Fully updated 2nd edition with data for nine countries previously not covered.

This indispensable Scrip report provides you with up-to-date, comprehensive information on current and future adverse drug reaction (ADR) reporting requirements throughout the world.

It is widely known that a fluid regulatory environment governs ADR reporting requirements, with national authorities changing them on a regular basis. Although there is a drive towards international harmonisation, substantial diversity is still present in this area.

This report will guide you through the present administrative labyrinth by providing information about the meeting of reporting requirements in specific countries around the world and the approaches of several multinational companies to current ADR reporting requirements.

Most importantly, it will enable you to plan for the future by providing details of impending changes to reporting requirements.

CONTENTS
LIST OF TABLES
FIGURES
EXECUTIVE SUMMARY
ABBREVIATIONS

CHAPTER 1 INTRODUCTION
1.1 Manufacturers' and regulators' responsibilities
1.2 Harmonisation of global ADR reporting requirements
1.3 Structure of the report

CHAPTER 2 INTERNATIONAL CONFERENCE ON HARMONISATION
2.1 Origin and objectives of ICH
2.2 ICH organisation
2.3 Definitions
2.3.1 Adverse event
2.3.2 Adverse drug reaction
2.3.3 Spontaneous report
2.3.4 Serious AE/ADR
2.3.4.1 Death
2.3.4.2 Life-threatening
2.3.4.4 Significant disability or incapacity
2.3.4.5 Congenital anomaly
2.3.4.6 Medically important adverse events
2.3.5 Unexpected AE/ADR
2.3.6 Unlisted AE/ADR
2.3.7 Clinical trial/study
2.3.8 Comparator
2.3.9 Data lock point
2.3.10 Independent Ethics Committee
2.3.11 Investigational product
2.3.12 Investigator
2.3.13 Investigator's Brochure
2.3.14 Parent-child report
2.3.15 Receiver
2.3.16 Reporter
2.3.17 Sender
2.3.18 Sponsor
2.4 E2A - Clinical Safety Data Management: Definitions and standards for expedited reporting
2.4.1 Background
2.4.2 Scope
2.4.3 Reporting requirements
2.4.4 Minimum criteria for reporting
2.4.5 Report forms
2.4.6 Data elements
2.4.7 Other information
2.4.7.1 Causality assessments
2.4.7.2 Post-study events
2.4.7.3 Managing 'blinded' therapy cases
2.4.7.4 Reactions associated with active comparator or placebo treatment
2.4.7.5 Products with more than one presentation or use
2.4.7.6 Informing investigators and Independent Ethics Committees or Institutional Review Boards
2.4.7.7 Expedited notification of other safety information
2.5 E2B - Clinical Safety Data Management: Data elements for transmission of individual case safety reports
2.5.1 Background
2.5.2 Scope
2.5.3 Data elements
2.5.3.1 Minimum information
2.5.4 Content of the data
2.5.4.1 Section A: Administrative and identification information
2.5.4.2 Section B: Information on the case
2.5.4.3 Parent-child reports
2.5.4.4 Spontaneous abortions (miscarriages)
2.6 E2C - Clinical Safety Data Management: Periodic safety update reports for marketed drugs
2.6.1 Background
2.6.2 Scope
2.6.3 General principles
2.6.3.1 One report for one substance
2.6.3.2 Interval data
2.6.3.3 Frequency of reports
2.6.3.4 International birth date
2.6.3.5 Reference safety information
2.6.3.6 Increased frequency
2.6.3.7 Lack of therapeutic effect
2.6.3.8 Products manufactured and/or marketed by more than one company
2.6.4 Content of the report
2.6.5 Regulatory status and patient exposure
2.6.5.1 Introduction
2.6.5.2 Worldwide market authorisation status
2.6.5.3 Update of regulatory authority or Market Authorisation holder actions taken for safety reasons
2.6.5.4 Changes to reference safety information
2.6.5.5 Patient exposure
2.6.6 Presentation of cases
2.6.6.1 Sources of data
2.6.6.2 Medical terminology
2.6.6.3 Line-listings
2.6.6.4 Summary tabulations
2.6.6.5 Serious unlisted ADRs
2.6.7 Studies
2.6.7.1 Newly analysed company-sponsored studies
2.6.7.2 Targeted new safety studies
2.6.7.3 Published safety studies
2.6.8 Other information
2.6.8.1 Efficacy-related information
2.6.8.2 Late-breaking information
2.6.9 Overall safety evaluation
2.6.10 Concluding statement
2.7 E6 - Good Clinical Practice
2.7.1 Obligations of the investigator
2.7.2 Obligations of the sponsor
2.7.2.1 Safety information
2.7.2.2 Reporting of adverse drug reactions
2.7.3 Investigator's Brochure
2.8 M1 - Medical Terminology Expert Working Group
2.8.1 Objectives
2.8.2 Benefits of a global medical terminology
2.8.3 Scope of MedDRA
2.8.4 Progress with MedDRA
2.8.4.1 Use by regulatory authorities
2.8.4.2 Maintenance and Support Services Organization
2.8.5 Implications for the pharmaceutical industry
2.9 M2 - Electronic Standards for the Transfer of Regulatory Information
2.9.1 Objectives
2.9.2 Recommendations

