IAEA-TECDOC-1856 IAEA-TECDOC-1856 IAEA TECDOC SERIES Quality Control in the Production of Radiopharmaceuticals Quality Control in the Production of Radiopharmaceuticals IAEA-TECDOC-1856 Quality Control in the Production of Radiopharmaceuticals International Atomic Energy Agency Vienna ISBN 978–92–0–107918–3 ISSN 1011–4289 @ QUALITY CONTROL IN THE PRODUCTION OF RADIOPHARMACEUTICALS The following States are Members of the International Atomic Energy Agency: AFGHANISTAN GERMANY PALAU ALBANIA GHANA PANAMA ALGERIA GREECE PAPUA NEW GUINEA ANGOLA GRENADA PARAGUAY ANTIGUA AND BARBUDA GUATEMALA PERU ARGENTINA GUYANA PHILIPPINES ARMENIA HAITI POLAND AUSTRALIA HOLY SEE PORTUGAL AUSTRIA HONDURAS QATAR AZERBAIJAN HUNGARY REPUBLIC OF MOLDOVA BAHAMAS ICELAND ROMANIA BAHRAIN INDIA BANGLADESH INDONESIA RUSSIAN FEDERATION BARBADOS IRAN, ISLAMIC REPUBLIC OF RWANDA BELARUS IRAQ SAINT VINCENT AND BELGIUM IRELAND THE GRENADINES BELIZE ISRAEL SAN MARINO BENIN ITALY SAUDI ARABIA BOLIVIA, PLURINATIONAL JAMAICA SENEGAL STATE OF JAPAN SERBIA BOSNIA AND HERZEGOVINA JORDAN SEYCHELLES BOTSWANA KAZAKHSTAN SIERRA LEONE BRAZIL KENYA SINGAPORE BRUNEI DARUSSALAM KOREA, REPUBLIC OF SLOVAKIA BULGARIA KUWAIT SLOVENIA BURKINA FASO KYRGYZSTAN SOUTH AFRICA BURUNDI LAO PEOPLE’S DEMOCRATIC SPAIN CAMBODIA REPUBLIC SRI LANKA CAMEROON LATVIA SUDAN CANADA LEBANON SWEDEN CENTRAL AFRICAN LESOTHO SWITZERLAND REPUBLIC LIBERIA CHAD LIBYA SYRIAN ARAB REPUBLIC CHILE LIECHTENSTEIN TAJIKISTAN CHINA LITHUANIA THAILAND COLOMBIA LUXEMBOURG THE FORMER YUGOSLAV CONGO MADAGASCAR REPUBLIC OF MACEDONIA COSTA RICA MALAWI TOGO CÔTE D’IVOIRE MALAYSIA TRINIDAD AND TOBAGO CROATIA MALI TUNISIA CUBA MALTA TURKEY CYPRUS MARSHALL ISLANDS TURKMENISTAN CZECH REPUBLIC MAURITANIA UGANDA DEMOCRATIC REPUBLIC MAURITIUS UKRAINE OF THE CONGO MEXICO UNITED ARAB EMIRATES DENMARK MONACO UNITED KINGDOM OF DJIBOUTI MONGOLIA GREAT BRITAIN AND DOMINICA MONTENEGRO NORTHERN IRELAND DOMINICAN REPUBLIC MOROCCO UNITED REPUBLIC ECUADOR MOZAMBIQUE OF TANZANIA EGYPT MYANMAR UNITED STATES OF AMERICA EL SALVADOR NAMIBIA ERITREA NEPAL URUGUAY ESTONIA NETHERLANDS UZBEKISTAN ESWATINI NEW ZEALAND VANUATU ETHIOPIA NICARAGUA VENEZUELA, BOLIVARIAN FIJI NIGER REPUBLIC OF FINLAND NIGERIA VIET NAM FRANCE NORWAY YEMEN GABON OMAN ZAMBIA GEORGIA PAKISTAN ZIMBABWE The Agency’s Statute was approved on 23 October 1956 by the Conference on the Statute of the IAEA held at United Nations Headquarters, New York; it entered into force on 29 July 1957. The Headquarters of the Agency are situated in Vienna. Its principal objective is “to accelerate and enlarge the contribution of atomic energy to peace, health and prosperity throughout the world’’. IAEA-TECDOC-1856 QUALITY CONTROL IN THE PRODUCTION OF RADIOPHARMACEUTICALS INTERNATIONAL ATOMIC ENERGY AGENCY VIENNA, 2018 COPYRIGHT NOTICE All IAEA scientific and technical publications are protected by the terms of the Universal Copyright Convention as adopted in 1952 (Berne) and as revised in 1972 (Paris). The copyright has since been extended by the World Intellectual Property Organization (Geneva) to include electronic and virtual intellectual property. Permission to use whole or parts of texts contained in IAEA publications in printed or electronic form must be obtained and is usually subject to royalty agreements. Proposals for non-commercial reproductions and translations are welcomed and considered on a case-by-case basis. Enquiries should be addressed to the IAEA Publishing Section at: Marketing and Sales Unit, Publishing Section International Atomic Energy Agency Vienna International Centre PO Box 100 1400 Vienna, Austria fax: +43 1 26007 22529 tel.: +43 1 2600 22417 email: [email protected] www.iaea.org/books For further information on this publication, please contact: Radioisotope Products and Radiation Technology Section International Atomic Energy Agency Vienna International Centre PO Box 100 1400 Vienna, Austria Email: [email protected] © IAEA, 2018 Printed by the IAEA in Austria October 2018 Emended February 2019 IAEA Library Cataloguing in Publication Data Names: International Atomic Energy Agency. Title: Quality control in the production of radiopharmaceuticals / International Atomic Energy Agency. Description: Vienna : International Atomic Energy Agency, 2018. | Series: IAEA TECDOC series, ISSN 1011–4289 ; no. 1856 | Includes bibliographical references. Identifiers: IAEAL 18-01195 | ISBN 978–92–0–107918–3 (paperback : alk. paper) Subjects: LCSH: Radiopharmaceuticals. | Pharmaceutical industry — Quality control. | Radioisotopes in pharmacology. FOREWORD Radiopharmaceuticals are central to nuclear medicine applications for the diagnosis and therapy of human diseases, especially cancers and cardiovascular diseases. In the past few decades, advances in the production and quality control of