Table 2. Sponsor’s proposed routine and additional pharmacovigilance activities type Objectives Safety concerns addressed Status (planned, started) Date for submission of reports1 Routine ISCRs, PSURs/DSURs monitoring safety profile, safety signal detection and evaluation To collect all AE reports and monitor these, along with other sources of safety information to detect and changes in the safety profile over time All Planned To be implemented when the QIV receives MAA PSUR to be submitted as per regulatory requirement Signal detection activities will be conducted as defined in the sponsor signal detection SOP Postmarketing surveillance of the QIV exposure in pregnancy and pregnancy outcomes To collect the missing information of exposure of the QIV in pregnant women Exposure and safety of the QIV in pregnancy (missing information) To be planned and implemented when MAA is obtained for the QIV ASR from pregnancy safety surveillance and final safety report from the pregnancy safety surveillance ISCR = Individual Case Safety Report; PSUR = Periodic Safety Update Report; DSUR = Developmental Safety Update Report; MAA = Marketing Authorisation Approval; SOP = Standard Operating Procedure; ASR = Annual Safety Report. 1) Refers to interim or reports (planned or actual). Risk minimisation activities Only routine risk minimisation activities are proposed for all safety concerns in Australia. Reconciliation of issues outlined in the RMP report 3 summarises the TGA’s first round evaluation of the RMP, the sponsor’s responses to issues raised by TGA the in the evaluation of the sponsor’s responses. Table 3. Reconciliation of issues outlined in the RMP report. Recommendation in RMP evaluation report Sponsor’s response (or summary of the response) RMP evaluator’s comment Safety considerations may be raised by the nonclinical and clinical evaluators through consolidated TGA questions for the sponsor and/or the The nonclinical evaluation report suggests addition of ‘No embryofetal development study has been conducted with Afluria Quad’ to the precautions section of the PI. We accept TGA’s recommendation and have added this statement to the PI provided with this response. The clinical evaluation report provided no recommendations related to safety. The sponsor’s response has been noted.
clinical evaluation report. It is important to ensure that the information provided in response to these includes a consideration of the relevance for the RMP, and any specific information needed to address this issue in the RMP. For any safety considerations so raised, please provide information that is relevant and necessary to address the issue in the RMP. It is expected that any subsequent versions of the RMP/ASA or RMP/ASA updates for the Afluria Quad contain relevant safety information from the RMP for the Fluvax TIV. The same applies to the proposed PI and CMI documents. The sponsor commit to providing an updated RMP and ASA with relevant information from the RMP for the trivalent vaccine. The updated RMP and ASA will be submitted to the TGA after the conclusion of evaluation. This is considered acceptable in the context of this application. Due to its importance in this case, the sponsor should provide add ‘Off-label use’ as a separate Important Potential Risk to be addressed with additional risk minimisation activities. The sponsor commits to include off-label use in children 5 to 17 years of age as an important Potential Risk in an updated RMP. In addition, the sponsor commits to providing additional risk minimisation measures and a proposal to evaluate the effectiveness of such measure/s (as outlined in the sponsor’s response to questions Q.16 and Q.17) until such time that an authorised indication of Afluria Quad for use in this age group has been obtained. The sponsor believes that the proposed additional risk minimisation measures in children under 18 years are sufficient and will be continued to ensure the vaccine is not used in this age group. This is considered acceptable in the context of this application.
provide a summary of the post-market experience with device failure with that device and its effects (for example underdosing). Australia, post-market experience with device failure is not relevant to the pre-filled syringe presentation. Assuming, the PharmaJet Stratis jet injector device is used, the sponsor should provide a summary of the post-market experience with device failure with that device and its effects (for example underdosing). Only the pre-filled syringe presentation is will be registered and used in Australia. The sponsor’s response has been noted. The sponsor should state how they propose to address the issue of confusion between the Fluvax TIV and the Afluria Quad and their indications. Additional risk minimisation activities would be needed to mitigate off-label use. As stated within an influenza season, only one vaccine, either Fluvax TIV or Afluria Quad will be supplied to the market by the sponsor. Appropriate educational materials will be provided to educate Australian health professionals about the indications of Afluria Quad vaccine. These materials outlined in Q.17 will be developed following registration and prior to the anticipated launch of the vaccine in the Australian market. Once prepared, these materials can be made available to the TGA. The sponsor’s response has been noted. It is furthermore noted that the sponsor is already proposing an extension of indication that would align the current indication of the TIV with the overall proposed indication of Afluria Quad. If approval for this extension of indication were given before supply of the Afluria Quad under the currently proposed indication, the age ranges would be aligned. However, if the application for
consideration by the Delegate. In the ‘Precautions’ section, the PI should contain a statement with regard to giving the vaccine to patients who had syndrome in the last 6 weeks. The statement ‘If Guillain-Barré syndrome has occurred within 6 weeks of previous influenza vaccination, the decision to give Afluria Quad vaccine should be based on careful consideration of the potential benefits and risks.’ has been added in the updated PI. This is considered acceptable in the context of this application for RMP purposes pending consideration by the Delegate. In the ‘Interactions’ section the PI should contain a statement that if Fluvax vaccine were to be administered concurrently with other vaccines, separate syringes and a separate arm should be used. This statement is currently listed in the Dosage and Administration section of the PI which the sponsor believes to be the most appropriate placement of this statement as it relates to administration of the vaccine not an interaction. This is considered acceptable in the context of this application for RMP purposes pending consideration by the Delegate. In the ‘Contraindications’ section, the PI should contain ‘patients younger than 18 years of age’ as a contraindication. The statement ‘Afluria Quad is contraindicated in children < 18 because the safety and efficacy in this age group has not been established’ has been added in the updated PI. This is considered acceptable in the context of this application for RMP purposes pending consideration by the Delegate. In the ‘Dosage and Administration’ section, the PI should include a statement that administration should occur by a health care practitioner in an appropriate setting with an appropriate observation period. The statement ‘Afluria Quad vaccine should be administered by a health care practitioner in an appropriate setting with an appropriate observation period.’ has been added in the updated PI. This is considered acceptable in the context of this application for RMP purposes pending consideration by the Delegate.