CHAPTER 3 WORLD HEALTH ORGANIZATION
3.1 Council for International Organizations of Medical Sciences
3.2 CIOMS I - International Reporting of Adverse Drug Reactions
3.2.1 Objectives
3.2.2 CIOMS I report
3.2.2.1 Suspected reactions
3.2.2.2 Unexpected reactions
3.2.2.3 Minimum standard of information
3.2.2.4 Time of reporting
3.2.3 Explanatory notes on completion of the CIOMS form
3.3 CIOMS II - International Reporting of Periodic Drug Safety Update Summaries
3.3.1 Objectives
3.3.2 CIOMS II report
3.3.2.1 Basic principles
3.3.2.2 Scope
3.3.2.3 Frequency of review
3.3.2.4 Content
3.3.2.5 Example of a periodic safety update
3.4 CIOMS Ia - Harmonisation of data elements and data fields for electronic reporting of individual ADR reports
3.5 WHO definitions
3.5.1 Adverse event/experience
3.5.2 Adverse reaction
3.5.3 Serious event
3.5.4 Unexpected adverse reaction
3.5.5 Causality assessments
3.5.5.1 Certain causality
3.5.5.2 Probable/likely causality
3.5.5.3 Possible causality
3.5.5.4 Unlikely
3.5.5.5 Conditional/unclassified causality
3.5.5.6 Inaccessible/unclassifiable causality
3.6 WHO Collaborating Centre for International Drug Monitoring

