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

Courtesy of Dr. Peivand Pirouzi

• 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%)

HEALTH CARE SYSTEM IN AUSTRALIA

http://www.aihw.gov.au/australias-health/2014/health-system/

• 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

• 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

• 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)

• 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

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.

• 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

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

• 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

• 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

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

• 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

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

ADVERSE EVENT REPORTING STATISTICS IN 2014

Fig: Origin of medicine and vaccine adverse events received by the TGA (2010-14)

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

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.

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

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.

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

THANK YOU