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U.S. Department of Health and Human Services

Vaccines, Blood & Biologics

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Mid-Cycle Agenda, October 18, 2012 - HPC, Cord Blood BLA 125432

 

Sponsor:          LifeSouth
BLA #:                              BLA 125432
Product:           HPC, Cord Blood
Time:                 11:00-12:00 PM
 
Meeting Attendees: Candace Jarvis, Juanita Williams-Gould, Mohammed Heidaran, Eric Dollins, Karoll Cortez, Fatima Abassi, Jalal Sheikh, Mark Borigini, Stan Lin, Shamsul Hoque, Loan Nguyen, Chad Berger, Keith Wonnacott, Mercedes Serabian, Changting Haudenschild, Lisa Stockbridge, Marion Michaelis, Joydeep Ghosh, Safa Karandish, Lillian Ortega, Patricia Holobaugh, Ilan Irony, Wilson Bryan, Stephanie Simek, Kimberly Benton, Raj Puri, Celia Witten, Patrick Riggins, Lori Tull, Ted Stevens, Ke Liu, Angela Hall,
 
 
Call in information:  -------------(b)(4)------------------------------
 
 
Agenda
 
1.           Administrative
 
·           Introduction of Chad Burger. He replaces Grace Deneke in DMPQ
·           Draft Review Memos- If you have not turned one in, please do so.
·           Managers may have to provide updates for Celia from today’s meeting
 
2.           Official Milestones and Monthly Goals
 
The current due date: Monday, March 18, 2013 (10 month clock)
 
Draft Review Memos to Celia: Thursday, October 11, 2012 (PAST DUE)
Mid-cycle Review Meeting: Thursday, October 18, 2012
Monthly Team Meetings: Scheduled the last Monday of Each Month
Final Concurred Review Memos: Thursday, January 17, 2013
Wrap-up Meeting: Tuesday, February 19, 2013
Labeling Meeting: TBD (To be Discussed?)
Lot Release Clearance: Monday, February 18, 2012
 
3.          Overview of outstanding deficiencies: By review discipline, the following are major deficiencies that have not been adequately resolved:
 
Pharm/Tox
 
1.     No outstanding deficiencies.
 
Clinical
 
1.     No out standing deficiencies
 
CMC
 
*Note: A t-con was held with the sponsor to discuss items 1-3 and there has been some follow-up; however, their updated SOPs that were requested still need to be verified
 
1.     Donor screening SOPs need to be revised to provide detail information regarding review of the medical and physical examination records
 
2.     Collection validation information not adequate. The applicant has not provided all the data.
 
3.     The applicant must provide information regarding the assignment of unique donor identification and maintaining linkage between the collected unit and the birth mother.
 
4.     Sponsor to provideanalytical specificity and analytical sensitivity for CD34 and nRBC enumeration laboratory validated tests.
 
5.     In regard to the (b)(4) sterility test method validation, the adequacy of the sampling plan for the final product has not been adequately established.
*The sponsor does not test the by-product, but test the final product.
 
6.     Package label is not in compliance with ISBT 128 requiring bar codes.
*Sponsor states that they cannot create barcodes
 
7.     Request for proprietary name is outstanding.
 
8.     Revalidation of the Emergency Recovery remains to be performed.
 
9.     Revalidation of the collection kit transport from collection site to the processing canter is not yet completed (see DMPQ IR question 25).
 
 
DMPQ / Facilities
 
1.     We still have not received the 483 responses from the inspectional findings (due 10/19/12) issued on the 483 at the conclusion of the pre-licensed inspection. The 483 was issued on 9/28/2012 and the firm is due to respond within 15 working days from the close of the inspection with their plans for corrections. This means that the response should be coming very shortly since we are at about the 15 day.
 
 
4.           Other Updates:
 
a.                P/T:
  • There is no PT outstanding issue with this BLA. Review is completed and with supervisor for concurrence. (Note: The final concurred review due date is January 17, 2013).
  •  All the container closure systems including Collection bags with CPD, ------(b)(4)-------------------------, freezing bags are FDA approved or cleared. No PT issue
  • Labeling: reference was made to page 1 of 8 of the PI, under section “Use in specific populations”, Proposal to modify or remove the sentence “Pregnancy: based on animal data, may cause fetal harm. Use only is clearly needed. (8.1)”. There was a discussion within the team members. The labeling group stated that this is from the CFR and part of the standard PI (???)- should stay as is. The team decided to revise this in the future, and subsequently correct all the previous cord blood labeling
CLINICAL: 
  • There are no clinical issues that prevent an approval recommendation for this application
  • We will not ask for any additional clinical information from the applicant. There were only about 80 CB transfusions with the LifeSouth product, and substantial missing data in all variables (successful hematopoietic reconstitution / engraftment, infusion reactions, GVHD, etc). We will work with what we got already
  • At this point of the review, it is unlikely the label will show any of the data from the LifeSouth cord blood experience. So it will be only the class product data that are already presented in the approved cord blood labels
  • We will likely have the concurred clinical and statistical reviews ready before Christmas and ready to discuss the clinical portions of labeling internally and in January 2013 with the applicant
 
b.               CMC: 
  • Sponsor batch records need to be updated,
  • Lab records appear to be ok
  • Sponsor needs to incorporate critical process parameters
 
c.                DMPQ:
  • The inspectional findings for facilities issues, such as the deficiencies in the cleanroom construction are a concern. Fixing the unsealed window and inadequate flooring in the------- (b)(4) area would most likely result in a renovation of the cleanroom and they would have to requalify the room after the renovation and this could take some time. Additionally, growth promotion testing on media used for media fills and environmental sampling needs to be performed according to a standard referenced method and LifeSouth needs to identify environmental facility isolates. Also improvements to the batch record may take some time as well.
  • The team asked DMPQ if they believe that LifeSouth could address the deficiencies within the review timeframe. DMPQ responded that they would have to wait until the firm submits their 483 responses and see the projected completion dates. DMPQ indicated that if it is close to the due date it may be feasible to ask for a major amendment extension.
  • DMPQ also raised the issue that the team should discuss what manufacturing capacity we are approving LifeSouth for. They are currently manufacturing ---(b)(4)-- HPC-C units a day. After approval their plans are to increase ---(b)(4)--. I believe that they should come in with a PAS for this increase since while on inspection the team had concerns about LifeSouth’s ability to manufacture at the increased capacity
 
d.               STATS:
  • Requested information on terms/definitions in submission; Rec’d on 10/18/12-appear to be ok
 
e.                LABELING:
  • No new updates
 
5.               Other Issues/Questions for Sponsor Discussion:
 
6.               Action Items
 
  • Set up internal labeling meetings starting in January 2013
  • Send PI from Duke BLA to review team
  • Pregnancy section of PI needs to be revised to reflect that non-human testing is not performed