ACSOV meeting statement, Meeting 9, 23 October 2015
Advisory Committee on the Safety of Vaccines
Role of the Advisory Committee on the Safety of Vaccines (ACSOV) in the TGA's regulatory decision making process
The ACSOV is a statutory advisory committee established by the Therapeutic Goods Regulations 1990.
The TGA currently has ten statutory advisory committees from which it can obtain independent expert advice on specific scientific and technical matters to aid the TGA's regulatory decision making and other regulatory processes.
The ACSOV provides advice to the TGA and the Office of Health Protection (OHP) on, amongst other things, matters relating to the safety, risk assessment and risk management of vaccines supplied in Australia.
How this statement should be read
The advice provided by the ACSOV is an important element in the undertaking of the regulatory functions of the TGA. However, it forms only one part of the total body of information that is available to, for instance, a TGA delegate making a regulatory decision under the Therapeutic Goods Act 1989 ('the Act'). Therefore, while appropriate consideration will be given to such advice, it is important to note that neither the TGA nor a TGA delegate is obliged to follow it.
It should also be noted that details of the committee's advice may not become publicly available for some time after the committee has provided that advice. The purpose of this Meeting Statement is to describe in general terms the matters considered by the committee at each meeting and for it to be available as soon as reasonably practical after the relevant meeting.
Additionally, following publication of this statement, it is most likely that further work will be undertaken by the TGA to investigate, monitor and/or evaluate the vaccines considered by the ACSOV; and this will continue for some time into the future. It is therefore possible that further information about the vaccines will become publicly available at a later time and this will be pursuant to a regulatory decision under the Act being made and following further consultation with the vaccine's sponsor and/or manufacturer.
Overview of the safety reviews and therapeutic goods referred for advice
The TGA continually monitors therapeutic goods supplied in Australia to ensure their ongoing safety, efficacy and quality. As part of this process, the TGA routinely undertakes safety reviews of therapeutic goods.
At this meeting, the committee's advice was sought on the following safety reviews and adverse event investigations.
Update on influenza vaccines and increased immune system AEFI reporting
At ACSOV 8, the committee was advised that the TGA had begun an investigation into an observed increase in reports, compared to previous years, of Immune System Disorders (ISD) following the administration of the 2015 influenza vaccines. As urgent program or regulatory action was not indicated, the TGA advised that it would undertake further analysis with more complete data and provide ACSOV with the results.
At the current meeting, the committee noted that continued TGA investigation has confirmed an increase in the numbers of ISD adverse events following immunisation (AEFI) reported to the TGA in 2015, compared to the number of cases reported across the previous four years. There was also an increase in the proportion of ISD cases to total AEFI case reports. There was no increase in the total number of influenza vaccine AEFI case reports in 2015.
The TGA analysis of five years of data focused on five allergic AEFIs (anaphylactic reaction, angioedema, asthma/ bronchospasm, urticaria and hypersensitivity), selected as being potentially the most serious adverse events. There have been no unusual features of the cases reported this year and the time to onset has been as expected for such reactions.
The TGA considered that the results of its analysis should be interpreted with caution owing to low numbers and wide variability across the data examined.
The committee also noted separate collection and analysis of signals of immune system AEFI by other agencies. Victoria's SAEFVIC (Surveillance of Adverse Events Following Vaccination In the Community) concluded, based on data to 6 October 2015:
The early notification of a 'possible signal' of an allergy-related adverse event reporting following TIV [trivalent influenza vaccine] was timely and justified. Further monitoring conducted through the season provides an observed, non‐statistical increase in generalized allergy-related AEFI, with no correlation with any specific vaccine brand or allergic symptom and did not indicate severe clinical outcomes above historical AEFI reporting parameters.
New Zealand's Centre for Adverse Reactions Monitoring commented, based on data to 30 June 2015:
The 2015 seasonal trivalent influenza vaccination program does appear to have a level of hypersensitivity adverse event reports that is at the extreme of the levels seen in the last 4 to 5 years.
The committee also reviewed pre-publication1 AusVaxSafety cumulative data to 31 August 2015 on children under 5 years of age which had disclosed no safety signal and unpublished data on seasonality of laboratory detected respiratory pathogens.
Having considered these latest analyses, the committee provided further comment on the data and suggested additional analyses that could be undertaken with the existing data. The committee also suggested that interrogation of other datasets would be useful. This could include the Western Australian Vaccine Safety Surveillance System (WAVSS) database which follows seasonal influenza vaccination among healthcare workers, and Vigibase2.
Overall, the data suggested an increase in allergy related AEFI, but the signal was not strong and this did not have any significant programmatic or clinical implications. The committee agreed it was reassuring that similar conclusions had been independently reached by the TGA and SAEFVIC although each used a different method for coding the reported adverse events.
Risk Management Plans (RMP)
A Risk Management Plan (RMP) is a set of pharmacovigilance activities and interventions designed to identify, characterise and manage risks relating to a medicine or a vaccine. At this meeting, the committee's advice was sought on one RMP for a medicine with proposed indications relating to neoplastic disorders.
The committee was asked to provide advice on matters including the adequacy of the proposed risk minimisation plan intended to mitigate the risks of the medicine. The committee's advice will shortly be provided to the TGA for consideration as part of the TGA's regulatory decision making processes.
Following complete assessment of the application, information on the RMP evaluation will be included in the Australian Public Assessment Reports (AusPAR), which is published on the TGA website once it is finalised.
Immunisation Program advice
No specific program advice was sought at this meeting.
Meeting statements are made publicly available after each meeting.
- Since the ACSOV meeting was held, this data has now been published and is available at <http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=21286>
- VigiBase is the name of the World Health Organisation's (WHO) global database of Individual Safety Case Reports (ICSR) submitted from member countries in the WHO Programme for International Drug Monitoring.