Submission Type: BLA Submission ID: 125462/0 Office: OBRR
Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G) -(Equine)
Telecon Date/Time: 10-Dec-2012 04:00 PM Initiated by FDA? No
1. Information Request
Author: ROBERT FISHER
Discussion regarding HBAT dosing in animal models
FDA Participants: Robert Fisher, Michael Kennedy, Dorothy Scott
Non-FDA Participants: Terry Kraynyk, Chris Sinclair, Deborah Douglas, Laura Saward, Darren Ross, Steve McGregor, Terry Kraynyk, Reem Rahil Khazen
Trans-BLA Group: No
Related STNs: None
Related PMCs: None
Cangene was asked to clarify their definition of a 1x scaled human dose for the animal studies and justify the use of 1 vial considering the varying potencies of the two product lots used in the pivotal animal studies. Based on the potency of the lots, FDA was considering if two doses of product would be necessary to ensure an adequate dose in humans. Cangene explained that their dose scaling was on a weight/weight basis: allometric scaling was not used in the initial dose selection. The animal dose was determined by dividing 1 vial by a 70kg nominal human weight, and adjusting the dose to the animals based on their weight.
If allometric scaling is applied (based on conversion factors provided in the 2005 FDA guidance on a maximum safe starting dose in adult volunteers), the actual potency (human equivalent dose) delivered in the animal studies is less than the minimum potency as stated in the BAT label claim.
Cangene was asked to provide the details of the human equivalent dose calculations for the lots of BAT used in the animal studies.