CHAPTER 4 EUROPEAN UNION
4.1 Regulatory organisations and responsibilities
4.1.1 European Union
4.1.2 European Commission
4.1.3 European Agency for the Evaluation of Medicinal Products
4.1.4 Committee for Proprietary Medicinal Products
4.1.4.1 CPMP guidelines
4.1.4.2 CPMP Pharmacovigilance Working Party
4.1.5 European Pharmacovigilance Research Group
4.2 Legal basis and regulatory framework for ADR reporting
4.2.1 Regulatory framework for investigational products
4.2.1.1 CPMP guideline ICH/377/95
4.2.1.2 Note for Guidance on Good Clinical Practice (CPMP guideline ICH/135/95)
4.2.1.3 CPMP guideline ICH/287/95
4.2.1.4 European Directive on Clinical Trials
4.2.2 Regulatory framework for marketed products
4.2.2.1 Council Regulation 2309/93 and Council Directive 75/319/EEC (as amended)
4.2.2.2 Commission Regulation 540/95
4.2.2.3 Notice to Applicants
4.2.2.4 Volume IX of Rules Governing Medicinal Products in the EU
4.2.2.5 National legislation
4.2.2.6 CPMP guideline ICH/288/95
4.2.2.7 CPMP guideline CPMP/183/97
4.2.3 CPMP guideline CPMP/175/95 ( Role of Member State authorities
4.2.4 Data privacy legislation
4.2.5 Electronic communication of safety information
4.2.5.1 EU Drug Regulatory Authorities Network (EudraNet)
4.2.5.2 EudraWatch
4.2.5.3 Euroscape
4.2.5.4 CPMP guideline ICH/287/95 - Data elements for transmission of individual case safety reports
4.3 Definitions
4.3.1 Adverse event
4.3.2 Adverse reaction
4.3.3 Serious AE/ADRs
4.3.4 Unexpected or unlisted AE/ADRs
4.3.5 Health professional
4.3.6 Valid ADR reports
4.4 General requirements
4.4.1 Responsibilities of the Market Authorisation holder
4.4.2 Responsibilities of the qualified person
4.4.3 Legal liability
4.4.4 Safety databases
4.4.5 Review of scientific literature
4.5 Expedited reporting requirements for investigational products
4.5.1 CPMP guideline ICH/377/95
4.6 Expedited reporting requirements for marketed products
4.6.1 Inconsistencies within the legislation and guidelines
4.6.1.1 Impact of the source of a report
4.6.2 CPMP guideline ICH/377/95
4.6.3 Content of expedited reports
4.6.4 Reporting forms
4.6.5 Scientific evaluations
4.6.5.1 Causality classification
4.6.6 Impact of reported ADRs on the overall safety profile of a product
4.7 Periodic safety update reports
4.7.1 Investigational products
4.7.2 Marketed products
4.7.2.1 Commission Regulation 540/95
4.7.2.2 Frequency of reports
4.7.2.3 'EC' birth date
4.7.2.4 Cross-references
4.7.2.5 Content of reports
4.7.3 Implementation of ICH recommendations (CPMP guideline ICH/288/95)
4.8 Post-authorisation safety studies
4.8.1 Definition of a post-authorisation safety study
4.8.2 Rationale for post-authorisation safety studies
4.8.3 Liaison with regulatory authorities
4.8.3.1 Progress reports
4.9 Future changes to EU requirements for ADR reporting
4.9.1 Amendments to Council Directive 75/319/EEC (as amended)
4.9.2 Volume IX of Rules Governing Medicinal Products in the EU
4.9.2.1 Role of the qualified person
4.9.2.2 Definitions
4.9.2.3 National requirements for expedited ADR reporting
4.9.2.4 Licensing agreements
4.9.2.5 Published literature
4.9.2.6 MedDRA
4.9.2.7 Special situations
4.9.2.8 Content and format of periodic safety update reports
4.9.2.9 Schedule for periodic safety update reports
4.9.2.10 Variations in Summary of Product Characteristics
4.9.2.11 Company-sponsored post-authorisation safety studies
4.9.3 European Directive on Clinical Trials
4.9.3.1 Article 2 (Definitions)
4.9.3.2 Article 13 (Clinical Safety Reporting)
4.9.3.3 Role of EC, Member States and CPMP
4.9.4 Implementation of ICH E2A and E2C guidelines
4.9.5 International medical terminology (MedDRA)
4.9.6 Electronic ADR communication

CHAPTER 5 UNITED KINGDOM
5.1 Legal basis
5.1.1 Statutory Instrument 1994/3144
5.1.1.1 Schedule 1
5.1.1.2 Schedule 3 (offences)
5.1.1.3 Explanatory notes
5.1.2 Guidelines
5.1.3 Data Protection Act 1998
5.2 Medicines Control Agency
5.2.1 Licensing Division
5.2.2 Post-Licensing Division
5.2.3 Strategy for pharmacovigilance
5.2.3.1 Investigational products
5.2.3.2 Marketed products
5.3 Definitions
5.3.1 Relevant medicinal product
5.3.2 Sponsor
5.4 General requirements for pharmaceutical companies
5.5 Investigational products
5.5.1 Expedited reports
5.5.1.1 Report forms and content
5.5.1.2 Treatment codes
5.5.1.3 Causality
5.5.2 Periodic reports
5.5.3 Safety Data Monitoring Committees and line-listings
5.6 Marketed products
5.6.1 Expedited reports
5.6.1.1 Scope
5.6.1.2 Reporting requirements
5.6.1.3 Report forms
5.6.1.4 Black Triangle Scheme
5.6.2 Periodic safety update reports
5.6.3 Reporting of pregnancy outcomes
5.7 Post-authorisation safety studies
5.8 Electronic communication of ADRs
5.8.1 AEGIS
5.8.1.1 Provision of information to companies
5.8.1.2 Provision of information by companies
5.9 Implications for pharmaceutical companies
5.9.1 Offences and penalties
5.9.2 Reporting requirements for marketed products still under clinical investigation
5.9.3 Expedited reports - marketed products
5.9.4 Report forms
5.9.5 Periodic safety update reports
5.9.6 Post-authorisation safety studies
5.10 Future developments

