Vaccines, Blood & Biologics
Record of Telephone Conversation, November 16, 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: 16-Nov-2012 09:30 AM Initiated by FDA? Yes
Telephone Number: ----------------(b)(4)--------------------------
1. Inspection Related
2. Information Request
Author: CANDACE JARVIS
LIfe South requested a teleconference with FDA to request additional clarification of the batch record requirements, growth promotion (483), the freeze curve) and their ---(b)(4)------- validation protocol.
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)
Non-FDA Participants: Jill Evans, (Vice President of Quality)
Amy Lambert, (Manager Cellular Therapies)
Tammy Lawson, (Validation Coordinator)
Lori Masingil, (Technical Communications Manager)
Juan Merayo-Rodriguez, (Medical Director)
Ed Downey, (Administrative Laboratory Manager)
Trans-BLA Group: No
Related STNs: None
Related PMCs: None
LifeSouth requested a teleconference with FDA on November 13, 2012 to obtain additional clarification of the batch records, growth promotion testing, the freeze curve, and their ---(b)(4)--- validation protocol.
Draft Batch records: Draft sent via email on 11/15/12 (see attachment)
FDA acknowledge receipt of the draft that was sent on 11/15 and stated that it looks that they could submit formally; however, there were some suggestions that were given regarding section 7. FDA asked that they describe HES by providing the complete name. FDA also stated that they need to provide the “rest” period start and end time for this step. FDA further stated that they need to describe each step or cross reference the associated SOP in each section. The sponsor agreed.
With regard to the timing of DMSO, the sponsor stated that they had two options for this: 1) Cryopreserve units at different time intervals after DMSO addition and determine post thaw viability of each unit or 2) After addition of DMSO, sample from a unit at different time intervals and determine the post thaw viability of each sample. FDA stated that both approaches are acceptable. The sponsor agreed.
Life south wanted to reverify if it would be OK to use the ----------(b)(4)-------------------------------- for the sterility test as it would not test for the DMSO added to the final product. FDA confirmed that it would be OK in this case because the sponsor will be adding sterile DMSO to the final product and under aseptic conditions. FDA also recommended the sponsor to keep the ratio of plasma and RBC in the by-product test sample constant during their assay validation and continue using the validated ratio for actual product testing after the approval of the BLA.
Growth Promotion (draft protocol sent via email11/13 (attached)
FDA indicated that the proposal submitted is not fully acceptable. FDA reiterated from the last meeting that identifying facility organisms should be included in a separate protocol for environmental monitoring and not in the growth promotion testing protocol. FDA further clarified that qualifying facility organisms should be a part of the environmental monitoring program and that growth promotion testing is used to support media for media fills and environmental monitoring media. The firm’s environmental monitoring program should include qualification of facility organisms, trending results collected over time etc.. FDA also indicated that requalification of the cleanroom should occur after renovations. The sponsor agreed and noted that they will perform requalification after remodeling
FDA indicated that equipment qualification of new incubators should not be included in the growth promotion protocol. This should be a separate and under equipment qualification. The sponsor agreed.
LifeSouth will resubmit a revised protocol for review for growth promotion testing.
The sponsor referred to the July 16, 2012 FDA letter and asked for further clarification on the detailed validation results for the freeze curve. FDA stated that the LifeSouth should provide a high degree of assurance that the ---(b)(4)------ instrument and condition used for cryopreservation works reproducibly. The sponsor stated that they provided the cryopreservation study. FDA agreed, but again reiterated that they needed more detailed information on the validation of cryopreservation (for example the exact freezing conditions and asked that they submit this information as well as the freeze curve for each sample tested. The sponsor agreed.
Timelines- the sponsor stated that they will be provided a calendar detailing the proposed timelines as to when FDA should expect responses to outstanding issues and their facility changes.
Flooring-FDA noted that they have further reviewed the information provided in the 483 response regarding the flooring in attachment 4 and reiterated that it is up to LifeSouth to install the proper flooring for their cleanroom. FDA indicated that information in Attachment 4 states that the flooring is classified as “Light Industrial Cleanroom.” The sponsor should check to make sure this is equivalent to GMP manufacturing flooring material and that it can withstand caustic cleaning agents. The sponsor assured FDA that they were aware of this and that the contractor recommended the flooring choice.
Life south asked FDA if it was ok that they submit the data collection after the cleanroom installation during the first or second week of January. FDA asked that they keep them informed of the timelines. The sponsor agreed.
11 pages redacted due to (b)(4)