to 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 necessary to address the issue in the RMP. Recommendation 2: The DLP of the submitted RMP is 10 October 2013. It is recommended that the sponsor submits a more up to date version of the EU-RMP with their response to TGA questions. A copy of the current EU-RMP, Version 1.2 dated 13 August 2015 is provided, together with an updated ASA. It is noted that the DLP remains the same as the previous version. Recommendation 3: Amendments to the table of ongoing safety concerns as detailed in the RMP evaluation report. In the RMP evaluation report the evaluator includes the following comment: 1) Currently no long term (> 12 months) safety data is available and therefore, this should be added as missing information. 2) Hypersensitivity/ Immunogenicity should be added as a potential risk. The updated European RMP (Version 1.2) provided includes long term safety as ‘Missing Information’, and Immunogenicity as an ‘Important Potential Risk’, in line with current safety knowledge. This is also reflected in the ASA. This is acceptable from an RMP perspective. Recommendation 4: In a of the EU-RMP (Exclusion Criteria That are Not Proposed to Remain as Contraindications) the sponsor describes exclusion criteria for the clinical development program where no data is available. It is noted that many of these criteria are of relevance to clinical practice, especially as the indication sought is not a first line indication and therefore, patients are expected to have received prior treatment. The sponsor should elaborate on all criteria described in this table, and provide detailed justification as to why it would be considered The sponsor has provided the requested information and justification. It is noted that the most recent RMP now includes several of these criteria as missing information. This is acceptable from an RMP perspective.
new information will be communicated appropriately. Recommendation 7: ACSOM advice will be sought regarding the appropriateness of the currently proposed pharmacovigilance plan. The sponsor notes that ACSOM advice will be sought regarding the proposed pharmacovigilance plan. The Delegate is advised that the ACSOM advice has been incorporated into the final RMP Recommendation 8: It is recommended that the sponsor produces a preparation/dosing guide or chart which may aid to mitigate the risk of medication errors. The sponsor will be implementing additional risk minimisation measures for the safety concerns of neurologic events, medication errors and cytokine release syndrome as outlined in Response to Recommendations 9 and 10 (and the revised ASA to the EU RMP Version 1.2). This includes provision of individual educational materials directed to pharmacists, physicians, nurses and patients. Each of these materials includes information aimed specifically at raising awareness and minimising the risk of medication errors. In particular, the preparation guide for pharmacists contains detailed information regarding the reconstitution and preparation procedures for blinatumomab. These brochures are in line with those prepared for the EU, with the exception that the Australian pharmacist brochure has instructions on preparing cassettes in addition to IV bags. In addition to educational materials, the sponsor has also planned an observational patient registry study (Protocol 20150136; Annex 6 of EU RMP v1.2) in Europe to further characterise the safety profile of blinatumomab in routine clinical practice. The proposed Pharmacist’s guide has been reviewed for general content (Note, the evaluator has not reviewed individual calculations for accuracy). The guide should also include the instruction that ‘for comprehensive preparation instructions, please refer to the Blincyto PI’.
The sponsor considers that these measures, in addition to the gratuitous preparation and dosing instructions included in the PI, will provide sufficient guidance to healthcare professionals to mitigate the risk of medication errors occurring. The proposed risk minimisation activities include a Pharmacist Preparation Guide, Physician Educational Brochure, Nurse Educational Brochure and Patient (Caregiver) Educational Brochure. Recommendation 9: It is recommended that the sponsor amends the proposed Dear Health Care Professional (DHCP) letter in Australia to closely the content/elements with the Risk Evaluation and Mitigation Strategy (REMS) in the US. A detailed outline of the DHCP describing all relevant details and all educational materials to be used in Australia should be attached to an updated ASA and will be reviewed. In the US, A REMS is implemented to inform Healthcare providers about the serious risks of cytokine release syndrome, neurological toxicities, and medication errors. The REMS components consisted of: Blincyto REMS Letter for Healthcare Providers Blincyto REMS Letter for Hospital and Home Healthcare Pharmacists Blincyto REMS Fact Sheet for Healthcare Providers In Europe, following the feedback received from the CHMP evaluation, the sponsor has proposed to distribute educational materials to address the risks of neurological events (physicians, nurses, patients and caregivers) and medication errors (physicians, nurses, patients and caregivers, pharmacists). The educational materials will include: Educational brochure for physicians Educational brochure for nurses Educational brochure for patients and caregivers The sponsor proposes to provide the educational materials to health care professionals and to patients via health care professionals. They may also be supplied by the sponsor directly. In addition, according to the ASA, the sponsor proposes to conduct a market research study to measure the effectiveness of the educational program. The sponsor has committed to providing these results to the TGA and should do so as soon as practical after launch. Should reports of medication errors or serious adverse events occur, the sponsor will be
(including Patient alert card) Preparation guide for Pharmacists Based on the proposed European RMP materials, the sponsor will no longer be distributing a DHCP letter as an additional risk minimisation tool as originally planned; targeted educational materials will be disseminated instead (see Response to Recommendation 8). To align with the US REMS which also included include cytokine release syndrome, the Australian educational materials will also discuss this additional risk (not included in the European materials). All educational materials proposed for Australia are provided in the revised ASA. required to revisit these educational materials. Regarding the educational material for Doctors and Nurses, the sponsor should include advice to ensure that the patient/ caregiver receives the patient educational material and CMI. Recommendation 10: The ASA should be revised to include a risk minimisation activities table detailing all planned risk minimisation measures in the Australian context and the context. This table should include a comparison of the actual content and wording of the EU SmPC and the proposed Australian PI and CMI for all of the specified ongoing safety concerns and missing information to identify and provide reasons for any observed differences; particularly where it appears the EU Summary of Product Characteristics (SmPC) is more restrictive. A revised table detailing all planned risk minimisation measures in the Australian context and the EU-RMP context can be found in 2 tables of the ASA. Differences in the two documents have been justified accordingly. It should be noted that both the EU RMP and SmPC are still under evaluation and may be subject to further changes. The revisions made by the sponsor are acceptable in the context of this evaluation. Summary of recommendations Outstanding issues Issues in relation to the RMP Pharmacovigilance plan: Once the protocol for Study 20150136 is finalised, relevant details should be included in an update to the RMP (see Recommendation 5 of Table 4, above).