CHAPTER 6 FRANCE
6.1 Legal basis and regulatory framework
6.1.1 Investigational products
6.1.2 Marketed products
6.2 French pharmacovigilance system
6.2.1 Centres Regionaux de Pharmacovigilance
6.2.2 Agence du Medicament
6.2.3 Expert Group on Biomedical Research
6.2.4 Strategy for pharmacovigilance
6.2.4.1 Investigational products
6.2.4.2 Marketed products
6.3 Definitions
6.3.1 Adverse event (clinical trials)
6.3.2 Adverse reaction (clinical trials)
6.3.3 Serious adverse event (clinical trials)
6.3.4 Protocol-related events
6.4 General requirements for pharmaceutical companies
6.5 Investigational products
6.5.1 Expedited reports
6.5.2 Report forms
6.5.3 Managing code breaks
6.5.4 New facts ('fait nouveaux')
6.5.5 Management of specific situations that arise during clinical trials
6.5.5.1 Lack of efficacy
6.5.5.2 Absence of therapy
6.5.5.3 Patient 'wrongly' included
6.5.5.4 Overdose
6.5.5.5 Suicide attempt
6.5.5.6 Hospitalisation
6.5.5.7 Pregnancy
6.6 Marketed products
6.6.1 Expedited reports
6.6.1.1 Imputability assessments
6.6.1.2 Report forms
6.6.2 Periodic safety update reports
6.6.2.1 Schedule for submission
6.6.2.2 Birth dates
6.7 Post-authorisation safety studies
6.8 Responsibilities of health professionals
6.9 Implications for companies
6.9.1 Protocol-related events
6.9.2 Resetting the 'clock'
6.10 Future developments

CHAPTER 7 GERMANY
7.1 Legal basis and regulatory framework
7.1.1 Investigational products
7.1.2 Penalties for non-compliance
7.2 Federal Institute for Drugs and Medical Devices (BfArM)
7.2.1 Strategy for pharmacovigilance
7.3 Definitions
7.3.1 Adverse reaction
7.3.1.1 Lack of efficacy
7.3.1.2 Unexplained death
7.3.1.3 Drug interactions
7.3.2 Serious adverse reaction
7.3.3 Unexpected adverse reaction
7.3.4 Drug abuse
7.3.4.1 Suicide
7.3.5 Drug misuse
7.3.6 Healthcare professionals
7.4 General requirements for pharmaceutical companies
7.4.1 Manufacturers' responsibilities
7.4.2 Commissioner for the Graduated Plan (Stufenplanbeauftragter)
7.5 Expedited reports
7.5.1 Reporting requirements
7.5.1.1 Reporting requirements before marketing authorisation
7.5.2 Minimum criteria for expedited reports
7.5.3 Drug names
7.5.4 Management of ADRs from 'blind' clinical trials
7.5.5 Scientific evaluations
7.5.6 Evaluations of frequency
7.5.7 Report forms
7.5.8 Additional documentation
7.5.9 Consumer reports
7.6 Periodic safety update reports
7.6.1 Schedule for submission
7.6.2 Cases that qualify for inclusion
7.6.3 Content and format of periodic safety update reports
7.6.4 Experience reports
7.6.5 Post-marketing surveillance reports
7.7 Drugs no longer on the market
7.8 Implications for companies
7.8.1 Stufenplanbeauftragter
7.8.2 Notification of all suspected ADRs
7.8.2.1 Definition of an ADR
7.8.3 Emphasis on drug abuse and drug interactions
7.8.4 Scientific evaluations
7.8.5 Management of code breaks
7.8.6 German periodic safety update reports
7.8.6.1 Line-listings
7.8.6.2 Format
7.8.6.3 German birth date
7.9 Future developments

