Throbocytopenia Important potential Aterial Thrombotic Events (ATEs) Malignant neoplasms (in paediatric patients 6 to 12 years old) Off label use Important missing information Pregnancy outcomes Pharmacovigilance plan The sponsor proposes routine pharmacovigilance activities to monitor all the specified ongoing safety concerns, including the use of a targeted follow up questionnaire/checklist for the important identified risks: ‘Anaphylaxis/anaphylactoid reactions’ and ‘Malignant neoplasms in adults and adolescents ≥ 12 years of age’ and the important potential risk: ‘Arterial Thromboembolic Events (ATEs)’. Risk minimisation activities The sponsor proposes that routine risk minimisation activities for all the specified ongoing safety concerns are sufficient. Reconciliation of issues outlined in the RMP report Table 9 summarises the PMSB’s first round evaluation of the RMP, the sponsor’s responses to issues raised by the PSMB and the PSMB’s evaluation of the sponsor’s responses. Table 9. Reconciliation of issues outlined in the RMP report Recommendation in RMP evaluation report Sponsor’s response PSMB evaluator’s comment 1. Safety considerations may be raised by the clinical evaluator through the TGA’s consolidated request for information and/or the CER respectively. It is important to ensure that the information provided in response to these include 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, the sponsor should provide information that is relevant and The sponsor makes no specific response to this recommendation, but states: ‘The ASA, has been updated to incorporate the RMP evaluator’s recommendations.’ The clinical evaluator did not raise any additional safety considerations. trial
necessary to address the issue in the RMP. 2. The ongoing studies are not considered to be part of the planned clinical studies in the pharmacovigilance plan. Therefore the related study protocols have not been reviewed. Nevertheless these studies will either generate safety data that will simply support the known safety profile of the medicine or generate data that will provoke applications to amend the Australian registration details. Consequently the table in Section 5.2.1 of the ASA should be amended to state the anticipated dates for their submission in Australia, rather than in the EU. The sponsor makes no specific response to this recommendation, but states: ‘The ASA, has been updated to incorporate the RMP evaluator’s recommendations.’ However, the sponsor has only amended this table by stating for each study: ‘No submission planned to TGA. Final report available upon request.’ This response is considered unsatisfactory, as it is expected that submission of studies in Australia would be closely aligned to the planned date for submission of the final report in the EU whether it is referred to in a Product Safety Update Report (PSUR) or submitted in an application to amend the Australian registration details. Therefore this issue remains outstanding and should be adequately addressed, including any updating of the anticipated dates, before this application is approved. 3. The sponsor’s conclusion that routine risk minimisation activities for all the specified ongoing safety concerns are sufficient remains similar to what was previously accepted for Xolair and at this time continues to be acceptable. The sponsor makes no specific response to this recommendation. n/a 4. At this time the sponsor’s handling of the potential for medication errors with Xolair using routine pharmacovigilance and risk minimisation activities continues to remain acceptable. The sponsor makes no specific response to this recommendation. n/a 5. As per the (RMP) Questions and Answers (Version 1.3, October The sponsor no specific response to this recommendation, but No tabular comparison identifying and providing reasons for