WHO Technical Report Series 948 SPECIFICATIONS FOR PHARMACEUTICAL PREPARATIONS SPECIFICATIONS The Expert Committee on Specifi cations for Pharmaceutical WHO EXPERT COMMITTEE Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. ON SPECIFICATIONS FOR Standards are developed by the Committee through worldwide consultation and an international consensus-building process. PHARMACEUTICAL PREPARATIONS The following new standards and guidelines were adopted and recommended for use: the current list of available International Chemical Reference Substances and International Infrared Reference Spectra; guidelines on the active pharmaceutical ingredient master fi le procedure; the procedure for assessing the acceptability of male latex condoms and that of intrauterine devices for purchase by United Nations and other agencies; and a review of International Nonproprietary Names for biological and biotechnological substances. Forty-second report WHO Technical Report Series — 948 WHO Technical ISBN 9789241209489 The World Health Organization was established in 1948 as a specialized agency of the United Nations serving as the directing and coordinating authority for SELECTED WHO PUBLICATIONS OF RELATED INTEREST international health matters and public health. One of WHO’s constitutional functions is to provide objective and reliable information and advice in the The International Pharmacopoeia, fourth edition. fi eld of human health, a responsibility that it fulfi ls in part through its extensive Volume 1: general notices; monographs for pharmaceutical substances (A–O) programme of publications. The Organization seeks through its publications to Volume 2: monographs for pharmaceutical substances (P–Z); monographs for dosage forms support national health strategies and address the most pressing public health and radiopharmaceutical preparations; methods of analysis; reagents. concerns of populations around the world. To respond to the needs of Member 2006 (1500 pages), also available in CD-ROM format and on line States at all levels of development, WHO publishes practical manuals, handbooks First supplement: general notices; monographs for pharmaceutical substances; monographs and training material for specifi c categories of health workers; internationally for dosage forms; general and specifi c monographs; methods of analysis; International applicable guidelines and standards; reviews and analyses of health policies, Chemical Reference Substances; International Infrared Reference Spectra; reagents, test programmes and research; and state-of-the-art consensus reports that offer solutions and volumetric solutions, 2008 (in press) technical advice and recommendations for decision-makers. These books are closely tied to the Organization’s priority activities, encompassing disease Basic tests for drugs: pharmaceutical substances, prevention and control, the development of equitable health systems based medicinal plant materials and dosage forms on primary health care, and health promotion for individuals and communities. 1998 (94 pages) Progress towards better health for all also demands the global dissemination and exchange of information that draws on the knowledge and experience of Basic tests for pharmaceutical dosage forms all WHO’s Member countries and the collaboration of world leaders in public 1991 (134 pages) health and the biomedical sciences. To ensure the widest possible availability of authoritative information and guidance on health matters, WHO secures Quality Assurance of Pharmaceuticals: a compendium of guidelines and related materials the broad international distribution of its publications and encourages their Volume 1: 1997 (244 pages) translation and adaptation. By helping to promote and protect health and Volume 2: Good manufacturing practices and inspection. prevent and control disease throughout the world, WHO’s books contribute to 2nd updated edition, 2007 (in press) achieving the Organization’s principal objective — the attainment by all people Also available on: WHO training modules on GMP. A resource and study pack for trainers, of the highest possible level of health. 2007 (CD-ROM) WHO Expert Committee on Specifi cations for Pharmaceutical Preparations Forty-fi rst report. The WHO Technical Report Series makes available the fi ndings of various WHO Technical Report Series, No. 943, 2007 (156 pages) international groups of experts that provide WHO with the latest scientifi c and technical advice on a broad range of medical and public health subjects. International Nonproprietary Names (INN) for pharmaceutical substances Members of such expert groups serve without remuneration in their personal Cumulative List no. 12 capacities rather than as representatives of governments or other bodies; their 2007 (available in CD-ROM format only) views do not necessarily refl ect the decisions or the stated policy of WHO. An annual subscription to this series, comprising about six such reports, costs The use of essential medicines CHF 168.00/US$ 151.00 (CHF 128.40/US$ 115.00 in developing countries). Report of the WHO Expert Committee (including the 15th Model List of Essential Medicines). For further information, please contact: WHO Press, World Health Organization, WHO Technical Report Series, No. 946, 2007 (163 pages). First WHO Model List of 20 avenue Appia, 1211 Geneva 27, Switzerland (tel. +41 22 791 3264; Essential Medicines for Children (http://www.who.int/childmedicines/en/index.html) fax: +41 22 791 4857; e-mail: [email protected]; order on line: http://www. who.int/bookorders). WHO Expert Committee on Biological Standardization Fifty-fi fth report. WHO Technical Report Series, No. 941, 2008 (290 pages) (in press) Further information on these and other WHO publications can be obtained from WHO Press, World Health Organization, 1211 Geneva 27, Switzerland. This report contains the collective views of an international group of experts, and does not necessarily represent the decisions or the stated policy of the World Health Organization WHO Technical Report Series 948 WHO EXPERT COMMITTEE ON SPECIFICATIONS FOR PHARMACEUTICAL PREPARATIONS Forty-second report Geneva 2007 WHO Library Cataloguing-in-Publication DataPublications of the World Health Organization enjoy copyright protection in accordance with the WHO Library Cataloguing-in-Publication Data Forty-second report of the WHO Expert Committee on Specifi cations for Pharmaceutical Preparations. (WHO Technical Report Series, No. 948) 1. Pharmaceutical preparations - standards. 2. Technology, Pharmaceuticals - standards. 3. Drug industry - legislation. 4. Quality control. I. World Health Organization. II. Series. ISBN 978 92 4 120948 9 (NLM classifi cation: QV 771) ISSN 0512-3054 © World Health Organization 2008 All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: [email protected]). Requests for permission to reproduce or translate WHO publications — whether for sale or for noncommercial distribution — should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; e-mail: [email protected]). The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specifi c companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. This publication contains the collective views of an international group of experts and does not necessarily represent the decisions or the stated policy of the World Health Organization. Typeset in Switzerland Printed in Switzerland Contents 1. Introduction 1 2. General policy 8 2.1 Collaboration with international organizations and agencies 8 2.2 Cross-cutting pharmaceuticals — quality assurance issues 13 2.3 Essential medicines for children 17 2.4 Counterfeit medicines 18 3. Quality control — specifi cations and tests 18 3.1 The International Pharmacopoeia (4th edition) 18 3.2 Proposed new work plan 18 3.3 Specifi cations for medicines, including children’s medicines 19 3.4 Revision of texts 21 3.5 General monographs for dosage forms and associated method texts 21 3.6 Radiopharmaceuticals 25 3.7 Dissolution tests for addition to specifi c monographs 26 4. Quality control — International Chemical Reference Substances and International Infrared Reference Spectra 28 4.1 Annual report of the WHO Collaborating Centre 28 4.2 Adoption of new International Chemical