ESSR’14 17th European Symposium on.PDF

ESSR’14: 17th European Symposium on Radiopharmacy and Radiopharmaceuticals Pamplona, 25 April 2014 Preclinical safety testing of diagnostic and therapeutic radiopharmaceuticals - regulatory requirements Rex FitzGerald SCAHT / Universität Basel Klingelbergstrasse 61 4056 Basel Contents of talk • General preclinical safety testing requirements (ICH) • US and EU radiopharmaceutical regulations • ICH microdose approach • Swissmedic summary recommendations ESSR’14 / Radiopharmaceutical preclinical safety / Rex FitzGerald / 25-Apr-2014 2 Drug safety testing Is the molecule too toxic to Is it likely to be safe in patients? develop? At what dose? Any unexpected toxicity Is drug still safe in real-life in clinical trials? clinical practice? ESSR’14 / Radiopharmaceutical preclinical safety / Rex FitzGerald / 25-Apr-2014 3 Early drug development Safety questions: • Is the candidate mutagenic or cytotoxic in vitro? • What are the probable toxicity target organs? • Are drug metabolism and pharmacokinetics (DMPK) adequately characterized (target exposure, toxic metabolites) ESSR’14 / Radiopharmaceutical preclinical safety / Rex FitzGerald / 25-Apr-2014 4 Early drug development In silico: Activity / toxicity related to In vitro: chemical structure Subcellular systems, cell physico-chemical properties lines primary cells In vivo: Short-term animal studies, conventional endpoints, DMPK ESSR’14 / Radiopharmaceutical pre