First fda approval of cb drug

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  • 1. HIGHLIGHTS OF PRESCRIBING INFORMATION The recommended minimum dose is 2.5 x 107 nucleated cells/kg atThese highlights do not include all the information needed to use cryopreservation. (2.1)HEMACORD safely and effectively. See full prescribing information for Do not administer HEMACORD through the same tubing with other productsHEMACORD. except for normal saline. (2.3)HEMACORD (hematopoietic progenitor cells, cord blood) -----------------------DOSAGE FORMS AND STRENGTHS-----------------Injectable Suspension for Intravenous Use Each unit contains a minimum of 5 x 108 total nucleated cells with at least 1.25 xInitial U.S. Approval: XXXX 106 viable CD34+ cells at the time of cryopreservation. The exact pre-cryopreservation nucleated cell content of each unit is provided on the containerWARNING: FATAL INFUSION REACTIONS, GRAFT VERSUS label and accompanying records. (3)HOST DISEASE, ENGRAFTMENT SYNDROME, AND GRAFTFAILURE -----------------------------CONTRAINDICATIONS----------------------------See full prescribing information for complete boxed warning.Known sensitivity to dimethyl sulfoxide (DMSO), Dextran 40 or plasma proteins.(4) Fatal infusion reactions: Monitor patients during infusion anddiscontinue for severe reactions. Use is contraindicated in ------------------------WARNINGS AND PRECAUTIONS-----------------patients with known allergy to dimethyl sulfoxide (DMSO), Allergic Reactions and Anaphylaxis (5.1)Dextran 40 or human serum albumin. (4, 5.1, 5.2) Infusion Reactions (5.2) Graft-vs-host disease (GVHD): GVHD may be fatal. Graft-versus-Host Disease (5.3)Administration of immunosuppressive therapy may decrease the Engraftment Syndrome (5.4)risk of GVHD. (5.3) Graft Failure (5.5) Engraftment syndrome: Engraftment syndrome may be fatal. Malignancies of Donor Origin (5.6)Treat engraftment syndrome promptly with corticosteroids. (5.4) Transmission of Serious Infections (5.7) Transmission of Rare Genetic Diseases (5.8) Graft failure: Graft failure may be fatal. Monitor patients forlaboratory evidence of hematopoietic recovery. (5.5)------------------------------ADVERSE REACTIONS--------------------------Mortality, from all causes, at 100 days post-transplant was 25%. (5, 6.1)-----------------------INDICATIONS AND USAGE------------------------The most common infusion-related adverse reactions (>5%) are hypertension,HEMACORD is an allogeneic cord blood hematopoietic progenitor cell therapyvomiting, nausea, bradycardia, and fever. (6.1)indicated for use in unrelated donor hematopoietic progenitor cell transplantationprocedures in conjunction with an appropriate preparative regimen for To report SUSPECTED ADVERSE REACTIONS, contact the New Yorkhematopoietic and immunologic reconstitution in patients with disorders affecting Blood Center at 1-866-767-NCBP (1-866-767-6227) and FDA at 1-800-FDA-the hematopoietic system that are inherited, acquired, or result from 1088 or www.fda.gov/medwatch.myeloablative treatment. (1)------------------------USE IN SPECIFIC POPULATIONS---------------------The risk benefit assessment for an individual patient depends on the patientPregnancy: Based on animal data, may cause fetal harm. Use only if clearlycharacteristics, including disease, stage, risk factors, and specific manifestationsneeded. (8.1)of the disease, on characteristics of the graft, and on other available treatments ortypes of hematopoietic progenitor cells. (1)See 17 for PATIENT COUNSELING INFORMATION--------------------DOSAGE AND ADMINISTRATION-------------------- Revised: ZZ/ZZZZ Unit selection and administration of HEMACORD should be done under the direction of a physician experienced in hematopoietic progenitor cell