October 4, 2012 Approval Letter - Ducord
Our STN: BL 125407/0
Duke University School of Medicine
Translational Cell Therapy Center
Attention: Bruce Burnett, Ph.D.
Carolinas Cord Blood Bank
Hock Plaza, 2424 Erwin Road, Suite 402
Durham, NC 27705
Dear Dr. Burnett:
We are issuing Department of Health and Human Services U.S. License No. 1870 to Duke University School of Medicine, Durham, NC, under the provisions of section 351(a) of the Public Health Service Act controlling the manufacture and sale of biological products. The license authorizes you to introduce or deliver for introduction into interstate commerce HPC, Cord Blood manufactured from the date of this authorization forward.
Under this license, you are authorized to manufacture the product HPC, Cord Blood. HPC, Cord Blood is an allogeneic cord blood hematopoietic progenitor cell therapy indicated for use in unrelated donor hematopoietic progenitor cell transplantation procedures in conjunction with an appropriate preparative regimen for hematopoietic and immunologic reconstitution in patients with disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment. The risk benefit assessment for an individual patient depends on the patient characteristics, including disease, stage, risk factors, and specific manifestations of the disease, on characteristics of the graft, and on other available treatments or types of hematopoietic progenitor cells.
Under this license, you are approved to manufacture HPC, Cord Blood prepared at your facility, in Durham, NC. You may label your product with the proprietary name DUCORD and will market it in cryobags containing 25 milliliters.
We did not refer your application to the Cellular, Tissue, and Gene Therapy Advisory Committee because our review of information submitted in your BLA did not raise concerns or controversial issues which would have benefited from an advisory committee discussion.
The dating period for HPC, Cord Blood shall be 84 months from the date of manufacture when stored at ≤ -150°C. The date of manufacture shall be defined as the date of cryopreservation. We have approved the stability protocol in your license application for the purpose of extending the expiration dating period of HPC, Cord Blood under 21 CFR 601.12.
You currently are not required to submit samples of future lots of HPC, Cord Blood to the Center for Biologics Evaluation and Research (CBER) for release by the Director, CBER, under 21 CFR 610.2. We will continue to monitor compliance with 21 CFR 610.1 requiring completion of tests for conformity with standards applicable to each product prior to release of each lot.
You must submit information to your biologics license application for our review and written approval under 21 CFR 601.12 for any changes in, including but not limited to, the manufacturing, testing, packaging or labeling of HPC, Cord Blood, or in the manufacturing facilities.
You must submit reports of biological product deviations under 21 CFR 600.14. You should identify and investigate all manufacturing deviations promptly, including those associated with processing, testing, packing, labeling, storage, holding and distribution. If the deviation involves a distributed product, may affect the safety, purity, or potency of the product, and meets the other criteria in the regulation, you must submit a report on Form FDA-3486 to the Director, Office of Compliance and Biologics Quality, Center for Biologics Evaluation and Research, HFM-600, 1401 Rockville Pike, Rockville, MD 20852-1448.
Please provide your final content of labeling in Structured Product Labeling (SPL) format and include the carton and container labels. In addition, please submit three original paper copies for carton and container final printed labeling. All final labeling should be submitted as Product Correspondence to this BLA at the time of use (prior to marketing) and include implementation information on FDA Form 356h.
In addition, please submit the final content of labeling (21 CFR 601.14) in SPL format via the FDA automated drug registration and listing system, (eLIST), as described at http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/default.htm. Information on submitting SPL files using eLIST may be found in the guidance for industry titled, “SPL Standard for Content of Labeling Technical Qs and As at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM072392.pdf.
You may submit two draft copies of the proposed introductory advertising and promotional labeling with an FDA Form 2253 to the Center for Biologics Evaluation and Research, Advertising and Promotional Labeling Branch, HFM-602, 1401 Rockville Pike, Rockville, MD 20852-1448. You must submit copies of your final advertisement and promotional labeling at the time of initial dissemination or publication, accompanied by Form FDA 2253 (21 CFR 601.12(f)(4)).
All promotional claims must be consistent with and not contrary to approved labeling. You should not make a comparative promotional claim or claim of superiority over other products unless you have substantial evidence or substantial clinical experience to support such claims (21 CFR 202.1(e)(6)).
ADVERSE EVENT REPORTING
You must submit adverse experience reports in accordance with the adverse experience reporting requirements for licensed biological products (21 CFR 600.80) and you must submit distribution reports as described in 21 CFR 600.81. You should submit postmarketing adverse experience reports and distribution reports to the Center for Biologics Evaluation and Research, Office of Biostatistics and Epidemiology HFM-210, Food and Drug Administration, 1401 Rockville Pike, Suite 200N, Rockville, MD 20852-1448. Prominently identify all adverse experience reports as described in 21 CFR 600.80. Per 21 CFR 600.2(f), please refer to http://www.fda.gov/AboutFDA/CentersOffices/CBER/ucm106001.htm for updated mailing address information.
In addition, you must submit adverse event reports for any infectious disease transmission within 15 days after learning of the event. Infectious disease transmission refers to an adverse event that involves suspected or confirmed transmission of an infectious agent, whether the recipient develops the infectious disease or only has serologic or other evidence.
FDA regulations require Quarterly Periodic Adverse Experience Reports (PAERS) to contain a narrative summary and analysis of the information in the report and an analysis of the 15-day Alert reports submitted during the reporting interval (21 CFR 600.80(c)2). The narrative summary in PAERs for HPC, Cord Blood should include a detailed summary and assessment of all serious infusion reactions observed during the reporting period, as well as your assessment of each case and the overall frequency of serious infusion reactions since approval and during the reporting period. PAERs should also include any adverse event (e.g., infusion reaction or other adverse event) information forwarded to you from the Stem Cell Therapeutics Outcomes Database (SCTOD) during the reporting period. PAERs should also include the number of units released for infusion and the number of patients receiving infusions with HPC, Cord Blood during the reporting period.
In addition, we acknowledge receipt of your September 20, 2012 letter in which you have agreed to do the following:
- Implement a safety outcomes monitoring and analysis plan. This plan will include a) maintenance of an observational database to include, for all HPC, Cord Blood units released, information including but not limited to, time to neutrophil recovery, graft failure, survival, cause of death, infusion reactions, and other adverse experiences, and b) aggregate analyses of interval and cumulative adverse experience reports, and c) safety outcomes analyses of interval and cumulative data that address early mortality, graft failure-related mortality, graft failure, time to neutrophil recovery, infusion-related events, and other adverse experiences. Reports will include a description of the population analyzed, results of the analyses, whether outcomes indicators were triggered and, if so, what actions were implemented as a result.
- Submit a 15-day “alert report” for each serious infusion reaction associated with administration of HPC, Cord Blood.
If you have any questions, please contact the Regulatory Project Manager, Mark L. Davidson, at (301) 827-6536.
Mary Malarkey Celia M. Witten, Ph.D., M.D.
Office of Compliance and Biologics Quality Office of Cellular, Tissue, and Gene Therapies
Center for Biologics Evaluation and Research Center for Biologics Evaluation and Research
Enclosures: Package Insert, Carton and Container Labels