Outlook of the health system in Australia and the systems in place for safety reporting.

1. Presented by Saeeda A. Hasan, BSc.
Fellow Student in Clinical Research, Drug Safety and Pharmacovigilance at AAPS
Clinical Research Program Director and Professor: Dr. Peivand Pirouzi
AAPS, 2016
PHARMACOVIGILANCE IN AUSTRALIA

2. Courtesy of Dr. Peivand Pirouzi

3. • Every year Australia spends more on its health $121.4 billion on health in
2009-10 which accounted for 9.4% of total spending on all goods and
services in the economy. This averaged out to $5479 per person
• As a proportion of GDP, Australia spending in 2009 was much less than that
of the United Sates (17.4%), slightly less than the UK (9.8%), New Zeeland
(10.3%) and Canada (11.4%) and close to the OECD median (9.6%)

4. HEALTH CARE SYSTEM IN AUSTRALIA
http://www.aihw.gov.au/australias-health/2014/health-system/

5. • Chronic diseases are the leading cause of illness, disability and
death in Australia, accounting for 90% of all deaths in 2011
• Over 140 000 people die each year including 100 000 whose
deaths are expected because of a terminal illness
• Mental health-related issues are not a major cause of death, but
they do cause significant ill health and disability in the Australian
population

6. • Thalidomide embryopathy in 1961
• Several countries set up committees of experts to review applications to
market new drugs: Australian Drug Evaluation Committee (1963)
• National Adverse Drug Reaction Spontaneous Monitoring Schemes in 1964
and setting up of ADRAC in 1970
• WHO Collaborative program for international Drug Monitoring in which
Australia was one of the ten countries that took part in the feasibility study in
1968.
• The health professionals were educated to directly report any ADRs
• Feedback to the health care professionals
• ADR Bulletin

7. • The Therapeutic Goods Administration (TGA) is part of the Regulatory
Services Group in the Australian Government Department of Health.
• The Regulatory Services Group includes:
• Therapeutic Goods Administration (TGA)
• --- established under the Therapeutic Goods Act 1989
• Office of the Gene Technology Regulator (OGTR)
• Office of Chemical Safety (OCS)

8. • Australian Adverse Drug Reactions Advisory Committee (ADRAC)
• Comprises of a variety of medical experts
• Meets 8 times every year
• Provides ongoing review of safety issues from individual reports to
national and international alerts
• Quality is assured by two processes
• Formalized assessment
• Peer review
• The essential steps involve analysis of the evidence, identification of
options and policy decision making

9. PHARMACOVIGILANCE GUIDELINES
• Guideline for pharmacovigilance responsibilities for sponsors of registered (authorized for market)
medicines that includes adverse reaction reporting and reporting requirements in special situations.
• Where European Union (EU) guidelines adopted in Australia include references to EU legislation
(including EC Directives and Regulations)
• The requirements contained in the referenced EU legislation are not applicable to the evaluation of
prescription medicines by the TGA
• The Australian legislative requirements applying to prescription medicines are contained in the
Therapeutic Goods Act 1989 and the Therapeutic Goods Regulations 1990, as well as in various
legislative instruments such as Therapeutic Goods Orders, Notices and Determinations
• TGA has formally adopted the EU Guideline Volume 9A format (EU-RMP) for risk management
plans (Guideline on GVP Module V – Risk management systems (Rev 1): adopted by TGA 10 April
2014
• Australian requirements take precedence in situations where details of processes and requirements
differ between the Australian and European/ICH guidelines.
• Spontaneous Reporting: “Australian guideline for pharmacovigilance responsibilities of sponsors for
registered medicines regulated by Drug Safety and Evaluation Branch,” July 2003, Amended May
2005.
• Clinical Safety Reporting: “Access to unapproved therapeutic goods – clinical trials in Australia,”
Oct 2004.

10. • Guideline on GPV Module V – Risk management systems (Rev 1): The TGA will accept all
EU RMP modules relating to advance therapy medicinal products for products not
classified as biologics in Australia
• In line with changes in the EU, updated EU RMPs should be submitted at the request of
the TGA and whenever the EU RMP is modified as a result of new information which may
change the risk-benefit of the product or as a result of an important pharmacovigilance or
risk minimisation milestone being reached
• TGA is adopting the Guideline on GPV) module VII Periodic Safety Update Reports (Rev
1), including the EU specific requirements (adopted by TGA in 2 Oct 2002). The frequency
of PSUR submissions may not align with that in the EU and the usual requirement in
Australia is that PSURs are to be submitted annually for 3 years post registration or after
changes to the registration, as specified in the approval letter. Also all the sections are not
being adopted such as reference to European legislation, regulatory bodies and processes
do not apply in Australia
• Guideline on conduct of PV for medicines used by the pediatric population (adopted by
TGA 16 March 2009)
• ICH guideline E2C (R2) on periodic benefit-risk evaluation report (PBRER): adopted by
TGA 7 June 2005
• ICH Topic E 2 E Note on Guidance on Planning Pharmacovigilance Activities

11. ADR REPORTING
• Of 10,000 reports annually:
• 94% involve prescription medicines
• 3% each OTC and complementary medicines
• 80-90% from GPs, hospitals, industry, and State Health Departments
• 3% from consumers over recent years

12. • TGA wants to ensure companies have adequate PV systems in place to ensure
medications available to Australian consumers are safe and effective - RMP
• Routine risk minimisation activities include:
• Product information
• Consumer Medicines Information
• Directions for use document
• The labelling
• The pack size and design
• The legal (prescription) status of the product
Additional risk minimisation activities include:
• Education programs for patients
• Health care professional education programs
• Dear health care professional letters
• Controlled access programme