CHAPTER 8 ITALY
8.1 Legal basis and regulatory framework
8.1.1 Penalties for non-compliance
8.2 Italian Ministry of Health
8.2.1 Strategy for pharmacovigilance
8.3 Definitions
8.3.1 Adverse reaction
8.3.2 Serious adverse reactions
8.3.3 Unexpected reaction
8.4 Expedited reports
8.4.1 Investigational products
8.4.2 Marketed products
8.4.2.1 Responsibilities of medical practitioners
8.4.2.2 Pharmaceutical companies
8.4.2.3 Reports from Ministry of Health
8.4.3 Report forms
8.4.4 Causality assessments
8.4.5 'Clock' start
8.5 Periodic safety update reports
8.5.1 Investigational products
8.5.2 Marketed products
8.6 Implications for companies
8.6.1 Time-frame for expedited notifications
8.6.2 Periodic safety update reports
8.7 Future developments

CHAPTER 9 SWEDEN
9.1 Regulatory framework
9.2 Definitions
9.2.1 Minimum information for an ADR report
9.3 General requirements
9.3.1 Responsibilities of the Market Authorisation holder
9.4 Expedited reports
9.4.1 Investigational products
9.4.2 Marketed products
9.4.2.1 Follow-up reports
9.4.3 Report forms
9.5 Periodic safety updates
9.5.1 Investigational products
9.5.2 Marketed products
9.6 Post-authorisation safety studies
9.7 Responsibilities of Swedish healthcare professionals
9.8 Reports from MPA
9.9 Implications for pharmaceutical companies
9.10 Future developments

CHAPTER 10 OTHER EUROPEAN UNION MEMBER STATES
10.1 Austria
10.1.1 Regulatory framework
10.1.2 Definitions
10.1.2.1 Adverse drug reaction
10.1.2.2 Serious reaction
10.1.2.3 Known reaction
10.1.3 Persons responsible for reporting of ADRs
10.1.4 Expedited reporting requirements: investigational products
10.1.5 Expedited reporting requirements: marketed products
10.1.5.1 Domestic reports
10.1.5.2 Foreign reports
10.1.5.3 Evaluation of ADRs
10.1.5.4 Report forms
10.1.6 Periodic safety update reports
10.1.7 Implications for companies
10.2 Belgium
10.2.1 Regulatory framework
10.2.2 Definitions
10.2.3 Responsible person
10.2.4 Expedited reporting requirements: investigational products
10.2.5 Expedited reporting requirements: marketed products
10.2.6 Periodic safety update reports
10.2.7 Implications for companies
10.3 Denmark
10.3.1 Regulatory framework
10.3.2 Definitions
10.3.2.1 Side effect
10.3.2.2 Serious side effects
10.3.2.3 Minimum information for reporting
10.3.3 Expedited reports
10.3.3.1 Investigational products
10.3.3.2 Marketed products
10.3.3.3 Report forms
10.3.4 Periodic reports: investigational products
10.3.5 Periodic safety update reports: marketed products
10.3.5.1 Schedule for submission
10.3.5.2 Case selection for line-listings
10.3.6 Reports from DMA
10.3.7 Implications for companies
10.4 Finland
10.4.1 Regulatory framework
10.4.2 Definitions
10.4.3 General requirements
10.4.4 Reporting requirements: investigational products
10.4.5 Reporting requirements: marketed products
10.4.5.1 'Clock' start
10.4.5.2 Product licence renewal
10.4.6 Implications for companies
10.5 Greece
10.5.1 Regulatory framework
10.5.2 Definitions
10.5.3 Responsible person
10.5.4 Expedited reporting requirements
10.5.4.1 Forms
10.5.5 Periodic safety update reports
10.5.5.1 Schedule for submission
10.5.5.2 Case selection for line-listings
10.5.5.3 Presentation of ADRs
10.5.5.4 Product licence renewal
10.5.5.5 EC birth dates
10.5.6 Implications for companies
10.6 Ireland
10.6.1 Regulatory framework
10.6.1.1 Irish Medicines Board
10.6.2 Definitions
10.6.3 Responsible person
10.6.4 Expedited reporting requirements: investigational products
10.6.5 Expedited reporting requirements: marketed products
10.6.5.1 Report forms
10.6.6 Periodic safety update reports
10.6.7 Company-sponsored post-authorisation studies
10.6.8 Pregnancy registries
10.6.9 Implications for companies
10.7 Luxembourg
10.8 The Netherlands
10.8.1 Legal basis and regulatory framework
10.8.2 Definitions
10.8.2.1 Adverse reaction
10.8.2.2 Serious adverse reaction
10.8.2.3 Unexpected adverse reaction
10.8.3 Drug Safety Officer
10.8.4 Expedited reports
10.8.4.1 Report forms
10.8.4.2 Causality assessments
10.8.5 Periodic safety update reports
10.8.6 Implications for companies
10.9 Portugal
10.9.1 Legal basis and regulatory framework
10.9.2 Definitions
10.9.2.1 Adverse reaction
10.9.2.2 Serious adverse reaction
10.9.2.3 Unexpected adverse reaction
10.9.2.4 Valid notification
10.9.3 General requirements
10.9.4 Reporting requirements: clinical trials
10.9.5 Reporting requirements: marketed products (including pending authorisations)
10.9.5.1 Expedited reports
10.9.5.2 Periodic safety update reports
10.9.6 Report forms
10.9.7 Implications for companies
10.10 Spain
10.10.1 Regulatory framework
10.10.2 Definitions
10.10.3 Drug Safety Officer
10.10.4 Minimum criteria for reporting
10.10.5 Expedited reporting requirements: investigational products
10.10.6 Expedited reporting requirements: marketed products
10.10.6.1 Report forms
10.10.7 Periodic safety update reports
10.10.8 Post-authorisation safety studies
10.10.9 Implications for companies

