Review of the management of adverse events associated with Panvax and Fluvax

Appendix III - International arrangements for post-market surveillance and monitoring of vaccines

Page last updated: April 2015


Regulatory Agency and Relevant Committees Passive AEFI ReportingAgency responsible for collation of AEFI Reports and Relevant CommitteesOther routine
Pharmacovigilance (PV) activities
Additional non-routine activitiesSafety signal identification and follow upAdvisory Body for Vaccination Program
GlobalWorld Health Organization (WHO)

Global Advisory Committee on Vaccine Safety

Council of International Organized Medical Societies (WHO-CIOMS) Vaccine Pharmaco-vigilance (PV) Working Group
The WHO Programme for International Drug Monitoring (IDM)

Covers both medicines and vaccines

104 countries participate
WHO Collaborating Centre for International Drug Monitoring Uppsala, Sweden (the Uppsala Monitoring Centre or UMC)

VigiBase = WHO Individual Case Safety Reports (ICSR) database = global repository of AEFI data
Global capacity building, harmonised tools, education and training

Brighton Collaboration – standardised definitions of AEFIs

Vaccine Safety Blueprint Project (with funding from the Gates Foundation)
– supports developing countries to develop PV systems
European UnionEuropean Medicines Agency (EMA)

Legal basis is in EC regulations and directives

Legislation describes respective obligations of marketing authorisation holders (MAHs) and competent authorities (CAs) in each member state to set up a system to collect, collate and evaluate information about suspected adverse reactions (distinguishes between events and reactions)

Intensive information exchange is needed between MAHs, CAs of members States and the EMA

Guidance is Vol 9A
PV obligations apply to all medicinal products and legislation does not distinguish between vaccines and other medicinal products
CanadaHealth Canada

The Biologics and Genetic Therapies Directorate and the Marketed Health Products Directorate

Role in registration of products and in PV, including recalls and advisories
Canadian Adverse Events Following Immunization Surveillance System (CAEFISS)

Specific for vaccines
(MedEffect is used for drugs)

Voluntary (except for 4 provinces with mandatory reporting requirements) - health care providers report to local, provincial and/or territorial public health authorities events they feel are temporarily associated with an immunization

Reports are forwarded by the provinces and territories to the Vaccine Safety Unit (VSU) of the Public Health Agency of Canada (PHAC) for aggregation

Particular events of interest are included in the national reporting form used (with modifications) by all Ps and T

Manufacturers are legally required to report all adverse events directly to Health Canada (previously to PHAC but now to regulator)

Data to WHO IDM programme
Vaccine Safety Unit (VSU) of the Centre for Immunization and Respiratory Diseases (CIPD) of the Public Health Agency of Canada (PHAC)

Advisory Committee on Causality Assessment (ACCA) reviews all case reports of severe or unexpected AEs. Uses WHO-UMC criteria to assess causality
Immunization Monitoring Program ACTive (IMPACT) – active sentinel surveillance in 12 tertiary care paediatric hospitals across Canada

AEs reported from medical practitioners directly to Health Canada. These data are also stored in the AEFI database at the PHAC

Covers AEFIs, vaccination failures and selected IDs. Represents over 2,000 hospital beds and 75,000 childhood admissions (over 90% of all paediatric tertiary admissions). At each centre a nurse monitor and chief investigator perform active case-finding based on regular review of admission records. Assisted by a multidisciplinary network
To calculate rates, lot specific vaccine distribution data are obtained from vaccine manufacturers and used as an approximation of doses administered. Limited reliability but useful for signal generation

If further estimates are needed they are obtained from vaccine coverage studies

If signal detected, action is taken as appropriate, either immediate or through additional scientific investigation to confirm or refute the signal
National Advisory Committee on Immunization (NACI)

NACI reports to the Chief Public Health Officer of Canada and works with departmental staff of the CIDPC of the PHAC

All NACI recommendations are published 4 yearly in the Canadian Immunization Guide (CIG); updates in the Canadian Communicable Diseases Report

The CIG provides information on nature of adverse events with specific vaccines

(systems largely governed by relevant EU legislation)
Irish Medicines Board (IMB)

A Board appointed by Minister for Health and Children

(the EU National Competent Authority for medicines in Ireland)

Role in both registration and pharmaco-vigilance

The Advisory Committee for Human Medicines
Medicines and vaccines

Voluntary - health professionals and consumers. HP reporting encouraged with regular reminders and updates

Mandatory - pharmaceutical companies
Irish Medicines Board (IMB)National Immunisation Advisory Committee (NIAC) of the Royal College of Physicians of Ireland

Health Protection Surveillance Centre

National Immunisation Office of the Irish Health Service Executive
New ZealandThe New Zealand Medicines and Medical Devices Safety Authority

A business unit of the Ministry of Health

Role in both registration and pharmaco-vigilance

Medicines Adverse Reactions Committee (MARC) - a Ministerial Advisory Committee
Medicines and Vaccines

Voluntary - health professionals and consumers are encouraged to report

Reports also received from Coroners, the Accident Compensation Commission and pharmaceutical companies

