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Vaccines, Blood & Biologics

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Information Request Email, February 29, 2012 - ALLOCORD

 

 

From:        Tull, Lori
Sent:          Wednesday, February 29, 2012 3:32 PM
To:             'Donna Regan'
Subject:     Minutes from 2/22/12 telecon
 
 
Hi Donna,
 
Below are the minutes from your 2/22/12 telecon with Safa Karandish. She asked me to forward these so you would have her comments in writing.
 
Best Regards,
Lori
 
Lori A. Tull, RAC
Regulatory Project Manager
Office of Cellular, Tissue, and Gene Therapies
Center for Biologics Evaluation and Research
(301) 827-5359
 
 
Teleconference Minutes
 
Sponsor: St. Louis Cord Blood Bank (BLA STN 125413)
 
Date: 2/22/2012, 10:00am
 
Sponsor participants: Donna Regan, Kathy Fortune, Kathy Mueckl
 
FDA participants: Safa Karandish
 
The following items were discussed with the sponsor:
 
Maternal Infectious disease testing:
 
1.     In the Vendor Requalification document (QM. 05D.03), HIV-1 --------------------------------(b)(4)---------------------------------- HIV-2 ------------(b)(4)------------------- Syphilis --------(b)(4)-------- are marked as tests that are performed by ------------------(b)(4)-----------------. However, these tests are not included in table 45A of the application summary (page 111). Are these tests currently performed? If yes, please describe when the additional tests are performed, how the results are being factored into the donor eligibility determination and how are the results reported.
 
Sponsor will review the documentation and provide the requested information.
 
2.   For syphilis testing, please clarify whether you are performing a non-treponemal screening test (b)(4) followed by a confirmatory test or a treponemal donor screening test (-----------(b)(4)----------). Please address the following discrepancies and describe how positive results are factored into the donor eligibility determination:
 
a.      Tables 45A and 45B in the BLA summary (pages 112 & 113): refers to (b)(4) as well as ------(b)(4)------ system. 
b.     SOPs TE04.01, SLCI-CTS 4031.01 and SLCI-CTS 4030.01: refer to (b)(4) and treponemal confirmatory test (no information has been provided on the confirmatory test).
c.      Document titled “Information Available on Placental Cord Blood Unit: refers to (b)(4)
 
Sponsor confirmed that the test for syphilis is a -------(b)(4)-------- donor screening test. They will submit revised SOPs. 
 
3.   Please confirm whether or not the following test kit manufacturer information that is listed in table 45A of the BLA summary is correct:
 
a.      ------------(b)(4)----------- manufactured by -------(b)(4)---------
b.     CMV test kit manufactured by ------------(b)(4)--------------
If the above information is correct, please note that test kits from the two listed manufacturers are not approved, licensed or cleared by the FDA.
 
Sponsor will review the test kit manufacturer information and provide the requested information.
      
4.   Please provide the following information regarding maternal infectious disease specimens and testing:
 
a.      Please explain how maternal specimens are shipped to the testing laboratory (e.g. shipping container, temperature range and the acceptable time frame from collection of the samples to testing).
 
Sponsor will submit the requested information.
 
b.   In SOPs TS.01.08 & SOP SLCI-CTS 4030.01, there are references to supplemental and confirmatory tests. Please identify the supplemental and confirmatory tests that you perform and provide the test kit manufacturer information. Also, please describe how results from the confirmatory tests are factored into the donor eligibility (DE) determination. Please note that negative or a non-reactive result on a confirmatory test would not override a positive or reactive screening test except for syphilis.
 
Sponsor will review the documentation and provide the requested information and revised SOPs.
 
c.   We understand that you accept units from donors that test positive for (b)(4)HB(b)(4), if the result of the HBV(b)(4) is negative. In several SOPs, you have stated that the unit is labeled as “Exception”. Please note that donors with positive (b)(4)HB(b)(4) results are “ineligible” regardless of the (b)(4) HBV test results. Units from ineligible donors are not qualified for licensure but may be release under an IND, if there is a documented urgent medical need. Please revise and submit all applicable SOPs.   
 
Sponsor will review the documentation and provide the revised SOPs.
 
d.   Please describe how the birth mothers are assessed for possibility of plasma dilution prior to the collection of maternal specimens and how this information is documented and factored into the DE determination.
 
Sponsor explained that transfusion of blood and blood components are documented on the labor and delivery form. Units collected from birth mothers who have been transfused at the time of delivery are not stored for clinical use. Sponsor will revise SOP and forms to address cases that involve infusion of >2000ml of crystalloids within 1 hour of maternal specimen collection. 
 
e.   We understand that at the time of confirmatory testing, you perform CMV (b)(4) on cord blood samples if the maternal CMV --(b)(4)-- results are positive. Are results reported to transplant center?
 
