also obtained from the International Pharmaceutical Federation (FIP) to determine the selection of substances and products to be described in the pharmacopoeia. Latin was chosen for the monograph titles because of its distinction as an international language. Experts collaborated with the WHO Expert Committee on Biological Standardization with regard to biological products and with those working in specific divisions, e.g. malaria, maternal and child health, mental health and venereal diseases, to help collate the required information.

Second edition

The second edition was published in 1967 as Specifications for the Quality Control of Pharmaceutical Preparations, with a subtitle classifying it as the second edition of The International Pharmacopoeia.

Owing to the development of new analytical techniques such as infrared spectroscopy, chromatography (column, paper and thin-layer), non-aqueous titration and radioactivity, the second edition incorporated numerous alterations and constituted a revision of the first edition.

The selection of monographs and appendices was based largely on the availability, at the time of preparation, of specifications intended for publication in national pharmacopoeias and in other volumes of specifications for pharmaceutical quality control. Specifications for 162 pharmaceutical preparations not included in the first edition were introduced in the second edition, while 114 monographs were deleted, based on feedback from the first edition. New analytical methods were also added. The specifications and methods in the monographs were tested in a number of national pharmacopoeial and pharmaceutical quality control laboratories, in pharmaceutical manufacturers' laboratories and at various pharmacopoeial institutes.

Special thanks were expressed to the authorities of the British Pharmacopoeia and the United States Pharmacopeia.

Third edition

In 1975 the purpose of The International Pharmacopoeia was reconsidered. It was decided that the publication should focus more on the needs of developing countries and recommend only simple, classical chemical techniques that had been shown to be sound. Priority would be given to drugs that were widely used throughout the world, with emphasis on the therapeutic value of these drugs. High priority would be accorded to drugs important to WHO health programmes, and to those likely to contain impurities arising from degradation or due to difficulties in their manufacture. Wherever possible, classical procedures would be used in the analytical methods so that the pharmacopoeia could be applied without the need for expensive equipment. Where a sophisticated analytical method was suggested an alternative, less complex method would also be proposed.

Since 1979 the drugs appearing in The International Pharmacopoeia have been selected from the list of essential drugs based on the first report of the WHO Expert Committee on the Selection of Essential Drugs. Specifications are provided in the monographs for the identification, purity and content of the essential drugs appearing in the WHO Model List of Essential Drugs and their updates.

The third edition eventually consisted of five volumes: Volume 1 contained general methods of analysis; Volumes 2 and 3, quality specifications for the majority of essential drug substances in the WHO Model List of Essential Drugs; and Volume 4, information on tests, methods and general requirements and quality specifications for pharmaceutical substances, excipients and dosage forms. Volume 5 contained tests and general requirements for dosage forms and quality specifications for pharmaceutical substances and tablets, which practically completed the list of monographs for active pharmaceutical substances, and a section on antimalarial drug substances and their most widely used dosage forms.

Fourth edition

Volumes 1 and 2 of the fourth edition were published together in 2006. Volume 1 contains the General Notices and many of the monographs for pharmaceutical substances and Volume 2 contains the remaining monographs for pharmaceutical substances together with those for dosage forms and radiopharmaceutical preparations, the methods of analysis and the reagents section and index. The main volumes of this edition consolidated and updated the texts of the five separate volumes of the third edition and included new monographs for antiretroviral substances.

The first supplement, published in 2008, contained new and revised monographs for pharmaceutical substances and dosage forms together with additions and amendments to the texts published in Volumes 1 and 2. As with the main volumes, the first supplement was published simultaneously in print, as a CD-ROM and online. The replacement CD-ROM contained the complete text of the fourth edition comprising Volumes 1 and 2 as amended and augmented by the text of the first supplement.

The new monographs published in the first supplement included additional antiretroviral substances, antiretroviral dosage forms and antituberculosis dosage forms including 2-, 3-, and 4-component fixed-dose preparations.

Similarly as for the first supplement, the second supplement, published in 2011, contains new and revised monographs for pharmaceutical substances and dosage forms together with additions and amendments to the texts already published in the fourth edition.

The second supplement is published in two electronic formats – as a CD-ROM and online. The replacement CD-ROM is, therefore, a cumulative version of the current fourth edition, comprising Volumes 1, Volume 2 and the first supplement as amended and augmented by the text of the second supplement.

With the publication of this second supplement, the fourth edition sees its collection of monographs expanded for both active substances and dosage forms, notably for antiretroviral, antimalarial, antituberculosis and anti-infectives medicines, including specifications for paediatric preparations as recommended in the WHO Model Lists of Essential Medicines. In collaboration with the International Atomic Energy Agency (IAEA), the texts devoted to Radiopharmaceuticals have also been revised and replaced by a comprehensive section which is now composed of general texts and a great number of specific monographs for radiopharmaceutical preparations.

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