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Vaccines, Blood & Biologics

Record of Telephone Conversation, December 13, 2012 - HPC, Cord Blood BLA 125432


Submission Type: BLA    Submission ID: 125432/0    Office: OCTGT
HPC, Cord Blood
LifeSouth Community Blood Centers, Inc.
Telecon Date/Time: 13-Dec-2012 09:00 AM        Initiated by FDA? Yes
Telephone Number: ---------(b)(4)----------------------------------------
Communication Categorie(s):
1. Information Request
2. Advice
Telecon Summary:
Teleconference to discuss Donor Eligibility and Collection; sterility protocol, general discussion
FDA Participants: Mohammad Heidaran, Ph.D., Biologist (CBER/OCTGT/DCGT)
      Eric Dollins, Ph.D., Biologist (CBER/OCTGT/DCGT)
      Joydeep Ghosh, Ph.D., Microbiologist (CBER/OCTGT/DCGT)
      Candace Jarvis, B.S., CSO (CBER/OCTGT/RMS)
      Safa Karandish, B.S. MT (ASCP). CSO (CBER/OCTGT/DHT)
Non-FDA Participants: ill Evans, (Vice President of Quality)
                                     Amy Lambert, (Manager Cellular Therapies)
                                     Tammy Lawson, (Validation Coordinator)
 Ed Downey, (Administrative Laboratory Manager)
 Evan Basler
 Louis Hernandez
Trans-BLA Group: No
Related STNs: None
Related PMCs: None
Telecon Body:
FDA requested a teleconference with Life South to discuss their donor eligibility and collection. A copy of this document was sent via email to the sponsor prior to the teleconference.
Follow-up comments to responses received regarding October 2, 2012 teleconference items (Addendum # 4):
We suggest that you clarify the following in your SOPs and forms and submit the revised documents (Please note that we tried to follow the numbering format that you used in your response letter. That is the reason for references to different item #s in the following list):
  1. Item # 11 and # 1 (item #14), SOP CB-MO.1.5:
    1. Step 1, reference to vCJD risk in the table- Please note that a donor with vCJD risk is ineligible. Stating that CBU is eligible for banking but not licensable is confusing. We suggest that you state the donor is ineligible and therefore not qualified for licensure. However, the unit can be banked for use under IND.
    2. Step 2f- Please clarify “other medical information” that would be considered as exclusion criteria.
    3. Step 6, information in the table- Please note that the use of a product from an ineligible donor is allowed by the regulation under an IND if there is documented urgent medical need. Use of a unit from an ineligible donor should not be considered a “variance”.
Sponsor Response: The sponsor stated that they will comply with FDA’s request and submit the revised documents.
  1. #2 (Item #15), COA:
    1. Please correct the regulation citations for infectious disease testing. You should only include 1271.80 and 1271.85.
    2. In the specification column for the infectious disease testing, you should state “All tests negative except for CMV” because you have listed CMV in a separate row.
    3. For Donor Eligibility Determination, in the specifications column, you should state “eligible” and delete the existing statement.
Sponsor Response: The sponsor stated that they will comply with FDA’s request and submit the revised documents.
  1. Cord Blood collection (#6a, #6c: SOP CB 2.2, CB 7.1.2):
    1. For criteria of a bankable unit, you refer to CBU Weight and TNC level Requirements reference document. This document defines the minimum gross weight of the product. We note that in your response to our July 16, 2012 letter, you indicated the minimum volume is --(b)(4)--; however, we have not seen the minimum acceptable cord blood volume defined in any of your submitted SOPs. Please add the minimum acceptable volume requirement to the appropriate SOP and address the following:
                                                    i.     Explain the difference in the minimum gross weight requirement listed on the reference document (--(b)(4)--, in foot note: ---(b)(4)--------- from April 8, 2010 through June 5, 2011 and ---(b)(4)------ from June 6, 2011 through July 6, 2012).
                                                  ii.     In response to our July 16, 2012 letter, for item #18c, you indicated minimum acceptable volume is --(b)(4)--; however, for item #24 in the same letter, the minimum acceptable volume was (b)(4).
Summary of Discussion: FDA requested clarification on the minimum volume requirement for bankable units as it is not defined based on weight which keeps changing and is not easily located in their responses. The sponsor stated that they will define it in the SOP for processing SOP 7.2.4 and on the reference document 7.3.2 . FDA emphasized that the minimum acceptable criteria for TNC and volume must be specified on the batch record.
    1. SOP CB 2.2: We understand that unit bankability (CBU weight and TNC criteria) is determined at the processing laboratory (LifeSouth’s Headquarters), and the mother is consented only if the unit is bankable. Please explain how the information regarding bankability of the unit is communicated to the staff responsible for obtaining the consent. Please submit applicable SOP(s) that describes this process.
