Labelling Requirements for Investigational …

1 Labelling Requirements for Investigational medicinal Products in Multinational Clinical Trials: Bureaucratic Cost Driver or Added Value? Wissenschaftliche Pr fungsarbeit zur Erlangung des Titels Master of Drug Regulatory Affairs der Mathematisch-Naturwissenschaftlichen Fakult t der Rheinischen Friedrich-Wilhelms-Universit t Bonn vorgelegt von Dr. Astrid Weyermann aus Herford Bonn 2006 Dr. Astrid Weyermann Labelling Requirements for IMPs in multinational CTs Page 2 / 71 Betreuer und 1. Referent: H. Jopp Zweiter Referent: Dr. J. Hofer Dr. Astrid Weyermann Labelling Requirements for IMPs in multinational CTs Page 3 / 71 TABLE OF CONTENTS TABLE OF CONTENTS.

2 3 1 EXECUTIVE 6 2 INTRODUCTION .. 7 Definitions .. 7 Clinical Trials .. 8 Types of clinical trials .. 8 Phases of Clinical Trials .. 8 Design of Clinical Trials .. 9 medicinal products in clinical trials .. 10 Activities during preparation of a clinical trial .. 11 Legal Framework of Clinical Trials ..11 Regulatory Background in Europe .. 12 Good Clinical Practice .. 12 Good Manufacturing Practice .. 13 Requirements in non-EU Member 14 Switzerland .. 14 Japan .. 14 United States of America .. 14 3 REGULATORY COMPLIANCE: Labelling 15 Information related to the Clinical Trial.

3 16 Name, address and telephone number of sponsor, contract research organisation or investigator .. 16 Trial reference 17 Trial subject identification number or treatment number .. 17 Name of the 18 Directions for 18 For clinical trial use only .. 18 Information related to the Investigational medicinal 19 Pharmaceutical dosage form, route of administration, quantity of dosage 19 Batch and/or code number .. 20 Storage conditions .. 20 Period of 20 Keep out of reach of children .. 21 Deviating Requirements for approved Investigational medicinal products .. 21 Implementation of the EU- Labelling Requirements .

4 22 22 22 Czech Republic .. 23 23 Germany .. 23 Italy .. 24 The Netherlands .. 24 24 25 United Kingdom .. 25 Dr. Astrid Weyermann Labelling Requirements for IMPs in multinational CTs Page 4 / 71 Requirements in non-EU Member 25 Switzerland .. 25 Japan .. 26 United States .. 26 Summary of Labelling Requirements .. 27 Essential Requirements for the 27 Further Requirements for the 28 4 DECISION PROCESS FOR THE Labelling FLOW 29 5 DECISION PROCESS FOR THE 34 Decision statement for the team ..34 Objectives for the Labelling .. 34 Regulatory Compliance of Labelling information.

5 34 Optimisation of timing ..35 Consideration of costs ..35 Facilitation of manufacturing of the Investigational medicinal product .. 35 Facilitation of clinical trial logistics ..36 Summary of Alternatives .. 37 Number of different labels .. 37 One label for all countries .. 37 One label for each 37 Some labels for several countries 38 Special label for the US .. 38 Timing of activities .. 38 Initiation of the Labelling decision process .. 38 Finalisation of the English core 39 Finalisation of the national 39 Manufacture, Packaging and Labelling .. 39 Regulatory compliance.

6 40 Technical issues of 40 Decision Analysis 41 Organisation of the workflow .. 41 Tasks of involved 42 Regulatory Affairs Department .. 42 Clinical Research 43 Pharmaceutical quality 44 Marketing .. 45 Project 45 Local 45 Summary of Labelling process .. 46 Timing of activities .. 47 Prevention of potential problems ..48 Request for label changes during approval process of the clinical trial .. 48 GMP compliance delay in release of IMP .. 48 Manufacturing .. 49 Clinical trial logistics concerning supply with correctly labelled Investigational medicinal 49 Request for label changes during GMP or GCP inspection.

7 50 6 CONCLUSION .. 51 Dr. Astrid Weyermann Labelling Requirements for IMPs in multinational CTs Page 5 / 71 7 REFERENCES .. 52 8 LIST OF 56 9 ANNEXES .. 57 Tabular overview on definitions .. 57 Labelling Requirements of Annex 13 .. 60 Tabular overview on Labelling Requirements some examples .. 62 Decision Analysis Matrix for the number of labels in a special 65 Templates for Labelling decision 66 Questionnaire and checklist regarding information for the core Labelling .. 66 Example of the draft core Labelling .. 70 Dr. Astrid Weyermann Labelling Requirements for IMPs in multinational CTs Page 6 / 71 1 EXECUTIVE SUMMARY The purpose of regulatory Labelling Requirements for Investigational medicinal products (IMPs) in clinical trials (CTs) is to provide added value regarding Protection of the subjects Identification of the IMP Traceability of the IMP Proper use of the IMP Identification of the trial Proper documentation of the trial The compliance with these Requirements is important for drug development as non-compliance may cause problems during the approval process.

8 The detailed regulatory Requirements for the Labelling of an IMP are described and the differences are discussed for several countries of the ICH regions. It is concluded that especially the divergent national implementation of the EU- Requirements may be regarded as a bureaucratic burden. This may result in increased costs especially in multinational clinical trials without providing additional benefit for subjects and safe conduct of the CT. The regulatory Requirements compiled and summarised by regulatory affairs (RA) provide the basis of the decision process to make the best-balanced choice for the Labelling of the IMP.

9 To assume the responsibility for the Labelling throughout the life cycle of the medicinal product , RA will organise this decision process, which involves close cross-functional communication of several departments and where RA is the interface to all stakeholders of the workflow. A proposal for the organisation of the workflow is described. It can be regarded as a pars pro toto example for several other workflows involving multiple departments and organised by RA. Possible alternatives for the Labelling decision and also measures to avoid potential problems are discussed in general terms focussing on compliance issues, technical and logistic feasibility as well as adherence to timelines.

10 The RA manager optimises the Labelling of IMPs in multinational CTs to reduce the bureaucratic costs and to maximise the added value of the Labelling Requirements . Nevertheless, the question remains how to achieve international harmonisation of the regulatory Requirements for the Labelling of IMPs. Dr. Astrid Weyermann Labelling Requirements for IMPs in multinational CTs Page 7 / 71 2 INTRODUCTION Labelling is an important and integral part of the approval of a medicinal product . This also applies to the Investigational medicinal product (IMP) in clinical trials (CTs). The IMP should be correctly labelled according to the mandatory information required by regulatory authorities.