transplantation.FULL PRESCRIBING INFORMATION: CONTENTS*WARNING: FATAL INFUSION REACTIONS, GRAFT VERSUS HOST8USE IN SPECIFIC POPULATIONSDISEASE, ENGRAFTMENT SYNDROME, AND GRAFT FAILURE 8.1 Pregnancy1 INDICATIONS AND USAGE8.4 Pediatric Use2 DOSAGE AND ADMINISTRATION8.5 Geriatric Use2.1 Dosing 8.6 Renal Disease2.2 Preparation for Infusion10 OVERDOSAGE2.3 Administration 10.1 Human Overdosage Experience3 DOSAGE FORMS AND STRENGTHS 10.2 Management of Overdose4 CONTRAINDICATIONS 11 DESCRIPTION5 WARNINGS AND PRECAUTIONS12 CLINICAL PHARMACOLOGY5.1 Allergic Reactions and Anaphylaxis 12.1 Mechanism of Action5.2 Infusion Reactions14 CLINICAL STUDIES5.3 Graft versus Host Disease (GVHD)16 HOW SUPPLIED/STORAGE AND HANDLING5.4 Engraftment Syndrome17 PATIENT COUNSELING INFORMATION5.5 Graft Failure5.6 Malignancies of Donor OriginINSTRUCTIONS FOR PREPARATION FOR INFUSION5.7 Transmission of Serious Infection5.8 Transmission of Rare Genetic Diseases6 ADVERSE REACTIONS*Sections or subsections omitted from the full prescribing information are not6.1 Clinical Study Experience listed.1 of 20

2. 1 FULL PRESCRIBING INFORMATION WARNING: FATAL INFUSION REACTIONS, GRAFT VERSUS HOST DISEASE,ENGRAFTMENT SYNDROME AND GRAFT FAILURE Fatal infusion reactions: HEMACORD administration can result in serious, including fatal, infusion reactions. Monitor patients and discontinue HEMACORD infusion for severe reactions. Use is contraindicated in patients with known allergy to dimethyl sulfoxide (DMSO), Dextran 40 or human serum albumin. [See Contraindications (4) and Warnings and Precautions (5.1, 5.2)] Graft-vs-host disease (GVHD): GVHD is expected after administration of HEMACORD, and may be fatal. Administration of immunosuppressive therapy may decrease the risk of GVHD. [See Warnings and Precautions (5.3)] Engraftment syndrome: Engraftment syndrome may progress to multiorgan failure and death. Treat engraftment syndrome promptly with corticosteroids. [See Warnings and Precautions (5.4)] Graft failure: Graft failure may be fatal. Monitor patients for laboratory evidence of hematopoietic recovery. Prior to choosing a specific unit of HEMACORD, consider testing for HLA antibodies to identify patients who are alloimmunized. [See Warnings and Precautions (5.5)] 2 3 1 INDICATIONS AND USAGE 4 5 HEMACORD is an allogeneic cord blood hematopoietic progenitor cell therapy indicated for use 6 in unrelated donor hematopoietic progenitor stem cell transplantation procedures in conjunction 7 with an appropriate preparative regimen for hematopoietic and immunologic reconstitution in 8 patients with disorders affecting the hematopoietic system that are inherited, acquired, or result 9 from myeloablative treatment.1011 The risk benefit assessment for an individual patient depends on the patient characteristics,12 including disease, stage, risk factors, and specific manifestations of the disease, on characteristics13 of the graft, and on other available treatments or types of hematopoietic progenitor cells.1415 2 DOSAGE AND ADMINISTRATION1617 For intravenous use only.18 Do not irradiate.1920 2.1 Dosing2122 The recommended minimum dose is 2.5 x 107 nucleated cells/kg at cryopreservation. Multiple23 units may be required in order to achieve the appropriate dose.2425 Matching for at least 4 of 6 HLA-A antigens, HLA-B antigens, and HLA-DRB1 alleles is26 recommended. The HLA typing and nucleated cell content for each individual unit of27 HEMACORD are documented on the container label and/or in accompanying records.28 2 of 20 3. 