emerging radiopharmaceuticals have led to the production of new radiopharmaceuticals and the availability of new production routes and methods for existing agents. Various new diagnostic agents in the field (such as 68Ga radiopharmaceuticals and generators) as well as therapeutic agents (such as alpha emitters) have already been added to the clinician toolkit. However, the lack of generic and peer-reviewed quality control guidelines and recommendations for their application in human patients is a major concern. To address this need, and in response to requests from Member States and professional societies, the IAEA developed this publication on quality control in the production of radiopharmaceuticals. It is expected to be of use for all professionals involved in the production and quality control of radiopharmaceuticals worldwide. This publication is an outcome of the work of an international team of experts in the field between 2016 and 2018. The IAEA wishes to thank the experts for their contributions. Special thanks are due to J. Ballinger (United Kingdom) and F. Dollé (France) for compiling the material, and J.S. Vera Araujo (Bolivarian Republic of Venezuela) for her editorial support. The IAEA officer responsible for this publication was A.R. Jalilian of the Division of Physical and Chemical Sciences. EDITORIAL NOTE This publication has been prepared from the original material as submitted by the contributors and has not been edited by the editorial staff of the IAEA. The views expressed remain the responsibility of the contributors and do not necessarily represent the views of the IAEA or its Member States. Neither the IAEA nor its Member States assume any responsibility for consequences which may arise from the use of this publication. This publication does not address questions of responsibility, legal or otherwise, for acts or omissions on the part of any person. The use of particular designations of countries or territories does not imply any judgement by the publisher, the IAEA, as to the legal status of such countries or territories, of their authorities and institutions or of the delimitation of their boundaries. The mention of names of specific companies or products (whether or not indicated as registered) does not imply any intention to infringe proprietary rights, nor should it be construed as an endorsement or recommendation on the part of the IAEA. The authors are responsible for having obtained the necessary permission for the IAEA to reproduce, translate or use material from sources already protected by copyrights. The IAEA has no responsibility for the persistence or accuracy of URLs for external or third party Internet web sites referred to in this publication and does not guarantee that any content on such web sites is, or will remain, accurate or appropriate. TABLE OF CONTENTS 1. INTRODUCTION .............................................................................................................. 1 1.1. BACKGROUND ......................................................................................................... 1 1.2. OBJECTIVE ................................................................................................................ 1 1.3. SCOPE ......................................................................................................................... 2 1.4 STRUCTURE ................................................................................................................... 2 2. QUALITY CONTROLS OF STARTING MATERIALS ..................................................... 3 2.1. INCOMING NON-RADIOACTIVE STARTING MATERIALS .................................. 3 2.2. INCOMING RADIOACTIVE STARTING MATERIALS ............................................ 3 2.3. IN-HOUSE-PRODUCED RADIOACTIVE STARTING MATERIALS....................... 3 2.4. IN-HOUSE NON-RADIOACTIVE PRODUCED STARTING MATERIALS ............. 3 2.4.1. Identity and purity ..................................................................................................... 3 2.5. QUALITY CONTROL OF RADIONUCLIDES ............................................................ 4 3. QUALITY CONTROL OF RADIONUCLINES AND RADIOPHARMACEUTICALS .... 4 3.1. RADIONUCLIDIC IDENTITY DETERMINATION .................................................... 4 3.1.1 Half-life determination ............................................................................................... 4 3.1.2. Gamma spectrometry ................................................................................................ 5 3.1.3. Radionuclidic purity .................................................................................................. 5 3.1.4. Dose-calibrator measurements .................................................................................