Status: approved by FDA in Nov. 2011

Organizations involved:

New York Blood Center, Inc. – Manuf.; R&D; Tech.; U.S. mark.

Description: Hemacord is an allogeneic cord blood hematopoietic progenitor cell therapy. Hemacord consists of hematopoietic progenitor cells, monocytes, lymphocytes, and granulocytes from human cord blood. Blood recovered from umbilical cord and placenta is volume reduced and partially depleted of red blood cells and plasma. The active agent is hematopoietic progenitor cells which express the cell surface marker CD34. The potency of cord blood is determined by measuring the numbers of total nucleated cells (TNC) and CD34+ cells, and cell viability. Each unit of Hemacord contains a minimum of 5 x 10.sup.8 total nucleated cells with at least 1.25 x 10.sup.6 viable CD34+ cells at the time of cryopreservation. The cellular composition of Hemacord depends on the composition of cells in the blood recovered from the umbilical cord and placenta of the donor.

Hemacord is supplied as a cryopreserved cell suspension in a sealed bag containing a minimum of 5 x 10.sup.8 total nucleated cells with a minimum of 1.25 x 106 viable CD34+ cells in a volume of 25 milliliters. The actual nucleated cell count, the CD34+ cell count, the ABO group, and the HLA typing are listed on the container label and/or accompanying records sent with each individual unit.

Cord blood is collected from mothers who screen and test negative for the relevant infectious disease markers. The cord blood is processed by volume reduction and partial red cell and plasma depletion using the Thermogenesis AXP automated system. The final product is in a 25 ml total volume containing 10% DMSO and 1% Dextran 40. Each unit is frozen using a controlled rate freezing process and then stored in liquid nitrogen (-196˚C). The final product is tested for purity, identity, sterility, and potency. Hemacord is cryopreserved in two-compartment freezing bags. The larger compartment contains 80% of the cell suspension (20 ml) and the smaller contains 20% (5 ml). The cryobag is placed and maintained inside a protective metal canister for freezing and storage in liquid nitrogen in the BioArchive System (Thermogenesis).

Approved by FDA for allogeneic hematopoietic (blood-forming) stem cell transplantation, Hemacord is the first approval of a stem cell product in the world, the the first approval of a therapeutic made from human umbilical cord blood.

Biological.: Placental/umbilical cord blood (HPC-C), like bone marrow and peripheral blood, is rich in hematopoietic progenitor cells, and has long been used in the treatment of a variety of disorders, including hematologic malignancies, metabolic disorders, and immunodeficiencies. contains hematopoietic progenitor cells (HPCs) from human cord blood.

Cord blood is one of three sources of HPCs used in transplants; the other two are bone marrow and peripheral blood. Once these HPCs are infused into patients, the cells migrate to the bone marrow where they divide and mature. When the mature cells move into the bloodstream they can partially or fully restore the number and function of many blood cells, including immune function.

The product includes residual traces of dimethyl sulfoxide (DMSO) and Dextran 40.

Nomenclature: stem cord cells [BIO]; Hemacord [TR US]

Hematopoietic progenitor cells-cord (HPC-C) cell therapy [FDA]; cord blood stem cells [SY]; HPC-C [SY]; NDC 76489-001-01 [NDC]

Biological.: Hematopoietic stem/progenitor cells from HPC-C migrate to the bone marrow where they divide and mature. The mature cells are released into the bloodstream, where some circulate and others migrate to tissue sites, partially or fully restoring blood counts and function, including immune function, of blood-borne cells of marrow origin. In patients with enzymatic abnormalities due to certain severe types of storage disorders, mature leukocytes resulting from HPC-C transplantation may synthesize enzymes that may be able to circulate and improve cellular functions of some native tissues. However, the precise mechanism of action is unknown.

Companies.: The product was developed and is manufactured by the New York Blood Center, Inc., CBER/FDA est. no. 0465. Prior to the BLA submission, NYBC had moved its entire manufacturing and storage resources to a state-of-the-art facility in Long Island City, NY.

