Drug safety in Australia is regulated via the Office of Medicines Safety Monitoring (OMSM) (synonymous with Adverse Drug Reaction Advisory Committee), a branch of the Therapeutic Goods Administration (TGA). In New Zealand, Medsafe is the regulatory agency responsible for overseeing drug safety/ pharmacovigilance activities. Both regulatory agencies’ mission is accomplished by applying a framework that ensures benefits in the use of therapeutic products while managing the potential risks. Both regulatory agencies have their own pharmacovigilance requirements and both agencies collaborate with other national monitoring centers and into the database of the WHO’s International Drug Monitoring Program.
For the purpose of this article, pharmacovigilance means the collection and submission of adverse experiences and other safety information related to drugs to the respective regulatory agencies of Australia and New Zealand.
Australia
Therapeutic Goods Act 1989 provides a national framework for the regulation of therapeutic goods in Australia to ensure quality, safety and efficacy of medicines.
The Therapeutic Goods Administration (TGA) is a unit of the Australian Government Department of Health and Ageing that is responsible to ensure the administration of the provisions of the legislation, Therapeutic Goods Act 1989. The TGA carries out assessment and monitoring activities to ensure that therapeutic goods available in the Australian market are of acceptable standard.
The TGA Office of Medicines Safety Monitoring receives reports of suspected adverse reactions to prescription medicines, vaccines, over-the-counter medicines and complementary medicines. All reports are reviewed by professional staff. Reports involving serious reactions or recently marketed drugs are reviewed by the Adverse Drug Reactions Committee (ADRAC). The Adverse Drug Reactions Committee (ADRAC) is a subcommittee of the Australian Drug Evaluation Committee (ADEC) which was formed in 1970 to advise TGA on the safety of medicines.
The Australian pharmacovigilance requirements have been implemented using the following 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.
It is expected that drug Sponsors/Manufacturers must ensure that an appropriate system of pharmacovigilance be in place in order to assume responsibilities and liability for its products on the market and to ensure that the appropriate action can be taken when necessary.
Spontaneous adverse event reporting is voluntary in Australia. Domestic reports, serious expected and unexpected received by sponsors/manufacturers from healthcare professionals, patients and consumers are to be reported to ADRAC in an expedited manner (15 days). Cases from worldwide literature and reports from post-registration studies are also reported to ADRAC within 15 days upon receipt of reports.
Domestic clinical trial cases are to be reported within 7 days for fatal/life-threatening serious unexpected adverse reactions and all other serious unexpected adverse reactions (SUA’s) within 15 days. Special access scheme, authorized prescriber mechanism and use of unapproved products through personal importation are also reportable to ADRAC.
PSURs (Periodic Safety Update Reports) are submitted annually for the first 3 years after the date of the approval letter. The first must be submitted no later than 15 calendar months after approval. Subsequent reports must be submitted at least annually from the date of the first submitted report.
Minimum reporting criteria for reporting of ADRs to ADRAC are:
- Identifiable patient
- Medicinal product
- Identifiable reporter
- Event
One of the features of the Australian pharmacovigilance system is the high proportions of direct reporting by health professionals using the ADRAC “Blue-Card.” Cases received by ADRAC are subjected to medical review and new safety information is circulated to the healthcare professionals via the Australian ADRAC Bulletin [1].
Recently, the TGA embarked on several initiatives [1]: Web-based electronic report form in Australia with reporting facility in GP software; dedicated pilot consumer reporting line; Risk Management Plans being introduced and Life cycle management of products. These initiatives are important for TGA to further fulfill its pharmacovigilance commitment to the Australian community.
Like all other regulators, the TGA are faced with challenges and here are some of these challenges [1]:
- Pharmacovigilance still largely limited to spontaneous reporting: Limitations include difficulties with adverse event recognition, underreporting, biases, estimation of population exposure, and report quality
- Data-mining potentials and pitfalls: No current guideline on standards for the use of these methods in routine pharmacovigilance
- Risk management: Ongoing “monitoring” and “fine-tuning” required to ensure value to public health
- Pharmacoepidemiology: Practice guidelines required for conduct of pharmacoepidemiology studies
- Global problems: global responses
New Zealand
New Zealand produces the highest rate of reporting adverse drug reactions in the world, both in terms of reports per 1000 doctors and reports per million population [2].