CHAPTER 11 UNITED STATES OF AMERICA
11.1 Legal basis
11.2 Regulatory framework
11.3 Food and Drug Administration
11.3.1 MedWatch
11.4 Definitions
11.4.1 General terms
11.4.1.1 Affiliate
11.4.1.2 Applicant
11.4.1.3 Contract research organisation
11.4.1.4 Sponsor
11.4.2 Safety-related terms
11.4.2.1 Adverse drug experience
11.4.2.2 Adverse drug reaction
11.4.3 Serious adverse drug experience
11.4.4 Unexpected/unlabelled adverse drug experience
11.4.4.1 IND definition
11.4.4.2 NDA definition
11.4.4.3 Class-related effects
11.4.5 Death
11.4.5.1 Death as an adverse drug experience
11.4.5.2 FDA guideline (1992)
11.4.5.3 Interpretation of FDA guidance on reporting deaths
11.5 Reporting requirements for INDs
11.5.1 Review of safety information
11.5.2 IND safety reports
11.5.2.1 Seven-day reports
11.5.2.2 Fifteen-day reports
11.5.2.3 Expedited notification of ADRs from non-IND sources
11.5.2.4 IND safety reports for marketed products
11.5.2.5 Management of follow-up information
11.5.2.6 Reporting format or frequency
11.5.3 IND annual reports
11.5.3.1 Individual study information
11.5.3.2 Summary information
11.5.3.3 Other information
11.5.4 Transfer of obligations to a contract research organisation
11.6 Reporting requirements for marketed products
11.6.1 Obligations of the applicant
11.6.2 Obligations for non-applicants
11.6.3 Fifteen-day reports
11.6.3.1 Follow-up reports
11.6.4 Periodic reports
11.6.4.1 Form 3500As
11.6.4.2 Index line-listing of Form 3500As
11.6.4.3 Narrative summary and analysis
11.6.4.4 Narrative discussion of action taken
11.6.5 Post-marketing ADR reports: other considerations
11.6.5.1 Reporting of events on another company's products
11.6.5.2 Data elements for a post-marketing safety report
11.6.5.3 Scientific literature
11.6.5.4 Post-marketing studies
11.6.5.5 Individual case reports based on solicited information
11.6.5.6 Overdose reports
11.6.5.7 Lack of effect reports
11.6.5.8 Paediatric patients
11.6.5.9 Increased frequency reports
11.6.5.10 Patient and reporter privacy
11.6.5.11 Record keeping
11.6.5.12 Withdrawal of clearance for marketing
11.6.5.13 Disclaimer
11.6.5.14 NDA-Field Reports
11.7 Future developments
11.7.1 Definitions and data sets
11.7.2 Periodic safety update reports
11.7.2.1 IND annual reports
11.7.2.2 Marketed products
11.7.3 Electronic communication of safety information
11.7.4 International medical terminology