13. • Routine pharmacovigilance plan includes:
• Collection, follow-up and reporting of adverse events
• Analysis of data and reporting in Periodic Safety Update Reports (PSURs)
• Additional pharmacovigilance includes:
• Clinical trials – limited information, not always representative of the real world usage
due to inclusion and exclusion criteria, potential risks identified but not fully
characterized, mossing information in certain population groups – children, pregnant
women and the elderly
• Post-authorisation safety studies
• Drug utilisation studies
• Patient registries
• Physician surveys
• Prescription event monitoring
Expert medical review of all individual reports is undertaken by staff with clinical
and diagnostic skills which helps to ensure high-quality data

14. CLINICAL PERSPECTIVES IN DRUG SAFETY AND
ADVERSE DRUG REACTIONS
• Underreporting of ADRs (spontaneous reporting, false casualty, workload)
• Quality of spontaneous reporting
• Proper evaluation of drug safety signals
• Inadequate knowledge and attitudes among doctors
• Initiatives to increase reporting
• Validity and reliability of consumer reporting
Reporting of suspected adverse reactions by health professionals to the ADRAC has generated
a number of important signals, helped to define the nature of the adverse reaction in questions
and some of the reporting doctors have been able to assist in further research
Promoting the concept that serious and unexpected adverse reactions should be reported
emphasizes the importance of drug safety issues, helps to detect reactions that might
otherwise go unrecorded

15. • Sponsors/Manufacturers must ensure pharmacovigilance system is in place
• Spontaneous adverse event reporting is voluntary, sponsor ADR reporting is
madatory
• Domestic reports, SUAs and expected ADRS must be reported to ADRAC in 15
days upon receipt of report
• Domestic clinical trial cases must be reported within 7 days for fatal/life
threatening. All other SAEs and SUAs within 15 days
• Special access scheme, authorized prescriber mechanism, and use of unapproved
products through personal importation are also reportable to ADRAC
• PSURs (Periodic Update Safety Reports) are submitted annually for the first 3
years after the date of approval letter (1st submitted not more than 15 months from
approval, subsequent reports submitted at least annually from the date of the first
submitted report)
ADR reporting

16. ADR REPORTING
• Consumers: Adverse Medicine Events Line
• Health professional:
• Reports to OMSM
• Submit a report to the Australian Adverse Drug Reaction Reporting
System using ADRAC ”Blue-Card” Adverse Reaction Reporting form
• Report directly to the MIMS Online
• Report via email, fax or mail using the National Adverse Events
Following Immunisation (AEFI) reporting form

17. ADVERSE EVENT REPORTING STATISTICS IN 2014
Fig: Origin of medicine and vaccine adverse events received by the TGA (2010-14)

18. Office of Medicines Safety
Monitoring (OMSM)
receives ADR reports
Australian Drug Evaluation
Committee (ADEC)Prescription medicines

Vaccines
OTC
Complementary medicine

 Adverse Drug Reactions
Committee (ADRAC)
evaluates the ADR reports
https://www.ebs.tga.gov.au/ebs/ADRS/ADRSRepo.nsf?OpenDatabase
Adverse Drug Reaction Reporting System
(database)
Cases received by ADRAC undergo
medical review, new safety
information is circulated to health
professionals via Australian ADRAC
Bulletin

19. ADR REPORTING
Medicine and
vaccine adverse
event reports that
the TGA receives
are entered into the
Australian Adverse
Drug Reaction
Reporting System
(ADRS).
Medical device
incident reports are
recorded in the
Incident Reporting
and Investigation
Scheme (IRIS)
database.
Within 2 working days
Send Letter of
Acknowledgement to
reporter
Report is given an unique
ID number
Receive adverse event
complaint
Information is transferred to
publicly accessible and
searchable Database of
Adverse Event Notifications
3 months from ADRS entry
Reports are forwarded to the Uppsala
Monitoring Centre in Sweden, which
administers the World Health
Organization Collaborating Centre for
International Drug Monitoring. This
global database (VigiBase) began in
1968 as a pilot program involving 10
nations, including Australia, and now
receives reports from more than 80
nations.

20. EDUCATION AND AWARENESS
• Initiatives taken by TGA and NPS MEdicineWise
• Two interactive online learning modules called ‘Safety through Reporting’
(Dec 2014)
• Objective: To increase health professional existing knowledge
around reporting adverse events associated with therapeutic
products
• Key features:
• The importance of reporting adverse events
• Sharing the responsibility of reporting
• How to build reporting into practice
• What happens to reports once they are submitted to the TGA

21. CONCLUSION
• Rapport with healthcare professionals and a reporting mindset have been
built over 40 years
• Important information regarding adverse drug reactions to drugs provide a
sound foundation for regulatory and educational activities, as well as
valuable resource for research.

22. REFERENCES
• www.tga.gov.au/presentatiion-pharmacovigilance-forum
• www.medscape.com
• http://www.tga.gov.au
• http://www.pharmoutsourcing.com/Featured-Articles/37484-Pharmacovigilance-in-
Australia-and-New-Zealand/
• http://www.who.int/medicines/areas/quality_safety/safety_efficacy/National_PV_Centres_
Map/en/
• Pharmacovigilance in Australia the Past, Present and Future, PPT Presentation, Dr.
Rohan Hammett

23. THANK YOU