FDA class: Biologic BLA

Approvals: Date = 20111110, full BLA

Indications: [full text of the "Indications and USAGE" of the product insert/labeling}:

Hemacord is an allogeneic cord blood hematopoietic progenitor cell therapy indicated for use in unrelated donor hematopoietic progenitor stem 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.

Status: Since 1996, the NYBC's National Cord Blood Program (NCBP), Howard P. Milstein National Cord Blood Center, had provided cord blood units for transplantation under an Investigational New Drug (IND) exemption from the FDA. The mission of the NCBP is to facilitate access to cord blood as a treatment option for patients, notably those from diverse ethnic backgrounds. NCBP was the first established umbilical cord blood bank to collect, process, test and store cord blood units and make them available for transplantation to patients in need of hematopoietic stem cell transplantation. Approval did not include orphan designation.

In an Oct. 2009 Federal Register notice, "Guidance for Industry: Minimally Manipulated, Unrelated Allogeneic Placental/Umbilical Cord Blood Intended for Hematopoietic Reconstitution for Specified indications:," FDA announced that manufacturers of cord blood would be required to have an approved BLA or IND in effect for unrelated cord blood shipped after Oct. 20, 2011.

To obtain FDA approval, all collection and manufacturing conditions of the cord blood units had to meet FDA standards for product potency, purity and efficacy, and patient safety. NCBP's Biologics License Application (BLA) included extensive documentation of the systems and controls used, and the validations performed to ensure compliance with FDA standards in all steps of manufacturing (collections, processing, testing, typing, cryopreservation, storage, distribution and shipping) cord blood units for clinical use. Further, the BLA included the safety data from the transplantation of more than 4,000 cord blood grafts.

In Nov. 2011, FDA approval was granted. Time from submission to approval was 10 months. But Cord blood products are not subject to PDUFA. Despite this, FDA assigns and adheres to PDUFA schedules during review of BLAs for these products.

To assist manufacturers in applying for approval of certain cord blood products, FDA issued a 2009 guidance document that explained how to obtain approval, and created a Cord Blood Licensure Workshop website. FDA also permitted manufacturers to rely primarily on published literature to establish safety and effectiveness.

Trials: The effectiveness of HPC-C, as defined by hematopoietic reconstitution, was demonstrated in one single-arm prospective study, and in retrospective reviews of data from an observational database for Hemacord and data in the dockets and public information. Sixty-six percent (n=862) of the 1299 patients in the docket and public data underwent transplantation as treatment for hematologic malignancy.

Medical: The recommended minimum dose is 2.5 x 10.sup.7 nucleated cells/kg at cryopreservation administered intravenously. Multiple units may be required in order to achieve the appropriate dose. Matching for at least 4 of 6 HLA-A antigens, HLA-B antigens, and HLA-DRB1 alleles is recommended. The HLA typing and nucleated cell content for each individual unit of Hemacord are documented on the container label and/or in accompanying records.

The "disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment" for which Hemacord is approved include patients with hematologic malignancies, primary immunodeficiency diseases, bone marrow failure, and beta-thalassemia. Hemacord cells can be used for unrelated hematopoietic progenitor cell transplantation procedures in patients with inherited and acquired disorders affecting the hematopoietic system, and those resulting from myeloablative therapy.

Hmeacord has a boxed warning regarding the risks of Graft Versus Host Disease (GVHD), engraftment syndrome, graft failure, and infusion reactions, each of which may be fatal. Patients who receive Hemacord should be monitored carefully. A risk benefit assessment, unit selection and administration of Hemacord should be done under the direction of a physician experienced in hematopoietic stem cell transplantation.

Market: The market for Hemacord currently appears tobe be rather small, apparently only 1,000s of procedures annually. However, this could increase greatly as hematopietic stem cells are adopted for indications: including recovery from myeloablative, e.g., chemotherapy, treatments.