CHAPTER 12 CANADA
12.1 Legal basis and regulatory framework
12.2 Health Protection Branch
12.2.1 Adverse Drug Reaction Monitoring Program
12.2.1.1 Regional Centre Program
12.2.1.2 Expert Advisory Committee on Pharmacovigilance
12.2.2 Strategy for pharmacovigilance
12.3 Definitions
12.3.1 Drug
12.3.2 Adverse drug event
12.3.3 Adverse drug reaction
12.3.4 Serious ADR
12.3.5 Unexpected ADR
12.4 General requirements
12.4.1 Reportable ADRs
12.4.1.1 Lack of efficacy
12.4.1.2 Consumer reports
12.5 Expedited reports
12.5.1 Minimal criteria for an ADR report
12.5.2 Investigational products
12.5.2.1 Blind reports
12.5.3 Premature closure of a trial
12.5.4 Marketed products
12.5.4.1 Reporting requirements
12.5.4.2 Post-marketing studies
12.5.5 Report forms
12.6 Periodic reporting requirements
12.6.1 Annual IND Reports
12.6.1.1 Timing of submission
12.6.1.2 Content
12.6.2 Periodic safety update reports
12.6.2.1 Timing of submission
12.6.2.2 Content of PSURs
12.6.2.3 Summary line-listing
12.6.2.4 Critical analysis
12.6.2.5 Recommended actions
12.7 Implications for companies
12.7.1 Expedited reports
12.7.2 Periodic reports
12.7.2.1 Annual IND Reports
12.7.2.2 Periodic safety update reports
12.8 Future developments

CHAPTER 13 JAPAN
13.1 Legal basis and regulatory framework
13.1.1 Investigational products
13.1.2 Marketed products
13.2 Ministry of Health and Welfare
13.3 Definitions
13.3.1 Serious AE/ADR
13.3.2 Severe AE/ADRs
13.3.3 Unexpected ADR
13.4 Expedited reports
13.4.1 Investigational products
13.4.1.1 Effect of investigational/submission status
13.4.1.2 Causality assessments
13.4.2 Marketed products
13.4.2.1 Infections
13.4.3 Measures taken abroad
13.4.4 Destination for reports
13.5 Periodic safety update reports
13.6 Implications for companies
13.7 Future developments