Sponsor explained that the CMV (b)(4) is a research assay at St. Louis facility only. Results are added as a comment to the report that gets submitted to the transplant center. Sponsor will submit the report for review by FDA. 
 
Donor Eligibility
 
5.   Your donor screening procedures do not include review of birth mother’s relevant medical records for clinical evidence of RCDADs in accordance with 1271.75 regulations. Please submit revised SOPs that describe the process for review of relevant medical records for clinical evidence of RCDADs and how findings are factored in to the DE determination. You may refer to the Donor Eligibility Guidance, section IV.F for additional information.
 
Sponsor will submit the revised SOPs.
 
6.   In several SOPs and documents (e.g. CL.03.06, CL.13.08, TS.01.08, SLCI-CTS 4030.01, Cord Blood Collection Guidelines), you refer to terminology such “disclosure” or “exclusion” when certain risk factors are identified in donor screening and testing. We can not determine which identified RCDAD risk factor (except for risks identified on the maternal history questionnaire) would make a donor ineligible. We recommend that you revise SOP(s) and clearly define:
 
a.      The criteria for “eligible” donors based on the review of the medical history questionnaire, medical and physical examination records and the donor testing results. SOP should also specify that only units from eligible donors are acceptable for licensure.
b.     List of risk factors identified during the review of the medical and physical examination records, and the donor testing results that would make a donor “ineligible”. SOP should specify whether units from the ineligible donors are discarded or kept in the inventory for release under the IND, if there is documented urgent medical need.
c.      The criteria for donors for whom donor eligibility has not been completed (example: missing response to a donor history questionnaire, missing test result). SOP should specify whether units from the donors for whom donor eligibility has not been completed are discarded or kept in the inventory for release under the IND, if there is documented urgent medical need.
d.     Documentation of the final DE determination before listing the units in the search inventory.
 
Sponsor will submit the revised SOPs.
 
7.   Please clarify whether the release criteria listed in SOPs SLCI-CTS 4031.01 and TE04.01 are applicable only to licensed units or to all units that will get listed in the search inventory. We recommend that you distinguish the release criteria for units that will be used under an IND versus the licensed units and specify that only units from eligible donors will be acceptable for licensure. 
 
Sponsor will submit the revised SOPs.
 
Collection
 
8.   Please submit the following information for both facilities. If identical procedures are used, please specify:
 
a.      List of the components included in the collection kits including the collection instructions. 
b.     Describe how the expiration dates of the collection kits that are stored at the collections sites are tracked.
 
Sponsor will submit the requested information.
 
9.   Collection Validation
 
Even though the submitted paper from 1997 and the audit report for the Kansas facility are good supportive information, they do not adequately demonstrate the validation of your current collection procedures. We recommend that for both facilities (Kansas and St. Louis); you perform a prospective validation, using current SOPs, to analyze the critical collection parameters. The plan should define the number of consecutive units collected in a set time period, parameters to be evaluated and the acceptance criteria. The validation protocol and the validation summary report should be approved by the quality unit.
 
Sponsor agreed to develop a plan. Reviewer offered to review the draft validation plan prior to execution.
 
Transportation of collected units
 
10. Please explain why the two facilities use different methods for transportation of the collected units from the collection facilities to the processing laboratories (St. Louis: individual collection kits are picked up by the courier- SOP CL.17.08, Kansas: collection kits are placed in a “qualified transport cooler”- SOP SLCI-CTS 4039.01). We note that a digital thermometer is placed in courier vehicles and the courier is responsible for documenting the temperature at the time of pick-up from the hospital and delivery to the bank. Please explain how you ensure that the collected units are maintained within the acceptable temperature while in transit since there is no continuous temperature monitoring. 
 
Sponsor explained that the method for transporting individual kits has been implemented recently based on tracking and evaluation of available data. Sponsor also stated that the maximum transport time is about (b)(4) and the temperature is recorded at each pick-up stop. Sponsor was informed that the method may not be adequate. Sponsor will submit additional information including qualification data for the transport coolers (used in Kansas facility) for review.    
 
Unique Donor Identification
 
11. Please provide the following information regarding the unique donor identification barcodes:
 
a.      How are the numbers generated and what makes the number unique?
b.     How does the unique ID barcode that is assigned to the birth mother (maternal specimens) differ from the one assigned to the cord blood unit?
c.      How do you maintain linkage between the birth mother and the collected unit?
 
Sponsor will submit the requested information.
 
Additional request not discussed during the teleconference:
 
12. We understand that the collected units are placed in a designated locker when they are delivered to SCLBB and the lockers are equipped with a temperature data logger (SOP CL.17.08). Please describe how long the units may be kept in the locker, the acceptable temperature range and how the temporary storage temperature are evaluated for acceptance of units.
 
Sponsor was informed to send any draft document for review through Lori Tull.
 
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