Sponsor Response: The sponsor stated that they will submit the SOP that describes this process.
  1. We have reviewed the documents that you submitted regarding the assignment of donor identification numbers (DIN) to the unit and the birth mother specimens. We understand the process for the assignment of the DIN to the cord blood unit; however, we have concerns about how the DIN is assigned to the birth mother’s specimens and maintenance of linkage between the two. The following are just few examples of inconsistencies that we are concerned about:
    1. On the process flowchart (page 2, attachment I), it appears that the staff at regional facilities determine bankability of the unit and assignment of the maternal DIN. Our understanding from your prior responses is that these steps are only performed at the processing laboratory (corporate facility).
    2. Use of last 4 digits of SS#- we do not understand how the use of the last 4 digits of SS # properly identifies an individual. 
    1. On the collection form (Attachment I, page 4), you have noted that the last 4 digits of mother’s SS# is used to link mother to the baby but in your response letter (item #12), you stated that the note entered in the IBBIS records maintains linkage between the CBU DIN and the maternal DIN. Please note that entering a comment in to your computer system is not adequate for maintaining linkage.
    1. In your response to item #11, you state that the collection form is labeled with the unique maternal DIN. However, in SOP CB.8.1, there are no instructions for placing the maternal DIN on the collection form when the DIN is assigned. To properly maintain linkage, we suggest that when the maternal DIN is assigned, the maternal DIN sticker to be placed on the collection form that already includes the CBU DIN.    
    1. SOP 9.1- Step 2b- We have concerns about the instructions in the table related to updating the maternal SSN or demographics. You have not described your verification process for maternal identification before making any changes in your system.
Summary of Discussion: The sponsor stated that the regional staff is not performing the counts to determine the unit bankability. The sponsor further explained that the maternal DIN may be assigned by the regional staff but the DIN is not placed on the copy of the collection form that accompanies the maternal samples. The sponsor acknowledged that the process for maintaining linkage needs to be better defined and stated that they were clear about the FDA questions. The sponsor also stated that the use of last 4 digits of mother’s SS# is no longer applicable and they would remove it from the documentation. FDA asked the sponsor to send in a flow diagram that clearly describes the process for the assignment of maternal DIN and maintaining linkage with the unit DIN including references to all associated SOPs. FDA reiterated that they take a look at SOP 9.4.1 as it refers to the social security number and that the SOPs and forms need to be updated. The sponsor stated that they will comply with FDA’s request.
We would like to discuss the step-by-step process for assignment of the maternal DIN and the linkage documents. For our discussion, please have the following documents available:
-        Attachment I (Handling Maternal Sample Tubes- process document, Process Flowchart, CB5.3, CBU Collection form, CB8.1 and CB9.1.).
-        Response letter (addendum 11/14/2012)
F FDA asked for a timeframe as to when they would be providing their sterility protocol for review. The sponsor stated that they would be providing it via email this afternoon.
The sponsor had concerns with the maximum size of the collection bottle and had the following questions: 1) what is the acceptable volume and 2) what ratio of RBC to plasma is acceptable. FDA asked how much RBC is left over and the sponsor responded between (b)(4) is left over after doing all other tests. FDA stated that they would like to see a minimum 50/50 ratio and an (b)(4) test sample volume would be OK as that is the maximum recommended test sample volume for the ----(b)(4)--------- bottles.
The sponsor also had questions regarding pooling different lots of cord blood by-product for the validation study. FDA asked them to send in their proposal and relevant justification for comments. 
The sponsor asked about continuing a pre-processing sterility test. FDA recommended them not to do the pre-process testing as with a very small inoculum size the tests are not useful majority of the time.
FDA asked the sponsor what was the status of their ISBT implementation. The sponsor stated that they have met with the vendor and is in the process of purchasing the software and asked if they could send in a copy of the label again. FDA stated that they would review the mock label and to be sure to send in the container and package label for review
FDA reminded the sponsor about their commitment to place a min/max thermometer in the shipping containers used for transportation of collected cord units to the processing laboratory. In regard to the batch record, FDA reminded LifeSouth to include the most updated SOP specifying the minimum acceptable cord weight for further processing.
The call ended cordially.

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