The content on this page is provided for reference purposes only. This content has not been altered or updated since it was archived.
Vaccines, Blood & Biologics
Submission Type: BLA Submission ID: 125413/0 Office: OCTGT
HPC, Cord Blood
SSM Cardinal Glennon Children's Medical Center
Telecon Date/Time: 11-Jul-2012 02:00 PM Initiated by FDA? Yes
Author: BRENTON MCCRIGHT
Comments were given on their process and collection validation plans, and on their proposed changes to their sterility testing.
FDA participants: Lori Tull, Sara Karandish, Joydeep Ghosh, Brian Niland
SLCBB participants: Donna Regan, Kathy Fortune, Salem Akul
Purpose of the Telecon: Discuss proposed changes in sterility testing and comment on draft validation plans.
SLCBB requested the following changes.
Joydeep Ghosh said that the first two changes were acceptable but that -(b)(4)- should be maintained for 14 days to detect -----------(b)(4)----------- as the sponsor has not validated the proposed --------(b)(4)--------- time using ----------(b)(4)----------. He also requested that they submit an amendment containing these changes for formal review.
Next Brent McCright went over the following comments pertaining to their process validation that was submitted for comment by email 7/6/2012.
Comments for process validation
1) For validation, you need to use a manufacturing process that addresses the concerns raised during the inspection. Therefore, before you begin to collect validation data, you need to establish new SOPs that address the 483 observations raised during inspection. I recommend discussion of these changes with Nancy Waites.
SLCBB response: They stated that there have been discussions with Nancy Waites about processing changes.
FDA: Brent McCright recommended that these SOP changes should be submitted for review and approval prior to the collection of validation data.
2) To get an accurate evaluation of your process, you should collect pre and post-processing data on more than 3 samples. A defined time period where you would expect to process 20 – 30 CBUs would be appropriate.
3) Measurement of the recovery of viable CD34+ cells should be added to your evaluation criteria for the PrepaCyte manufacturing process.
SLCBB response: They wanted to only to use 3 CBUs for process validation and did not want to include CD34+ cell analysis.
FDA: Brent McCright told them that CD34+ cell analysis is recommended in the Cord Blood Guidance, and that to demonstrate the manufacturing process as designed is capable of producing reproducible products more than 3 units will be required.
4) To validate the freeze-thaw-reconstitution process, you should then select 3 consecutively processed lots and reconstitute and test for TNC recovery, viable CD34+ cell recovery, viability, and sterility.
SLCBB response: They did not want to do this. They felt they had already submitted similar data.
FDA: Brent McCright responded that since they retrospectively selected the prior units, and used a different process than the one they are going to use, they needed to redo this.
5) Similar data needs to be collected for the Kansas City manufacturing site.
SLCBB response: They realize this.
Next Safa Karandish went over the following comments pertaining to their collection validation that was submitted for comment by email 7/6/2012.
Comments for collection validation
1) Collection validation may be completed with less than ----------(b)(4)-------------- collected units. We recommend that you combine the collection and the process validation using units collected in a defined time period.
SLCBB response: This was only about -(b)(4)- worth of units. They may modify to match their processing plan.
2) We suggest that you include the following evaluation parameters for the collected units and define the acceptance criteria for each parameter:
a. Labeling verification
SLCBB response: Labeling is included in “technical errors”
b. Completion and documentation of donor screening and other collection related forms
c. Confirmation of bag integrity
d. % of units with acceptable volume
e. Temperature during transportation of units from the collection sites to the processing facility. As communicated previously, we highly recommend that you implement a method for continuous temperature monitoring during transportation of units (e.g. data logger or min/max thermometers) before conducting the validation.
3) We understand that for quality assurance purposes, you track the storage temperature at the collection sites. Please note that if you define an acceptable storage temperature range for the collection areas in your validation plan, you should not have an acceptable deviation rate.
SLCBB response: They will reconsider this evaluation parameter.
4) You have included sterility monitoring in your proposed validation plan but it is not clear whether the positive sterility acceptance rate is for pre or post-processing.
SLCBB response: Sterility will be done post processing
FDA: Safa Karandish asked for clarification on the temp monitoring during transportation of units from the collection sites. She recommended continuous temperature monitoring rather than only recording temperatures at pick up times.
SLCBB response: They said they would consider it but that during inspection they were told by Nancy Waites that their current procedure was OK. They also stated that the entire trip takes up to -(b)(4)- but they don’t routinely monitor the trip time.
FDA: Safa Karandish reminded the sponsor that the collection validation should be performed at the Kansas facility as well. She also informed them that comments on the draft SOPs submitted in amendment 8 were emailed to SLCBB by Lori Tull on 7/11/12.
SLCBB response: They will review the comments.
FDA: At the end of the telecon Brent McCright requested clarification on their acceptance criteria – does the mean or all samples have to be within 2 standard deviations of the historical mean? He also requested SLCBB submit updated validation plans as an amendment to the BLA.
SLCBB response: They will clarify their acceptance criteria and submit an amendment.