DDTEC-295; No of Pages 7 Please cite this article in press as: Decristoforo, C. and Schwarz, S.W. Radiopharmacy: regulations and legislations in relation to human applications, Drug Discov Today: Technol (2011), doi:10.1016/j.ddtec.2011.11.012 TECHNOLOGIES DRUGDISCOVERY TODAY Radiopharmacy: regulations and legislations in relation to human applications Clemens Decristoforo 1, * , Sally W. Schwarz 2 1 Department of Nuclear Medicine, Innsbruck Medical University, Innsbruck, Austria 2 Department of Radiology, Division of Radiological Sciences, Washington University School of Medicine, St. Louis, MO, USA Radiopharmaceuticals (RPs) have attracted tremen- dous interest as molecular imaging tracers in diagnos- tic applications and as biomarkers in drug development, in particular using Positron Emission Tomography (PET). This article summarizes impor- tant legal documents and guidelines in relation to human application of PET-RPs that pose a major chal- lenge in implementing the full potential of this tech- nology, thereby differentiating the US from the European situation. Regulations are reviewed with respect to licensing, conducting clinical trials and RP production – including Good Manufacturing Practice (GMP) for radioactive compounds. Professional requirements, including education, are discussed, with an outlook on future developments. Section editors: Nicolau Beckmann – Novartis Institutes for BioMedical Research, Basel, Switzerland. Bert Windhorst – VU Medical Center, Amsterdam, The Netherlands. Introduction Radiopharmaceuticals (RPs) have attracted tremendous inter- est especially for diagnostic applications and as biomarkers for use in drug development over the past 5 years [1]. In particular, molecular imaging using Positron Emission Tomography (PET), with its improved resolution and unequaled sensitivity, has led to worldwide establishment of PET facilities both at academic and clinical centers [2]. PET-RPs typically incorpo- rate short-lived radionuclides usually ranging from 2 to 110 min and have low mass levels, usually mg quantities or less. Even though a wide variety of PET-RPs, including 18 F-FDG, have been developed and have shown diagnostic potential in large patient populations [3], the regulatory framework for human applications has been a major hurdle in allowing a more widespread use of this technology. This article will try to summarize these regulations and guidelines, focusing on one major issue, the use of new RPs, without a marketing author- ization (MA). It covers licensing, clinical trials, standards of preparation and professional requirements, including educa- tion and training, and will take into consideration the differ- ences in regulatory environments in the US and Europe. Major abbreviations of importance in relation to these topics are summarized in Table 1. European background In Europe most PET RPs were developed in independent research groups or university hospitals, that is academic cen- ters without commercial distribution. New RPs were rapidly implemented in clinical practice in many countries based on exemptions from the need for an MA as stated in Directive 2001/83 [4], Title II, ‘Scope’, Article 2 + 3, allowing the ‘extem- poraneous’ preparation of medicinal products (in this case RPs) based on a medical prescription for an individual patient Drug Discovery Today: Technologies Vol. xxx, No. xx 2011 Editors-in-Chief Kelvin Lam – Harvard University, USA Henk Timmerman – Vrije Universiteit, The Netherlands Imaging techniques *Corresponding author.: C. Decristoforo (Clemens.Decristoforo@uki.at) 1740-6749/$ ß 2011 Published by Elsevier Ltd. DOI: 10.1016/j.ddtec.2011.11.012 e1