Pharmacovigilance responsibilities in New Zealand are overseen by the following groups:
Medsafe is the regulatory agency responsible for overseeing pharmacovigilance activities in New Zealand. The regulatory responsibility of Medsafe is to administer the Medicines Act 1981 and parts of the Misuse of Drugs Act 1975, and their accompanying Regulations [3].
CARM (Centre for Adverse Reactions Monitoring) processes all reports of adverse reactions and enters the information into its database.
MARC (Medicines Adverse Reactions Committee) is a ministerial advisory committee of general practitioners and medical specialists. MARC oversees the spontaneous adverse reaction reporting scheme and the IMMP (Intensive Medicines Monitoring Programme), reviews adverse reaction data published in the medical literature and advises the Minister and Medsafe on issues relating to the safety of medicines, including information to be disseminated to prescribers and pharmacists.
The New Zealand pharmacovigilance requirements have been implemented using the following Guidelines:
- Medicines Act 1981
- New Zealand Regulatory Guidelines for Medicines Volume 1, Fifth Edition
New Zealand has an established and effective pharmacovigilance system for post-marketing surveillance of medicine use. This includes the spontaneous adverse reactions reporting scheme and an Intensive Medicines Monitoring Programme.
Reporting of Spontaneous Cases is voluntary in New Zealand: Sponsors/manufacturers are responsible to report adverse reactions occurring within New Zealand that are either serious or unexpected (unlisted), and to report these to the Centre for Adverse Reactions Monitoring (CARM).
Reporting of Clinical Trial Cases: Sponsors/manufacturers are responsible to report Fatal/Life- threatening, unexpected adverse reactions occurring within New Zealand within 7 calendar days. All other SAEs including Serious Unexpected adverse reactions (SUAs) are to be reported within 15 calendar days.
PSURs (Periodic Safety Update Reports): Sponsors/manufacturers are required to submit only upon request by Medsafe or if a product(s) is included in a submission to Medsafe on a safety issue(s).
Intensive Medicines Monitoring Program (IMMP): Practitioners are requested to report to CARM all adverse clinical events occurring in patients receiving IMMP medicines (whether or not they are thought to be causally related to the medicine concerned). Pharmacists are requested to send in records of all dispensing of these medicines.
All reports received by CARM are entered on the CARM database. These reports are evaluated to assess the causal relationship between the drugs and reported reactions.
Conclusion
Compliance with the TGA and Medsafe requirements for pharmacovigilance reporting is essential, regulatory action is taken for non-compliant sponsors/manufacturers. Regulatory action will depend on the potential impact on public health safety.
References
- Dr Leonie Hunt, Recent Trends in Pharmacovigilance in Australia, IFPMA 2008
- New Zealand Pharmacovigilance Centre: CARM. 2004
- New Zealand Regulatory Guidelines for Medicines. Volume 1, Fifth Edition, Oct 2001
- Australian Guideline for Pharmacovigilance Responsibilities of Sponsors of Registered Medicines Regulated by Drug Safety & Evaluation Branch ( July 2003 , amended 31 May 2005)
- Ronald Mann, Elizabeth Andrews. Pharmacovigilance, 2nd Edition 2007.
Dr. Arlene Amor currently serves as Director of Caerus Consulting, an Australia-based CRO. She is a recognized expert in Pharmacovigilance in Asia Pacific. Prior to joining Caerus, Dr. Amor was the Regional Head Asia-Pacific for Benefit Risk Management (BRM), division of Johnson & Johnson. Her role in the Asia-Pacific region was focused on the development and support of pharmacovigilance activities in J&J operating companies in Asia Pacific. Dr. Amor has also been involved as a speaker and adviser on many drug safety issues for various Regulatory Agencies within Asia Pacific. She has also been involved with a number of initiatives to promote and develop pharmacovigilance in the region.
Dr. Amor has over 19 years of experience in the pharmaceutical industry. She is trained as a physician in the Philippines. She started her career in Australia in 1990 with the Devices Branch of the Therapeutics Goods Administration (TGA: Australian health authority) where she worked for several years as a Technical Reviewer. She entered the pharmaceutical industry and held various senior management positions which included Director of Clinical Operations Asia-Pacific (Omnicare), Associate Medical Director/Safety Officer (Upjohn/Pharmacia) and as Medical Director (Solvay).
This article was printed in the March/April 2010 issue of Pharmaceutical Outsourcing, Volume 11, Issue 2. Copyright rests with the publisher. For more information about Pharmaceutical Outsourcing and to read similar articles, visit www.pharmoutsourcing.com and subscribe for free.