From: Tull, Lori
Sent: Monday, December 05, 2011 9:46 AM
To: 'Donna Regan'
Subject: FDA requests for information
Below is a revised list of our requests for information.
Items 1 ? 5 listed below are needed to file your BLA. Please submit this information by December 12. Item 6 identifies sterility testing information that will be required during the review process.
1. The donor consent and screening, cord blood and maternal specimen collection, donor eligibility determination, cord blood processing, and lot release testing SOPs used at the Kansas City, St. Luke (SLCI) manufacturing facility need to be submitted for review. For processes where the SLCI SOPs are identical to St. Louis (SLCBB) SOPs, this needs to be specifically stated.
2. Please submit a table and/or flowchart that summarizes in process testing performed during manufacturing.
3. Please provide the lot release testing SOPs that are referenced in Figure 19 of your submission - Hemoglobin testing (CB0208.XX), TNC (TE01.XX), Viable Nucleated Cells (TS04.XX), Viable CD34 counts (HV0201.XX), Colony forming assay (GP0304.XX), ABO (TS.07.XX), Initial HLA (CB0203.XX), Confirmatory HLA (CB0203.XX).
4. Validation results from both the SLCBB and the SLCI manufacturing sites should be provided for every assay that is used to determine whether a product can be made for distribution.
For quantitative test methods, the validation studies must demonstrate assay linearity, precision, accuracy, and robustness. For qualitative test methods, the validation studies must demonstrate assay specificity, accuracy, and robustness.
a. We note that you have submitted an assay validation plan for the -----(b)(4)----- sterility testing system, but you also need to submit validation data for both the SLCI and SLCBB sites. You also need to submit the SOPs used for sterility testing at both the SLCI and SLCBB sites.
b. Please submit validation data for TNC and viable CD34+ cell assays for the SLCI Kansas City site. Validation data will be required even if the SLCI site uses the same assays and equipment as the SLCBB site.
c. For ABO Blood typing, and the Colony Forming Assay, please supply a validation plan and data for both the SLCI and SLCBB sites.
d. Please provide validation data for HLA typing, hemoglobin analysis, and infectious disease testing which are performed by outside contractors. Supporting information should include proficiency test results, methods used, and contractor accreditations/certifications.
e. Please submit validation results for collections performed at the SLCI manufacturing sites.
5. Shipping validation data is needed. This data should demonstrate that your cord blood unit does not degrade during shipping to clinical sites. The method/SOP used to ship cord blood units from SLCI to SLCBB also needs to be submitted for review.
6. The following information is needed for the assessment of your sterility testing:
a. Details of the microbial species identification method for the positive culture samples.
b. Information on your ---(b)(4)--- device, including a description of the device and working principle, its location, and serial number. Please also include a summary of device installation qualification (IQ) and operation qualification (OQ) reports.
c. A complete composition of all microbial culture media (used during the actual lot-release sterility assay and during assay validation), their qualification methods, incubation temperature and humidity level used (please indicate the respective tolerance limits), and indicate the qualification test frequency.
d. We note that you have a false-positive category for your sterility test results. Do you include the false-positive samples in your releasable inventory? Do you retest a sterility-positive cord blood unit if you find your sterility test is invalid? If yes, please submit details for the retesting procedure.
Lori A. Tull, RAC
Regulatory Project Manager
Office of Cellular, Tissue, and Gene Therapies
Center for Biologics Evaluation and Research
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