Reports of AEs can be submitted via
- Reporting card
CARM website (separate online vaccine AE reporting form)
- Electronic (embedded in GP practice patient management systems)
- Phone to Medical Assessors at CARM
Medsafe contracts the collation, review and analysis of spontaneous reports to the Centre for Adverse Reactions Monitoring (CARM) of the New Zealand Pharmaco-vigilance Centre at the University of Otago in Dunedin

CARM reports to Medsafe and works with Medsafe to analyse all information for safety signals

No other bodies are responsible for the collection or review of the case reports
United KingdomMedicines and Healthcare products Regulatory Agency (MHRA)

An Executive Agency of the Department of Health

Role in both registration and pharmaco-vigilance

Commission on Human Medicines (CHM)

Biologicals and Vaccines Expert Advisory Group

Pharmaco -vigilence Expert Advisory Group
“Yellow Card” System (both medicines and vaccines)

Voluntary reporting health professionals and public. HPs are encouraged to report. Education and training through regional Yellow Card centres

Mandatory - pharmaceutical companies
Medicines and Healthcare products Regulatory Agency (MHRA)

Case reports collated into the ADR database

Analyse using clinical judgement and specialised IT software and statistical analyses, including dis-proportionality analyses
Evaluation of clinical and epidemiological studies, published medical literature, information from pharmaceutical companies and other regulatory agencies

General Practice Research Database (GPRD)
An electronic data source of information from over 590 practices in the UK covering about 5 million patients with record linkage. Used to conduct ad hoc evaluation and research
Risk management strategy defined in advance of rollout of new vaccine. May include stimulating reporting, and/or conducting real-time observed/expected (O/E) analyses of AESIs

Active surveillance and/or commissioned research on a case by case basis
Epidemiological studies through the GPRD system

Dedicated ‘on-line’ reporting system implemented for pandemic H1N1

Independent advice from CHM and subcommittees, EU Member States and EMA

Information sharing with international counterparts, including TGA
Joint Committee on Vaccination and Immunisation
- Independent expert advisory committee that advises Ministers on matters relating to the provision of vaccination and immunisation services

Immunisation policy set by Department of Health/ Health Protection Agency (DoH/HPA)

United States of AmericaFood and Drug Authority (FDA)

Agency within the Department of Health and Human Services

Role in both registration and pharmaco-vigilance

Vaccines and Related Biological Products Advisory Committee
Vaccine Adverse Events Reporting System (VAERS)

Mandatory reporting of events in the Reportable Events Table by health care providers. Legal authority is the National Childhood Vaccine Injury Act of 1986

Health care professionals encouraged to report any clinically significant or unexpected event

Anyone can report. Consumers are advised to seek assistance from their health care professional in completing the form

The primary objectives of VAERS are to:
- Detect new, unusual, or rare vaccine adverse events (VAEs)
- Monitor increases in known adverse events;
- Identify potential patient risk factors for particular types of adverse events;
- Identify vaccine lots with increased numbers or types of reported adverse events; and
- Assess the safety of newly licensed vaccines
Immunization Safety Office (ISO) of the Centers for Disease Control and Prevention (CDC)

Agency within the Department of Health and Human Services

Jointly with FDA

Both FDA and CDC review the case data
Vaccine Safety Datalink project (VSD) run by CDC
Eight large managed care organisations – uses data linkage to analyse vaccine-related and clinical information for more than 7 million people

Brighton Collaboration Standardised definitions of AEFIs

Rapid Cycle Analysis (RCA)
De-identified data, updated weekly, from eight managed care organisations used for active surveillance of AEFI in near real time for newly licensed vaccines and new vaccine recommendations. Potential AEs - identified through premarketing studies, early analysis from VAERS and published scientific articles - are monitored by comparing their rate of occurrence in people who have received a vaccine with the rate of occurrence in a similar group of people who have not received that vaccine. If rate is significantly higher, then a formal epidemiological study is done
Clinical Immunization Safety Assessment (CISA) Network
Collaboration between CDC (ISO) and 6 academic centres

To investigate patho-physiologic mechanisms and biological risks of AEFIs. Has a registry of people who have had an AEFI and a repository to store specimens for future studies

The VSD can also be used for planned immunisation studies to detect rare adverse events when new vaccines are licensed or when safety question arises. A number of Priority Studies using VSD data are currently underway
Additional case data may be obtained from person reporting the event and/or their health care providerAdvisory Committee on Immunization Practices (ACIP)

Members are selected by the Secretary of the U. S. Department of Health and Human Services to provide advice and guidance to the Secretary, the Assistant Secretary for Health, and the Centers for Disease Control and Prevention (CDC) on the control of vaccine-preventable diseases

The Committee develops written recommendations for the routine administration of vaccines to children and adults in the civilian population; recommendations include age for vaccine administration, number of doses and dosing interval, and precautions and contraindications. The ACIP is the only entity in the federal government that makes such recommendations

National Vaccine Program
National Vaccine Advisory Committee (NVAC)
provides advice on matters related to program responsibilities to the Director of the National Vaccine Program within the Department of Health and Human Services

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