this additional EU requirement. 11. The sponsor should In response to the TGA’s The response has been provide a table summarising requested changes, please noted. However, this the safety specification, refer to the updated ASA table should be amended pharmacovigilance plan and provided in this response. to include the potential planned risk minimization risk of of efficacy’. ‘lack measures in Australian context in the ASA. Wording pertaining to important safety concerns in the proposed Australian PI and CMI should be included in the table. 12. The sponsor should amend As discussed in the Question This is considered the ASA to describe 4.1, bradycardia and pyrexia acceptable. and are not considered as ‘bradycardia’ ‘pyrexia related effects’ as identified identified risk on the risk. Furthermore, to align the review by OE. classification of the ongoing Further, the risks of safety concerns with the and food and ‘unknown EURMP, the ASA should be drug interactions’ and amended to classify ‘unknown on pregnancy and ‘effects food and drug interactions’ foetal outcome’ have been and effects on pregnancy and included within the RMP foetal outcome’ as missing (Section 2.4.4) and also information. within the updated ASA. These documents have been provided in the response. 13. The sponsor describes The sponsor confirms that This is considered pharmacovigilance pharmacovigilance acceptable. ‘routine ‘routine activities’ in section 3.1.1 and activities’ and of the ‘review of the safety safety information derived ‘review information derived through through the Carbaglu the Carbaglu surveillance surveillance protocol’ have protocol’ in section 3.1.2 of the been included within the ASA as planned actions in the pharmacovigilance plan risk minimization plan. These section of the ASA rather activities constitute than the risk minimization pharmacovigilance activities section. and therefore, are not considered part of the risk minimisation plan. 14. Recommendations for The sponsor can confirm Regarding the potential amendments of the PI/CMI. amendments recommended risk of Rash, the sponsor within the TGA’s evaluation states in the EU-RMP report have been made to will be added in the ‘Rash the proposed Australian PI Summary of Product and CMI. Copies of the Characteristics (SmPC): frequency uncommon’.
this additional EU requirement. 11. The sponsor should provide a table summarising the safety specification, pharmacovigilance plan and planned risk minimization measures in Australian context in the ASA. Wording pertaining to important safety concerns in the proposed Australian PI and CMI should be included in the table. In response to the TGA’s requested changes, please refer to the updated ASA provided in this response. The response has been noted. However, this table should be amended to include the potential risk of ‘lack of efficacy’. 12. The sponsor should amend the ASA to describe ‘bradycardia’ and ‘pyrexia related effects’ as identified risk. Furthermore, to align the classification of the ongoing safety concerns with the EURMP, the ASA should be amended to classify ‘unknown food and drug interactions’ and effects on pregnancy and foetal outcome’ as missing information. As discussed in the Question 4.1, bradycardia and pyrexia are not considered as identified risk on the review by OE. Further, the risks of ‘unknown and food and drug interactions’ and ‘effects on pregnancy and foetal outcome’ have been included within the RMP (Section 2.4.4) and also within the updated ASA. These documents have been provided in the response. This is considered acceptable. 13. The sponsor describes ‘routine pharmacovigilance activities’ in section 3.1.1 and ‘review of the safety information derived through the Carbaglu surveillance protocol’ in section 3.1.2 of the ASA as planned actions in the risk minimization plan. These activities constitute pharmacovigilance activities and therefore, are not considered part of the risk minimisation plan. The sponsor confirms that ‘routine pharmacovigilance activities’ and ‘review of the safety information derived through the Carbaglu surveillance protocol’ have been included within the pharmacovigilance plan section of the ASA rather than the risk minimization section. This is considered acceptable. 14. Recommendations for amendments of the PI/CMI. The sponsor can confirm amendments recommended within the TGA’s evaluation report have been made to the proposed Australian PI and CMI. Copies of the Regarding the potential risk of Rash, the sponsor states in the EU-RMP ‘Rash will be added in the Summary of Product Characteristics (SmPC): frequency uncommon’.
auspar-carglumic-acid-150902.docx