Table 6: Sponsor’s summary of ongoing safety concerns Summary of ongoing safety concerns Important identified risks Hypoglycaemia Medication errors (insulin mix ups) Injection site reactions Hypersensitivity reactions Important potential risks Malignancies Antigenicity Medication error (inappropriate dose injected, following needle blocked in absence of compliance with instructions for use) Missing information Use in pregnancy (U300 only) Use in paediatric population (U300 only) Comment: The ongoing safety concerns differ from those previously accepted for Lantus as follows: The addition of the important potential risk: error ‘Medication (inappropriate dose injected, following needle blocked in absence of compliance with instructions for use)’. The addition of the missing information: in paediatric population ‘Use (U300 only)’, to reflect the lack of paediatric data for the higher concentration formulation and to capture any such off label use. Specifying the missing information: in pregnancy’ is applicable ‘Use only to the U300 presentation to reflect the significant exposure of pregnant women to the marketed U100 dosage form and the limited use in pregnancy during clinical development with U300. Notwithstanding the evaluation of the nonclinical and clinical aspects of the Safety Specification, the above summary of the Ongoing Safety Concerns is considered acceptable. Reconciliation of issues outlined in the RMP report Table 7 summarises the first round evaluation of the RMP, the sponsor’s responses to issues raised by the RMP evaluator and the evaluation of the sponsor’s responses. Table 7: Reconciliation of issues outlined in the RMP report Recommendation in RMP Sponsor’s response RMP evaluator’s comment evaluation report 1. The sponsor should provide The sponsor has provided copies This is acceptable copies of the targeted structured of the targeted structured forms as forms used to follow up ICSRs specified and stated: note “Please related to the important identified there are no proposed targeted risk: errors (insulin structured forms to follow up ‘Medication mix ups)’ and to the important ICSRs related to the 3 new potential risk: error important potential risks ‘Medication (inappropriate dose injected, incorporated in the updated
Table 6: Sponsor’s summary of ongoing safety concerns Summary of ongoing safety concerns Important identified risks Hypoglycaemia Medication errors (insulin mix ups) Injection site reactions Hypersensitivity reactions Important potential risks Malignancies Antigenicity Medication error (inappropriate dose injected, following needle blocked in absence of compliance with instructions for use) Missing information Use in pregnancy (U300 only) Use in paediatric population (U300 only) Comment: The ongoing safety concerns differ from those previously accepted for Lantus as follows: The addition of the important potential risk: ‘Medication error (inappropriate dose injected, following needle blocked in absence of compliance with instructions for use)’. The addition of the missing information: ‘Use in paediatric population (U300 only)’, to reflect the lack of paediatric data for the higher concentration formulation and to capture any such off label use. Specifying the missing information: ‘Use in pregnancy’ is applicable only to the U300 presentation to reflect the significant exposure of pregnant women to the marketed U100 dosage form and the limited use in pregnancy during clinical development with U300. Notwithstanding the evaluation of the nonclinical and clinical aspects of the Safety Specification, the above summary of the Ongoing Safety Concerns is considered acceptable. Reconciliation of issues outlined in the RMP report Table 7 summarises the first round evaluation of the RMP, the sponsor’s responses to issues raised by the RMP evaluator and the evaluation of the sponsor’s responses. Table 7: Reconciliation of issues outlined in the RMP report Recommendation in RMP evaluation report Sponsor’s response RMP evaluator’s comment 1. The sponsor should provide copies of the targeted structured forms used to follow up ICSRs related to the important identified risk: ‘Medication errors (insulin mix ups)’ and to the important potential risk: ‘Medication error (inappropriate dose injected, The sponsor has provided copies of the targeted structured forms as specified and stated: “Please note there are no proposed targeted structured forms to follow up ICSRs related to the 3 new important potential risks incorporated in the updated This is acceptable
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