May 30, 2013 Approval Letter - ALLOCORD
Our STN: BL 125413/0
SSM Cardinal Glennon Children's Medical Center
Attention: Ms. Donna M Regan
3662 Park Avenue
St. Louis, MO 63110
Dear Ms. Regan:
We are issuing Department of Health and Human Services U.S. License No. 1873 to SSM Cardinal Glennon Children’s Medical Center, St. Louis, Missouri 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 isan 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 at your facility in St. Louis, Missouri. You may label your product with the proprietary name ALLOCORD and will market it in 35 ml cryobags.
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 36 months from the date of manufacture when stored at ≤ 150° C. The date of manufacture shall be defined as the date the product is cryopreserved. 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.
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.
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. If an infectious disease transmission event is serious and unexpected, you must submit a 15-day “alert report,” as required under 21 CFR 600.80 (c)(1)(i). Infectious disease transmission events that do not meet criteria for expedited submission require periodic reports and must be submitted as individual case reports within 15 days, as authorized under 21 CFR 600.80(c)(2)(i). You should submit reports for all other non-expedited adverse events under the periodic reporting requirements specified in 21 CFR 600.80(c)(2).
AGREED UPON POSTMARKETING COMMITMENTS
We acknowledge your written commitments as described in your letter of May 24, 2013 as outlined below:
Postmarketing Studies not subject to reporting requirements of 21 CFR 601.70.
- You will 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.
- You will submit a 15-day “alert report” for each serious infusion reaction associated with administration of HPC, Cord Blood.
We request that you submit information concerning nonclinical and chemistry, manufacturing, and control postmarketing commitments and final reports to your BLA, STN BL 125413.
Please use the following designators to label prominently all submissions, including supplements, relating to these postmarketing study commitments as appropriate:
- Postmarketing Study Correspondence
- Postmarketing Study Commitment – Final Study Report
- Supplement Contains Postmarketing Study Commitment – Final Study Report
For each postmarketing commitment not subject to the reporting requirements of 21 CFR 601.70, you may report the status to FDA as a “PMC Submission – Status Update.” The status report for each commitment should include:
- The original schedule for the commitment, and
- The status of the commitment (i.e., pending, ongoing, delayed, terminated, or submitted).
When you have fulfilled your commitment, submit your final report as PMC Submission – Final Study Report or Supplement Contains Postmarketing Study Commitment – Final Study Report.
If you have any questions, please contact the Regulatory Project Manager, Lori Tull, at
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Mary A. Malarkey
Office of Compliance and
Center for Biologics
Evaluation and Research
Celia M. Witten, Ph.D., M.D.
Office of Cellular, Tissue and Gene Therapies
Center for Biologics
Evaluation and Research