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Vaccines, Blood & Biologics

Record of Telephone Conversation, October 11, 2012 - ALLOCORD


HPC, Cord Blood
SSM Cardinal Glennon Children's Medical Center
Telecon Date/Time: 11-Oct-2012 02:00 PM        Initiated by FDA? Yes
Telephone Number:
Communication Categorie(s):
1. Information Request
Telecon Summary:
Discussion of proposed media simulation, process validation plan and CMV validation information
FDA Participants: None
Non-FDA Participants: None
Trans-BLA Group: No
Related STNs: None
Related PMCs: None
Telecon Body:
 The following comments were sent to SLCBB prior to the telecon:
1) Your validation plan proposing to statistically compare data from (b)(4) prospectively selected CBUs to PrepaCyte-CB historical data is an acceptable approach to process validation. Please define your acceptance criteria prior to data collection.
2) In addition to the statistical data comparison, you should also add (b)(4)-processing TNC viability (b)(4) as an acceptance criteria.
3) For the thaw and reconstitution validation you should set a target acceptance value for viable cell recovery of at least 70% as specified on pages 29, 30 of the Cord Blood guidance.
4) We acknowledge that there may be data that occasionally falls below the target acceptance value for viable cell recovery, but for validation purposes it should remain within the acceptable range defined by your historical data.
SLCBB: They said that would include items 2 and 3 into their validation plan. The acceptance criteria for the processing validation study will be that the study has to produce data within (b)(4) standard deviations of the historical data.
FDA: We said this was acceptable. We also requested that data for each of the Cord Blood Units processed should be submitted, not just the summary. We also reminded them that the validation study should be done using the updated SOPs that will be implemented in response to the inspection observations.
SLCBB: They confirmed that they would do both of these.
Media Fill Process
DMPQ led a discussion for the Media Fill Process proposed by SLCBB.
SLCBB provided the following documents pertaining to their proposed media fill process:
  • QM.16.02 Media Fill Process
  • QM16A.01 - Growth Promotion and Sterility Testing of ---(b)(4)--- Broth for Media Fill
  • QM.16B.01 - ---(b)(4)--- Broth Growth Promotion Testing Under Simulation Conditions for Media Fill 
QM.16.02 Media Fill Process
SLCBB explained the (b)(4) methods they proposed for the media fill. Method (b)(4) and Method (b)(4) are typical of what is seen for media fills. -----------------------------------------------------------------------------------------------(b)(4)------------------------------------------------------------------------------------------------------------.
DMPQ found Method (b)(4) and Method (b)(4) to be acceptable. The expectation that SLCBB will use the approved -----------------------------------------------------------------------(b)(4)------------------------------------------------------------------ was conveyed to SLCBB. It was also clarified that growth promotion testing would be expected to be performed -------------------(b)(4)----------------------------------------------. The expectation of performing environmental monitoring, including personnel monitoring, during the media fill was discussed with SLCBB.
QM16A.01 - Growth Promotion and Sterility Testing of -----(b)(4)----- Broth for Media Fill and QM.16B.01 - ---(b)(4)--- Broth Growth Promotion Testing Under Simulation Conditions for Media Fill  
These are blank data forms provided by SLCBB to illustrate the information that will be captured by the microbiology lab during media testing and media fills. Overall, the forms appeared to be acceptable; however, DMPQ suggested that SLCBB capture the Equipment ID number for the incubators used along with the Lot number (or however SLCBB ID’s their raw materials) for the --------(b)(4)-------- plates used.
Process Validation
Process validation was briefly discussed by DMPQ. A more in depth discussion was conducted by the Product Office.
SLCBB provided the document, Process Validation for manufacturing of Unrelated Umbilical Cord Blood Products: Design Proposal. The design proposal is a high-level document describing SLCBB’s approach to process validation. DMPQ reiterated the expectation that the final approved batch production record would be used during the validation. It was noted during the discussion that the plan appeared to be lacking in information describing a plan for what would be done if any of the acceptance criteria were not met, such as an investigation, if applicable. In addition, the process validation proposal did not include information pertaining to personnel responsibilities for review and approval of the final process validation report and under what conditions will the process have to be revalidated.
Validation of the CMV (b)(4) testing
In an email dated 9/20/12, SLCBB provided a response related to the CMV (b)(4) validation deficiency that was included in the FDA Complete Response letter dated August 16, 2012. SLCBB explained that they did not consider the CMV (b)(4) testing that is performed on a ----(b)(4)----- sample as a release criterion. They stated that the test is performed ------------------(b)(4)-------------------. SLCBB provides the test results to the transplant physician ------------(b)(4)------------. The physician then makes the final decision regarding the acceptance of unit based on the test results. SLCBB also indicated that the test is performed by the CAP-accredited Virology Laboratory at SSM Cardinal Glennon Children’s Medical Center. SLCBB submitted a letter from the Virology Laboratory (dated 12/21/2009), which provides a summary of the assay, limit of detection and validation studies performed using ----------------(b)(4)--------------. 
FDA: We explained that even though the assay is performed -------------------(b)(4)------------------; the physicians are making a clinical decision based on the test results provided by SLCBB. Therefore, the CMV (b)(4) assay must be validated. We also pointed out that the Virology Laboratory letter indicated that the validation studies were performed using --(b)(4)-- sample collected --(b)(4)-- and not -------(b)(4)------- specimens.
SLCBB: After some discussions, SLCBB stated that they would no longer perform the CMV (b)(4) assay. Instead, they would provide a -----(b)(4)----- sample to transplant center for testing. 
FDA: We said that this was an acceptable approach.           

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