About this guideline
Overseas effective date: 12 Dec 2017
Categories: Biological medicines | Drug substance | Vaccines (drug substance)
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TGA annotations
Proposed TGA annotations
- Concerning 5.1.1. Requirements for authorisation.
Proposed annotation: For registration of a new seasonal influenza vaccine in Australia the TGA would generally require that the new vaccine demonstrates vaccine efficacy in a placebo-controlled trial, or non-inferior immunogenicity in comparative clinical studies against an influenza vaccine registered in Australia. If the studies for the new influenza vaccine are not prophylactic efficacy versus placebo or non-inferior immunogenicity against a registered influenza vaccine, it is likely that TGA will require the immunogenicity of the new vaccine versus a concurrent unvaccinated group to fulfil the criteria specified in the current relevant US FDA Guidance for Industry: Clinical Data Needed to Support the Licensure of Seasonal Inactivated Influenza Vaccines (15 September 2014 or more recent update.)
- Concerning 7.2 Post-authorisation pharmacovigilance requirements for seasonal influenza vaccines. This section refers to the addendum document Guidance on enhanced safety surveillance for seasonal influenza vaccines in the EU (EMA/PRAC/222346/2014).
The TGA has adopted the EMA Interim guidance on enhanced safety surveillance for seasonal influenza vaccines in the EU (EMA/PRAC/222346/2014) with the exception of section 3. Data reporting and submission requirements for vaccines for which sponsors are conducting enhanced safety surveillance will be determined on a case-by-case basis.
All applications in Australia to register new seasonal influenza vaccines must include a risk management plan, which should include a plan for enhanced safety surveillance as described in Section 2 of the Interim guidance on enhanced safety surveillance for seasonal influenza vaccines in the EU (EMA/PRAC/222346/2014).
The need for different enhanced surveillance options will be evaluated on a case-by-case basis by the TGA. However, if a seasonal influenza vaccine is included in a suitable national safety surveillance program in Australia (e.g. AusVaxSafety), there would usually be no requirement for a sponsor to also conduct enhanced safety surveillance.
If relevant product-specific Northern Hemisphere safety data are available and do not reveal any identified safety signals following confirmed use of the product, the sponsor may justify the relevance and validity of the Northern Hemisphere experience with the product and propose not to undertake enhanced safety surveillance.
Before each Southern Hemisphere influenza immunisation season, sponsors should ensure that the pharmacovigilance plans for their seasonal influenza vaccines remain adequate to rapidly detect any increase in the frequency and/or severity of expected reactogenicity (local, systemic or allergic reactions). Effective monitoring is especially important when a seasonal strain change introduces a strain in the Southern Hemisphere prior to use in the Northern Hemisphere.
In determining the need to alter the pharmacovigilance plan of the risk management plan, the sponsor should consider:
- whether there has been any change to the vaccine's indications or the population in which it will be used (for example, a change in the approved age range),
- whether there will be a strain change or other change to the vaccine that could result in a change in reactogenicity, and
- if the vaccine will be included in national safety surveillance programs in Australia.
If there has been a strain change for a vaccine that will not be included in a national safety surveillance program in Australia and the sponsor proposes not to perform enhanced safety surveillance because of the availability of relevant product-specific safety data from the Northern Hemisphere, then this strategy should be discussed with the TGA as soon as the safety data from the Northern Hemisphere are available.
If a change to the pharmacovigilance plan is required, the sponsor should submit an updated risk management plan to the TGA with the application for seasonal strain variation.
If the pharmacovigilance plan remains adequate for the new influenza season, and there are no other significant changes to the risk management plan, then there is no requirement to submit an annual risk management plan update to the TGA.
Sponsors are reminded of their obligations for reporting significant safety issues in accordance with the Australian requirements and recommendations for pharmacovigilance responsibilities of sponsors of medicines. Significant safety issues arising from safety data available from prior use of the vaccine and/or enhanced surveillance activities in the Northern Hemisphere should be promptly reported to the TGA.
A sponsor should give support to the conduct of Southern Hemisphere effectiveness studies, such as case test-negative studies, especially when a seasonal strain change introduces a strain in the Southern Hemisphere prior to use in the Northern Hemisphere.
- Concerning 7.4 Post-authorisation pharmacovigilance requirements for Pandemic influenza vaccines.
The second dot-point is amended by the inclusion of an introductory sentence:
- If the pandemic influenza virus is of a HN subtype for which nonclinical and clinical data have not been included in the Core Pandemic Dossier, it is highly desirable that nonclinical and clinical data obtained from studies with the pandemic HN subtype be included in the pandemic variation dossier.
For more information see International scientific guidelines adopted in Australia.
Where 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 medicines by the TGA.