From: Tull, Lori
Sent: Wednesday, July 11, 2012 1:23 PM
Subject: Fw: Status of requests sent to St. Louis in Feb
Safa's comments are below.
From: Karandish, Safa
Sent: Wednesday, July 11, 2012 12:11 PM
To: Tull, Lori
Subject: FW: Status of requests sent to St. Louis in Feb
Here is my list of comments. I also updated the status of my prior request (see 2/29/12 email below).
1. Draft form CL.03B.08 Labor & Delivery Data- Please clarify whether you exclude mothers who
have ever had positive serology for syphilis or gonorrhea, even if it was treated?
2. Please address the following discrepancies in the draft SOPs:
- CL.13.10: P 4, step 3: According to donor questionnaires and SOP TE04.03, you accept donors with
history of travel to certain risk areas but donors are determined ineligible and units are used under
IND. In step 3, you state that units from ineligible donors are discarded or used for research.
- TE.04.03: P3, step 5: Donors with positive HB(b)(4) or travel history to certain risk areas are ineligible
and units are made available for transplant under IND. However, on P 5, Procedure Note section, you
state products from ineligible donors are discarded or retained for research use.
3. In draft SOP CL.06.08 and the Labor and Delivery form, you have included documentation of >2000 ml
IV fluid infusion prior to obtaining maternal test samples. In the SOP, you should define how that
information is factored in to the DE determination (unit discarded or donor is ineligible but unit released
4. Draft SOP CL.03.07: P3, step e: Please clarify whether donors with the listed findings are considered
"eligible" or "ineligible" for DE determination purposes. We also note that you disclose if mother/infant
has elevated temperature or received antibiotics during labor. We suggest that you clarify that he
conditions are acceptable only in absence of any suspicion related to infection.
5. Draft Product Documentation/Tech Review form: Under DE section, suggest adding "Incomplete"
category. Under Unit Disposition section, suggest clarifying whether the available units are licensed or for
release under IND.
6. Please submit an example of the Comprehensive report that includes the CMV (b)(4) results.
From: Donna Regan [mailto:firstname.lastname@example.org]
Sent: Wednesday, February 29, 2012 4:52 PM
To: Tull, Lori
Subject: RE: Minutes from 2/22/12 telecon
Thank you, Lori.
From: Tull, Lori [mailto:Lori.Tull@fda.hhs.gov]
Sent: Wednesday, February 29, 2012 2:32 PM
To: Donna Regan
Subject: Minutes from 2/22/12 telecon
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.
Lori A. Tull, RAC
Regulatory Project Manager
Office of Cellular, Tissue, and Gene Therapies
Center for Biologics Evaluation and Research
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. Response
2. 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)------. Revised tables submitted specifying -------(b)(4)---
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
Draft SOP TE04.03 submitted, reference to (b)(4) deleted. Updated Kansas facility
SOPs not submitted.
c. Document titled ?Information Available on Placental Cord Blood Unit: refers to
(b)(4) Revised document submitted, section deleted.
Sponsor confirmed that the test for syphilis is a -------(b)(4)---------- donor screening test. They
will submit revised SOPs.
3. 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. Revised document submitted, manufacturer info corrected.
4. 4. Please provide the following information regarding maternal infectious disease specimens
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. SOP TS.01.09 (St. Louis facility)
submitted. Kansas City facility SOP not submitted.
b. 5. 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. Revised SOP TS.01.09 submitted. Section related to confirmatory tests deleted. Updated
Kansas City facility SOPs not submitted.
c. 6. 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. Draft SOP CL.13.10
d. 7. 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.
Draft SOP CL.06.08 and L&D form submitted . See comment above. L&D form used by
Kansas City facility not submitted .
e. 8. 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
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. Revised SOP SE.01.09 submitted. See comment above.
5. 1. 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. Revised CL03B08 form submitted. See
6. 2. 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
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
Sponsor will submit the revised SOPs. Draft SOPs CL.03.06, TE04.03, CL13.10,
Product Documentation/Tech review form and SOP TS.01.09 submitted. See comment
No information submitted for Kansas City facility.
7. 3. 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
Sponsor will submit the revised SOPs. Draft SOP TE04.03 submitted. See comment
above . No information submitted for Kansas facility.
8. 1. 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
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. SOP CL.15.05 submitted. Kansas
City facility SOP not submitted
9. 2. 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. Proposed plan received for review
Transportation of collected units
1. 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
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. Response pending.
Unique Donor Identification
1. Please provide the following information regarding the unique donor identification
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. Response pending
Additional request not discussed during the teleconference:
1. 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. Response pending.
Sponsor was informed to send any draft document for review through Lori Tull.
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