Labelling Requirements for Investigational Medicinal Products in Multinational Clinical Trials: Bureaucratic Cost Driver or Added Value? Wissenschaftliche Prüfungsarbeit zur Erlangung des Titels „Master of Drug Regulatory Affairs“ der Mathematisch-Naturwissenschaftlichen Fakultät der Rheinischen Friedrich-Wilhelms-Universität Bonn vorgelegt von Dr. Astrid Weyermann aus Herford Bonn 2006 Dr. Astrid Weyermann Labelling requirements for IMPs in multinational CTs Betreuer und 1. Referent: H. Jopp Zweiter Referent: Dr. J. Hofer Page 2 / 71 Dr. Astrid Weyermann Labelling requirements for IMPs in multinational CTs TABLE OF CONTENTS TABLE OF CONTENTS .......................................................................................................................... 3 1 EXECUTIVE SUMMARY.................................................................................................................. 6 2 INTRODUCTION.............................................................................................................................. 7 2.1 Definitions ..................................................................................................................................... 7 2.2 Clinical Trials ................................................................................................................................ 8 2.2.1 Types of clinical trials ............................................................................................................ 8 2.2.1.1 Phases of Clinical Trials .................................................................................................... 8 2.2.1.2 Design of Clinical Trials ..................................................................................................... 9 2.2.2 Medicinal products in clinical trials ...................................................................................... 10 2.2.3 Activities during preparation of a clinical trial ...................................................................... 11 2.3 Legal Framework of Clinical Trials ............................................................................................. 11 2.3.1 Regulatory Background in Europe ...................................................................................... 12 2.3.1.1 Good Clinical Practice ..................................................................................................... 12 2.3.1.2 Good Manufacturing Practice .......................................................................................... 13 2.3.2 Requirements in non-EU Member States............................................................................ 14 2.3.2.1 Switzerland ...................................................................................................................... 14 2.3.2.2 Japan ............................................................................................................................... 14 2.3.2.3 United States of America ................................................................................................. 14 3 REGULATORY COMPLIANCE: LABELLING REQUIREMENTS.................................................. 15 3.1 Information related to the Clinical Trial.......................................................................................16 3.1.1 Name, address and telephone number of sponsor, contract research organisation or investigator .......................................................................................................................... 16 3.1.2 Trial reference code............................................................................................................. 17 3.1.3 Trial subject identification number or treatment number ..................................................... 17 3.1.4 Name of the investigator...................................................................................................... 18 3.1.5 Directions for use................................................................................................................. 18 3.1.6 “For clinical trial use only”.................................................................................................... 18 3.2 Information related to the Investigational Medicinal Product...................................................... 19 3.2.1 Pharmaceutical dosage form, route of administration, quantity of dosage units................. 19 3.2.2 Batch and/or code number .................................................................................................. 20 3.2.3 Storage conditions............................................................................................................... 20 3.2.4 Period of use........................................................................................................................ 20 3.2.5 “Keep out of reach of children” ............................................................................................ 21 3.3 Deviating requirements for approved investigational medicinal products .................................. 21 3.4 Implementation of the EU-labelling requirements ...................................................................... 22 3.4.1 Austria.................................................................................................................................. 22 3.4.2 Belgium................................................................................................................................ 22 3.4.3 Czech Republic ................................................................................................................... 23 3.4.4 France.................................................................................................................................. 23 3.4.5 Germany.............................................................................................................................. 23 3.4.6 Italy ...................................................................................................................................... 24 3.4.7 The Netherlands .................................................................................................................. 24 3.4.8 Spain.................................................................................................................................... 24 3.4.9 Sweden................................................................................................................................ 25 3.4.10 United Kingdom ................................................................................................................... 25 Page 3 / 71 Dr. Astrid Weyermann Labelling requirements for IMPs in multinational CTs 3.5 Requirements in non-EU Member States................................................................................... 25 3.5.1 Switzerland .......................................................................................................................... 25 3.5.2 Japan................................................................................................................................... 26 3.5.3 United States ....................................................................................................................... 26 3.6 Summary of labelling requirements ............................................................................................ 27 3.6.1 Essential requirements for the labelling .............................................................................. 27 3.6.2 Further requirements for the labelling ................................................................................. 28 4 DECISION PROCESS FOR THE LABELLING – FLOW CHART.................................................. 29 5 DECISION PROCESS FOR THE LABELLING.............................................................................. 34 5.1 Decision statement for the team.................................................................................................34 5.2 Objectives for the labelling ......................................................................................................... 34 5.2.1 Regulatory Compliance of labelling information.................................................................. 34 5.2.2 Optimisation of timing ..........................................................................................................35 5.2.3 Consideration of costs ......................................................................................................... 35 5.2.4 Facilitation of manufacturing of the investigational medicinal product ................................ 35 5.2.5 Facilitation of clinical trial logistics....................................................................................... 36 5.2.6 Summary of Criteria.............................................................................................................36 5.3 Alternatives ................................................................................................................................. 37 5.3.1 Number of different labels ................................................................................................... 37 5.3.1.1 One label for all countries ................................................................................................ 37 5.3.1.2 One label for each country............................................................................................... 37 5.3.1.3 Some labels