Record of Telephone Conversation, January 6, 2012 - ALLOCORD
Hematopoietic Progenitor Cells, Cord (HPC-C)
SSM Cardinal Glennon Children's Medical Center
Telecon Date/Time: 06-Jan-2012 04:00 PM Initiated by FDA? Yes
Telephone Number: ----(b)(4)-----
1. Information Request
Author: BRENTON MCCRIGHT
Request for additional CMC information
FDA Participants: Brent McCright, Brian Niland
Non-FDA Participants: Donna Regan; Dr. Salem Akel; Kathy Fortune; Melissa McKenna; Bill Ward
Telecon Body: The following comments were emailed to the St. Louis Cord Blood Bank (SLCBB) prior to the telecon to allow them time to formulate a response.
To facilitate the review process, we would like to request the following information.
- Additional information concerning the cord blood processing and lot release testing SOPs used at the Kansas City, St. Luke (SLCI) manufacturing facility is needed.
- Please identify the contractor SLCI uses for hemoglobin and HLA testing.
Sponsor response: They are using the same hemoglobin and HLA testing contractors as (SLCBB).
- Please supply the SLCI SOP for viable nucleated cell testing and the colony forming assay.
Sponsor response: They are using the same ----(b)(4)---- SOP. The SOP for the -(b)(4)- viability assay has been submitted in conjunction with their CD34 determination SOP.
- Please specify the cord blood manufacturing processes where the SLCI SOPs are identical to St. Louis (SLCBB) SOPs. Please refer to specific SLCBB SOPs that have been submitted.
Sponsor response: They are using identical SOPs as (SLCBB).
The SOPs for
- Your proposed potency assay will enumerate Total Nucleated Cells (TNC) using the ---------------------------(b)(4)---------------------------. You have provided data intended to support validation that includes enumeration of some individual cell subsets without clear comprehensive totals of nucleated cell numbers. Please clarify your definition of TNC used for product release and provide all relevant SOPs (SLCI and SLCBB) for your TNC enumeration.
Discussion: The Sponsor stated that the -------(b)(4)-------- only measured ---------(b)(4)--------- which will then be added together to get a TNC (total nucleated cell count). Therefore they thought they should only provide validation data for -------(b)(4)------- enumeration separately and not TNC enumeration.
FDA: We realize that their instrument measures --------(b)(4)-------- but since the lot release specification is TNC, they need to validate their assay using TNC as the final output, for at least a portion of the data.
The Sponsor agreed to provide validation data where they determine TNC.
- For both SLCI and SLCBB sites, please clarify how you decide whether to use ----------(b)(4)----------- for viable nucleated cell testing. Please provide viability (both methods) validation data for both SLCI and SLCBB sites.
Sponsor: ---(b)(4)--- is the primary method used for TNC viability testing although they also obtain viability data when they measure CD34+ cells – using -(b)(4)-.
- Please provide infectious disease validation data for the Community Blood Center.
Sponsor response: They will provide.
- Please provide validation data for the HLA typing and hemoglobin analyses which are performed by outside contractors. Supporting information should include proficiency test results, methods used, and contractor accreditations/certifications.
Sponsor response: They wanted more details on what we wanted.
FDA: We told them we wanted to see some data, perhaps a portion of the data the sites used for accreditation. We also wanted some further explanation of the methods used for testing.
The telecon ended with SLCBB saying that they have received clinical data from CIBMTR (Center for International Blood and Marrow Transplant Research) that they forward to us shortly. This data will include age of units used and degree of HLA match. They also mentioned “Data Writing”.