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Draft General International Pharmacopoeia Monograph for Radiopharmaceuticals Revision (September 2007)

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Draft General International Pharmacopoeia Monograph for Radiopharmaceuticals Revision (September 2007) Working document QAS/07.242 September 2007 RESTRICTED Draft general International Pharmacopoeia monograph for Radiopharmaceuticals Revision (September 2007) DRAFT FOR COMMENT Please send any comments on the revision of this draft general monograph for Radiopharmaceuticals to Dr S. Kopp with a copy to Ms M.-L. Rabouhans, Quality Assurance and Safety: Medicines, Medicines Policy and Standards, World Health Organization, 1211 Geneva 27, Switzerland; fax: (+41 22) 791 4730 or e-mail: [email protected] and [email protected] by 10 November 2007. © World Health Organization 2007 All rights reserved. This draft is intended for a restricted audience only, i.e. the individuals and organizations having received this draft. The draft may not be reviewed, abstracted, quoted, reproduced, transmitted, distributed, translated or adapted, in part or in whole, in any form or by any means outside these individuals and organizations (including the organizations’ concerned staff and member organizations) without the permission of WHO. The draft should not be displayed on any website. Please send any request for permission to: Dr Sabine Kopp, Quality Assurance & Safety: Medicines (QSM), Department of Medicines Policy and Standards (PSM), World Health Organization, CH-1211 Geneva 27, Switzerland. Fax: (41-22) 791 4730; e-mail: [email protected]. The designations employed and the presentation of the material in this draft 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 specific 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. The World Health Organization does not warrant that the information contained in this draft is complete and correct and shall not be liable for any damages incurred as a result of its use. Working document QAS/07.242 page 2 SCHEDULE FOR THE ADOPTION PROCESS OF DOCUMENT QAS/07.242 Draft general International Pharmacopoeia monograph for Radiopharmaceuticals Revision Date Draft revision of general monograph September-October 2007 mailed out for comments Collation of any comments received October 2007 Presentation to WHO Expert Committee on October 2007 Specifications for Pharmaceutical Preparations Further follow-up action as required October 2007 - … Working document QAS/07.242 page 3 RADIOPHARMACEUTICALS Introduction The World Health Organization and the International Atomic Energy Agency (IAEA) have been working jointly on specifications for Radiopharmaceuticals. Following consultation and discussion, it was agreed that this work should include inter alia revision of the general monograph in The International Pharmacopoeia and the preparation of monographs for individual radiopharmaceuticals. Meanwhile, for the main volumes of the Fourth edition of The International Pharmacopoeia, published in December 2006, the section on Monographs for Radiopharmaceuticals consists of the general monograph for Radiopharmaceuticals as included in the 3rd edition. A draft revised general monograph for Radiopharmaceuticals has now been prepared by the IAEA together with a first set of individual draft monographs for about 30 radiopharmaceutical preparations (more drafts are in preparation) for addition to the 4th edition of The International Pharmacopoeia. These texts are now being circulated by WHO for comment in line with the usual consultative process for monograph development. As noted within the documents however, the WHO Secretariat has not, as yet, adapted these texts to the format and style of The International Pharmacopoeia. This will be carried out at a later stage. Comments are therefore invited on the technical content of the draft monograph texts. In addition to publishing these monographs in the section on Radiopharmaceuticals in a future Supplement to The International Pharmacopoeia, it is intended that they also form part of a joint IAEA/WHO publication that would also include other texts relevant to the manufacture and use of radiopharmaceuticals. In including the monographs in such a "stand-alone" publication, it would be necessary to supplement them with relevant supporting texts from The International Pharmacopoeia. These would include, for example, the General Notices, the general monographs for Parenteral Preparations and Capsules, selected Methods of Analysis (such as 1.13 Determination of pH, 1.14.4 High performance liquid chromatography, 3.4 Test for bacterial endotoxins). Working document QAS/07.242 page 4 Draft general monograph for: Radiopharmaceuticals [Note from the Secretariat: Before inclusion in The International Pharmacopoeia this draft general monograph will be adapted to the usual pharmacopoeial format, layout and editorial style. An updated table of the physical characteristics of radionuclides will be included.] This general monograph is intended to be read in conjunction with the individual monographs on radiopharmaceutical preparations. A radiopharmaceutical preparation that is subject of an individual monograph in The International Pharmacopoeia complies with the general requirements stated below. Radiopharmaceuticals are unique medicinal formulations containing radioisotope which are used in major clinical areas such as oncology, myocardial perfusion and infections. The facilities and procedures for the production, use, and storage of radiopharmaceuticals are generally subject to licensing by national and/or regional authorities. This licensing will generally include regulations for the pharmaceutical preparations and for the radioactive materials. Additional regulations may apply for issues such as transportation or dispensing of radiopharmaceuticals. Each producer or user must be thoroughly cognizant of the national requirements pertaining to the articles concerned. GMP guidelines are available in Quality assurance of pharmaceuticals, Volume 2: Good manufacturing practices and inspection (WHO, Geneva, 2004). In addition refer to IAEA publications on safe handling and production of radioisotopes. Radiopharmaceuticals are radioactive and can pose a risk to the personnel who prepare and administer them and the patients to whom they are administered. Specialized techniques are required to minimize the risks to personnel. All personnel involved in any part of the operation are required to have appropriate additional training specific. The maintenance personnel and support staff such as the cleaner should receive specific instruction and appropriate supervision whilst in the operational areas. Risk to patient should be minimised. It is essential to ensure that reproducible and clinically reliable results will be obtained. All operations should be carried out or supervised by personnel who have received expert training in handling radioactive materials. Definition Radiopharmaceuticals can be divided into four categories: Radiopharmaceutical preparation A radiopharmaceutical preparation is a medicinal product in a ready to use form suitable for human use which contains a radionuclide. The radionuclide is integral to the medicinal application of the preparation, making it appropriate for one or more diagnostic or therapeutic applications. Working document QAS/07.242 page 5 Radionuclide generator A system in which a daughter radionuclide (short half-life) is eluted (separated) from parent radionuclide/s (long half-life) and later used for preparation of radiopharmaceutical for medicinal purpose. Radiopharmaceutical precursor Any radionuclide produced for the radiolabelling process with a resultant product aimed for medicinal use. Kit for radiopharmaceutical preparation In general a vial containing essential pre- dispensed precursor/s, in general pre-sterilized, pre-validated products to which the appropriate radionuclide is added and diluted before medical use. In most cases this is a multidose vial which may require additional steps including boiling or filtration. The kits are designed for immediate use after preparation. See Annex for terminology applied to radiopharmaceuticals. Dosage form See The International Pharmacopoeia 4th edition (Ph. Int.) for more details on various dosage forms. In general radiopharmaceuticals are parenteral preparations however there are RP which are oral solutions or capsules and other forms. Therefore they should conform to the details outlined in these sections of the Ph. Int. Certain specific points related to RP are highlighted here. Parenteral RP solutions are sterile, pyrogen-free liquids solutions, or suspensions forms containing one or more radioisotope, packaged in a suitable container and stored in suitably shielded outer container. These are in either single-dose or multidose containers. It should be noted that although RP emit radiation they themselves are not self-sterilizing and, therefore, require the same consideration as normal parenteral preparation. Most RP are intended for ‘immediate use’. All the technetium based RP and positron emission tomography RP (PET) are prepared and used within 12 hours. This presents different set of challenges as it is not possible to comply with sterility
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