CHAPTER 14 REST OF WORLD
14.1 Australia
14.1.1 Regulatory framework
14.1.2 Definitions
14.1.2.1 Serious reaction
14.1.2.2 Unexpected reaction
14.1.3 Reporting requirements: investigational products
14.1.3.1 Expedited reports
14.1.3.2 Managing blind cases
14.1.3.3 Annual reports
14.1.3.4 Clinical Trial Notification Scheme
14.1.3.5 Special Access Scheme
14.1.4 Reporting requirements: marketed products
14.1.4.1 Expedited reports
14.1.4.2 Periodic safety update reports
14.1.5 Report forms
14.1.6 Foreign reports
14.1.7 Implications for companies
14.2 New Zealand
14.2.1 Regulatory framework
14.2.2 Definitions
14.2.3 Reporting requirements: investigational products
14.2.3.1 Investigators
14.2.3.2 Sponsors
14.2.4 Reporting requirements: marketed products
14.2.4.1 Reporting of adverse reactions
14.2.4.2 Reporting of substantial untoward effects
14.2.5 Implications for companies
14.3 South Africa
14.3.1 Regulatory framework
14.3.2 Definitions
14.3.2.1 Adverse event (or experience)
14.3.2.2 Adverse reaction
14.3.2.3 Serious AE/ADR
14.3.2.4 Unexpected reaction
14.3.2.5 Healthcare professional
14.3.2.6 Minimum information for ADR reports
14.3.3 Expedited reporting requirements
14.3.3.1 Investigational products
14.3.3.2 Marketed products
14.3.3.3 Report forms
14.3.4 Periodic safety update reports
14.3.4.1 Investigational products
14.3.4.2 Marketed products
14.3.5 Implications for companies
14.4 Norway
14.4.1 Regulatory framework
14.4.2 Definitions
14.4.2.1 Serious/not serious
14.4.2.2 Causality assessments
14.4.2.3 Frequent ADR
14.4.3 Reporting requirements: investigational products
14.4.4 Reporting requirements: marketed products
14.4.4.1 Expedited reports
14.4.4.2 Periodic safety update reports
14.4.5 Information from NMCA to the pharmaceutical industry
14.4.6 Implications for companies
14.5 Czech Republic
14.5.1 Regulatory framework
14.5.2 Definitions
14.5.2.1 Investigational product
14.5.2.2 Adverse event
14.5.2.3 Adverse drug reaction
14.5.2.4 Serious adverse event
14.5.2.5 Unexpected ADR
14.5.3 General requirements
14.5.3.1 Clinical trials
14.5.3.2 Marketed products
14.5.4 Reporting requirements: investigational products
14.5.4.1 Expedited reports
14.5.4.2 Report forms and content
14.5.4.3 Annual reports
14.5.5 Reporting requirements: marketed products
14.5.6 Implications for companies
14.6 Hungary
14.6.1 Regulatory framework
14.6.2 Definitions
14.6.3 Reporting requirements: clinical studies
14.6.4 Reporting requirements: marketed products
14.6.4.1 Expedited reports
14.6.4.2 Periodic safety update reports
14.6.5 Implications for companies
14.7 Poland
14.7.1 Regulatory framework
14.7.2 Definitions
14.7.3 Reporting requirements: investigational products
14.7.4 Reporting requirements: marketed products
14.7.4.1 Product licence renewal
14.7.4.2 Report format
14.7.5 Implications for companies
14.8 Switzerland
14.8.1 Regulatory framework
14.8.1.1 Schweizerische Arzneimittel-Nebenwirkungs-Zentrale (SANZ)
14.8.2 Definitions
14.8.3 Expedited reporting requirements: investigational products
14.8.4 Expedited reporting requirements: marketed products
14.8.5 Periodic safety update reports
14.8.6 Implications for companies

CHAPTER 15 MEETING GLOBAL ADR REPORTING REQUIREMENTS
15.1 Factors that contribute to the diversity of ADR reporting requirements
15.2 General requirements
15.2.1 Qualified person
15.2.2 Collection and collation of adverse reaction data
15.3 Definitions
15.3.1 Serious
15.3.2 Healthcare professional
15.3.3 Valid report
15.3.4 Scientific literature
15.3.5 Unexpected ADRs
15.3.5.1 Definition of the term
15.3.5.2 Interpretation of the term
15.3.5.3 Management of the term 'unexpected'
15.3.5.4 When is death an 'unexpected' AE/ADR?
15.3.6 Sponsorship of clinical trials
15.3.6.1 Notification of ADRs to regulatory authorities
15.3.6.2 Collection of ADRs from clinical trials conducted by external organisations
15.4 Expedited ADR reports
15.4.1 USA
15.4.2 Japan
15.4.3 European Union
15.4.3.1 Investigational products
15.4.3.2 Impact of ICH E2A
15.4.3.3 Marketed products
15.4.4 Report forms
15.4.5 Meeting global expedited reporting requirements
15.5 Periodic drug safety updates
15.5.1 Investigational products
15.5.2 USA
15.5.3 Japan
15.5.4 European Union
15.5.4.1 EC birth date
15.5.5 Meeting global periodic reporting requirements
15.6 Process implications
15.6.1 Case study: Zeneca Pharmaceuticals
15.6.2 Business process re-engineering
15.6.2.1 Objectives
15.6.2.2 Opportunities for improvement
15.6.2.3 The new process
15.6.2.4 Quality-on-time

APPENDIX I CONTENT OF SERIOUS SUSPECTED ADR REPORTS - COMPARISON OF DRAFT NOTICE TO APPLICANTS WITH ICH E2A GUIDELINE

APPENDIX II SAMPLE LINE-LISTINGS

APPENDIX III EXAMPLE OF A SUMMARY TABULATION (ICH E2C)

APPENDIX IV CASE SELECTION FOR EXPEDITED REPORTING IN EU

APPENDIX V FRENCH IMPUTABILITY METHOD

REFERENCES

PUBLISHED: January 1999
REF: BS980E
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