Good Clinical Practice Guide

The Good Clinical Practice Guide is a brand new publication covering the legislation, guidance and good practice that relates to the conduct of clinical trials of medicinal products for human use in the UK. Detailed and authoritative, this guide will provide practical advice about implementing the principles of Good Clinical Practice within the context of the clinical trial regulatory framework in the European Union. Written and produced by the MHRA, this is the only guide on Good Clinical Practice available within Europe which has been produced by a regulatory agency. This title is aimed at any individual and/or organisation involved in conducting clinical trials with medicines in the UK, including both commercial and non-commercial sponsors and hosts of clinical trials, as well as contract research organisations, clinical research consultants and other niche providers. The guide references European legislation and guidance as well as international standards, so will also be relevant to organisations conducting trials across Europe and beyond. © Copyright 2012 Foreword Acknowledgements Feedback Abbreviations​ Preface Introduction Chapter 1 Sponsor oversight 1.1 Sponsors 1.2 Clinical trial authorisations and research ethics committee opinion 1.3 Good Clinical Practice and conduct of clinical trials 1.4 Pharmacovigilance 1.5 Manufacture, assembly, importation and labelling of IMP 1.6 Trial/project management 1.7 Chapter legislative references Chapter 2 Clinical trial authorisations 2.1 Legal definition of a clinical trial 2.2 2.3 Clinical trial authorisation applications – assessment and amendments 2.4 Risk-adapted approach to the management of clinical trials 2.5 Clinical trial authorisation applications requiring expert advice 2.6 Voluntary Harmonisation Procedure 2.7 Chapter legislative references Chapter 3 Ethical review 3.1 Appointment of research ethics committees 3.2 Application to research ethics committees 3.3 Informed consent 3.4 Amendments 3.5 Safety reporting to the research ethics committee 3.6 Other required reports to the research ethics committee 3.7 Retention of documentation by the research ethics committee 3.8 GCP inspections and ethical review 3.9 Chapter legislative references Chapter 4 Key trial documentation 4.1 Expectations and legislative requirements 4.2 Generation of key trial documentation 4.3 Updating and amending key trial documents 4.4 Version control 4.5 Cross-checking and quality control 4.6 Sponsor oversight of third-party key trial documents 4.7 Key trial document considerations 4.8 Chapter legislative references Chapter 5 Pharmacovigilance for clinical trials 5.1 Relevant terminology 5.2 Introduction to safety reporting 5.3 Adverse events – recording and notification 5.4 Serious adverse events 5.5 Suspected unexpected serious adverse reactions 5.6 Assessments and information required for reporting purposes 5.7 Considerations for blinded trials 5.8 Ongoing safety evaluation 5.9 Data monitoring committees/data safety monitoring boards 5.10 Safety reporting requirements for nIMPs 5.11 Out-of-hours medical cover 5.12 Investigator-initiated trials 5.13 Specific safety requirements for trials of advanced therapy products 5.14 Pharmacovigilance data collection 5.15 Development safety update reports 5.16 Chapter legislative references Chapter 6 Investigational medicinal products 6.1 Requirements for a manufacturing authorisation for investigational medicinal products 6.2 Exemptions from the need for an MIA(IMP) 6.3 Declaration, certification and release 6.4 Contracting-out activities 6.5 Active pharmaceutical ingredient 6.6 Blinding 6.7 Labelling 6.8 Manufacture or reconstitution 6.9 The use of commercial supply in clinical trials 6.10 Supplies for investigator-initiated trials 6.11 Product recall 6.12 Non-investigational medicinal products 6.13 Drug accountability 6.14 Storage and distribution of investigational medicinal product 6.15 Administration at home 6.16 Use of trial material after trial completion 6.17 Prescribing and dispensing 6.18 Documentation retention 6.19 Chapter legislative references Chapter 7 Monitoring 7.1 Introduction to monitoring 7.2 Monitoring overview 7.3 Monitoring strategy 7.4 Monitoring personnel 7.5 Monitoring activities 7.6 Output from monitoring 7.7 Source data verification and case report form management 7.8 Chapter legislative references Chapter 8 Data management 8.1 Overview of the data management process 8.2 Case report forms and data collection tools 8.3 Clinical database 8.4 Data capture 8.5 Data validation 8.6 Database/dataset lock 8.7 Chapter legislative references Chapter 9 Statistics 9.1 Statistical processes, procedures and records 9.2 Statistics personnel 9.3 Trial and protocol design 9.4 Statistical input to case report form design and data management activities 9.5 Randomisation and blinding 9.6 Statistical analysis plan 9.7 Statistical programming and analysis 9.8 Chapter legislative references Chapter 10 Trial master file and archiving 10.1 Requirement for a trial master file 10.2 Trial master file organisation 10.3 Content of the trial master file 10.4 Control of the trial master file 10.5 Electronic trial master file 10.6 MHRA GCP inspection of trial master files 10.7 Archiving 10.8 Chapter legislative references Chapter 11 Investigator sites 11.1 Research site 11.2 Investigator site research team 11.3 Site set-up 11.4 During the study 11.5 Study documentation 11.6 Chapter legislative references Chapter 12 Phase I clinical trials 12.1 Introduction to Phase I clinical trials 12.2 Voluntary MHRA Phase I Accreditation Scheme 12.3 Authorisation and ethical opinion for a Phase I clinical trial 12.4 Contracts, agreements and insurance 12.5 Risk assessment and contingency planning 12.6 Dose escalation in clinical trials 12.7 IMP management 12.8 Facilities and equipment 12.9 Planning and resources 12.10 Training 12.11 Emergency procedures 12.12 Subject identification and recruitment 12.13 Chapter legislative references Chapter 13 Clinical trial samples – analysis and evaluation 13.1 Organisation of laboratory work 13.2 Sample transportation, receipt and storage 13.3 Processing samples from clinical trials 13.4 Laboratory facilities and equipment 13.5 Reporting and archiving of data 13.6 Maintaining quality within the laboratory 13.7 The trial subject 13.8 Chapter legislative references Chapter 14 Quality systems 14.1 Quality system structure 14.2 Training 14.3 Quality control 14.4 Quality assurance 14.5 Computer system validation 14.6 Chapter legislative references Annexes Annex 1 Introduction to GCP inspections A.1.1 Legal basis for inspections A.1.2 MHRA GCP inspectors A.1.3 Types of GCP inspections A.1.4 Scope of GCP inspections A.1.5 Inspection schedule A.1.6 Phases of the inspection process A.1.7 Responding to findings A.1.8 Close-out of the inspection A.1.9 Follow-up for serious inspection findings A.1.10 Re-inspections A.1.11 Tips for preparing for a competent authority inspection Annex 2 Relevant legislation and guidance A.2.1 European legislation A.2.2 UK legislation A.2.3 Guidance documents and other useful reference texts Annex 3 Advanced therapy investigational medicinal product trials A.3.1 Considerations for advanced therapy investigational medicinal product trials A.3.2 Annex legislative references Annex 4 Considerations for use of electronic systems in clinical trial management A.4.1 What is an IRT system? A.4.2 Setting up an IRT system A.4.3 Use of an IRT system A.4.4 Maintenance of an IRT system A.4.5 What to do when the IRT system is unavailable A.4.6 Close-down of an IRT system A.4.7 Annex legislative references Glossary Index Table Index Figure Index