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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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First Committee Meeting Summary, October 18, 2012 - BAT

Date:                     October 18, 2012

From:                    Nannette Cagungun CBER/OBRR/DBA, HFM-380
 
To:                     125462/0
 
Subject:          Botulism Antitoxin Heptavalent (A,B,C,D,E,F,G)- Equine BLA
 


 
CBER Participants:
Marthe Bryant
Nannette Cagungun
Karen Campbell
Howard Chazin
Christine Drabick
Robert Fisher
Irwin Feuerstein
Erica Giordano
Judy Li
Anthony Lorenzo
Cynthia Kelly
Michael Kennedy
Dorothy Scott
Margaret Norton
Iftekhar Mahmood
Alpita Popat
Evi Struble
 
Discussion:
 
  • This product will replace the previous licensed botulism antitoxin that is no longer in use. Cangene is the contract manufacturer for the US Government (BARDA). 
  • This product is the first and only CBER product to be reviewed under the Animal Rule to date. The BLA has considerable human data and includes 2 pivotal animal studies.  The product was granted an orphan designation in June 2011.  
  • This BLA will include 2 clinical pharmacology reviewers. The review committee will request a veterinary consult reviewer if needed.
  • SAS datasets have not been provided for the confirmatory study. 
  • The review committee noted that the human data from CDC’s use of the product under its expanded access program (IND 6750) are less than ideal.  
  • The proper name, Botulism Antitoxin Heptavalent (A,B,C,D,E,F,G)- Equine, might need to be tweaked.
  • The proposed proprietary name, H-BAT, will be reviewed for acceptability. The use of a modifier may increase the chance of medication errors with future products because modifiers are routinely dropped.
  • DBSQC will draft the lot release testing plan.
  • There are already 80,000 doses of product stockpiled. 
  • Cangene should provide CBER with information on which lots they plan to submit for release. Monovalent bulks have been manufactured. Cangene is just blending now. CBER will ask the applicant to provide a blending schedule for the lots. No additional testing will be performed on these lots. Testing was done before these lots were placed in the SNS. Lots are placed on stability.
  • BIMO and CRB will look at the human safety study. BIMO will verify the animal data from the two pivotal studies and will run that by the LPD reviewers.
  • There are no toxicology studies in the BLA.
  • Robert Fisher will review the guinea pig studies and Michael Kennedy will look at the primate efficacy studies.
  • DMPQ will recommend a waiver of pre-licensure inspection.  
  • An FDA inspection should be considered prior to the manufacture of the next bulk product.   CBER needs to see the Installation Qualification (IQ) and Performance Qualification (PQ) for future inspection of the manufacturing line.  
  • The BLA contains a single PK study in adult human subjects. The clinical pharmacologists will review PK in animals (guinea pig and non-human primates) and extrapolate human dose from the animal PK studies.
  • The BLA contains a pharmacovigilence plan and a plan to conduct a study in case of mass exposure to the botulism toxin. OBE noted that the best way to do this is through a postmarketing study commitment.
  • It should be made clear to the applicant that PMCs are required under the animal rule. They should make a good faith effort to collect data to fulfill the PMCs.  
  • This BLA will go before BPAC in February 2013. The focus will be on the animal challenge model. The review committee should notify the Chair and the RPM if the advisory committee needs to weigh in on any issues.
  • The filing meeting is scheduled for October 24, 2012. The RPM and Chair will determine an appropriate format for that meeting.
  • Members of the review committee should complete their mid-cycle review memos by December 12, 2012. 
  • A labeling meeting will be scheduled shortly.
  • The press release should be drafted by January 2013.
  • Reviewers should make an effort to complete their executive summaries by the beginning of February 2013. These summaries should capture substantive elements of the review.
  • The review committee was reminded to include the STN number on the subject line of emails pertaining to this BLA.