Submission Type: BLA Submission ID: 125462/0 Office: OBRR
Botulism Antitoxin (Equine), Heptavalent (A, B, C, D, E, F, G)
Telecon Date/Time: 22-Jan-2013 12:00 pm Initiated by FDA? No
Author: NANNETTE CAGUNGUN
Pharmacovigilance surveillance through a registry
FDA Participants: Marthe Bryant, Nannette Cagungun, Irwin Feuerstein, Robert Fisher, Nisha Jain, Wei Hua, David Rouse
Non-FDA Participants: Hugo Astacio (Manager Pharmacovigilence), Tim Babinchak (Medical Director, Angela Dyer (Director Regulatory Affairs), Amber Fallon (Project Manager Regulatory Affairs), Christine Hall (Director Clinical Research), Allison Kennedy (Project Manager Regulatory Affairs), Terry Kraynyk (Manager Regulatory Affairs), Steve McGregor (Technical Specialist Regulatory Affairs), Reem Rahil Khazen (Regulatory Affairs Associate), Jeannette Rosolowich (Director Project Management), Darren Ross (Manager Government Programs), Laura Saward (Chief Scientific Officer), Chris Sinclair (VP Strategic Planning and Operations), Stephanie Sproule (Manager Clinical Research)
Scott Hancock, James Little, Steve Morris, Melissa Willis
FDA stated that postmarketing studies are required for approval of this BLA. 21 CFR 601.91 (4)(b)(1) states, “…The applicant must conduct postmarketing studies, such as field studies, to verify and describe the biological product's clinical benefit and to assess its safety when used as indicated when such studies are feasible and ethical. Such postmarketing studies would not be feasible until an exigency arises. When such studies are feasible, the applicant must conduct such studies with due diligence. Applicants must include as part of their application a plan or approach to postmarketing study commitments in the event such studies become ethical and feasible.”
FDA asked Cangene to create a patient registry to capture safety and clinical benefit during the first 3 years of product approval. This registry can lay dormant until an emergency occurs at which time it can be reopened. Cangene should submit a proposal in writing with the parameters that would be captured for FDA review.
Cangene asked for the number of patients that FDA anticipates for this registry. FDA responded that the number will depend on how many patients receive the product. FDA stressed the importance of capturing additional safety data because Cangene has a limited safety database.
FDA also asked Cangene to collect serious adverse events (SAEs) (both labeled and unlabeled) as 15-day reports post-licensure. FDA will further discuss with Cangene the SAEs that should be captured. FDA also asked Cangene to collect non-serious events related to hypersensitivity, allergies, bradycardia, and febrile reactions. Cangene noted that this discussion has clarified #41a of the December 21, 2012 information request. With regard to item 41b of the information request, Cangene agreed to obtain contact information of BAT requestors from CDC in order to conduct a more proactive follow up of treated patients.
Regarding item 41c which asked Cangene to include patients that received the product under the IND expanded access program, Cangene asked whether they should retrospectively go back to the CDC expanded program data. FDA said that Cangene will not have to do that if a patient registry exists. However, FDA might need some information that resides in the CDC database. Cangene should consider how CDC data can be obtained to enhance the surveillance program.
Cangene stated that it is committed to providing an updated statistical report from the CDC data and can still do that. They asked what outcome measures the FDA would like to see.
FDA requested Cangene to submit a proposal with a protocol outline that includes timelines for final protocol submission, study initiation date, and final report submission.
Cangene has submitted the analysis of CDC data up to the end of 2011. This includes safety analysis, safety and efficacy outcomes, duration of hospitalization, and time on ventilator.
Given that the registry would allow it to collect data for mass exposure, Cangene asked if data collection could be postponed. FDA said it could and explained it was requesting a detailed analysis plan so that data can be collected once mass exposure occurs. The proposal should include modeling or simulation.
Cangene stated that without knowing what a mass exposure could look like, it would like a dialog with FDA, CDC, and BARDA to discuss the design of the modeling or simulation scenario. FDA agreed to a dialog.
FDA noted that Cangene has modeling in the IND that is already being used so the firm does not have to start from scratch.
FDA will provide comments for the postmarketing studies to Cangene later this week in the form of an information request. Cangene asked FDA to consider the timing of their response because of the BPAC presentation.
The telecon ended.