29 2.2 Preparation for Infusion3031 HEMACORD should be prepared by a trained healthcare professional.3233 Do not irradiate HEMACORD.34 See the appended detailed instructions for preparation of HEMACORD for infusion.35 Once prepared for infusion, HEMACORD may be stored at 4 to 25C for up to 4 hours if36 DMSO is not removed, and at 4C for up to 24 hours if DMSO is removed in a washing37 procedure.38 The recommended limit on DMSO administration is 1 gram per kg body weight per day. [See39 Warnings and Precautions (5.2)]4041 2.3 Administration4243 HEMACORD should be administered under the supervision of a qualified healthcare44 professional experienced in hematopoietic progenitor cell transplantation.4546 1. Confirm the identity of the patient for the specified unit of HEMACORD prior to47administration.48 2. Confirm that emergency medications are available for use in the immediate area.49 3. Ensure the patient is hydrated adequately.50 4. Premedicate the patient 30 to 60 minutes before the administration of HEMACORD.51Premedications can include any or all of the following: antipyretic, histamine blocker,52and corticosteroids.53 5. Inspect the product for any abnormalities such as unusual particulates and for breaches54of container integrity prior to administration. Prior to infusion, discuss all such product55irregularities with the laboratory issuing the product for infusion.56 6. Administer HEMACORD by intravenous infusion. Do not administer in the same57tubing concurrently with products other than 0.9% Sodium Chloride, Injection (USP).58HEMACORD may be filtered through a 170 to 260 micron filter designed to remove59clots. Do NOT use a filter designed to remove leukocytes.60 7. For adults, begin infusion of HEMACORD at 100 milliliters per hour and increase the61rate as tolerated. For children, begin infusion of HEMACORD at 1 milliliter per kg per62hour and increase as tolerated. The infusion rate should be reduced if the fluid load is63not tolerated. The infusion should be discontinued in the event of an allergic reaction64or if the patient develops a moderate to severe infusion reaction. [See Warnings and65Precautions (5) and Adverse Reactions (6)]66 8. Monitor the patient for adverse reactions during, and for at least six hours after,67administration. Because HEMACORD contains lysed red cells that may cause renal68failure, careful monitoring of urine output is also recommended.6970 3 DOSAGE FORMS AND STRENGTHS7172 Each unit of HEMACORD contains a minimum of 5.0 x 108 total nucleated cells with a73 minimum of 1.25 x 106 viable CD34+ cells, suspended in 10% dimethyl sulfoxide (DMSO) and74 1% Dextran 40, at the time of cryopreservation.7576 The exact pre-cryopreservation nucleated cell content is provided on the container label and in77 accompanying records.78 3 of 20 4. 79 4 CONTRAINDICATIONS 80 81 HEMACORD is contraindicated in patients with known hypersensitivity to dimethyl sulfoxide 82 (DMSO), Dextran 40 or plasma proteins. [See Description (11) and Dosage and Administration 83 (2.2)] 84 85 5 WARNINGS AND PRECAUTIONS 86 87 5.1 Allergic Reactions and Anaphylaxis 88 89 Allergic reactions may occur with infusion of hematopoietic progenitor cells, cord blood 90 (HPC-C), including HEMACORD. Reactions include bronchospasm, wheezing, angioedema, 91 pruritus and hives [see Adverse Reactions (6)]. Serious hypersensitivity reactions, including 92 anaphylaxis, also have been reported. These reactions may be due to dimethyl sulfoxide 93 (DMSO), Dextran 40, or a plasma component of HEMACORD. 94 95 5.2 Infusion Reactions 96 97 Infusion reactions are expected to occur and include nausea, vomiting, fever, rigors or chills, 98 flushing, dyspnea, hypoxemia, chest tightness, hypertension, tachycardia, bradycardia, 99 dysgeusia, hematuria, and mild headache. Premedication with antipyretic, histamine antagonists,100 and corticosteroids may reduce the incidence and intensity of infusion reactions.101102 Severe reactions, including respiratory distress, severe bronchospasm, severe bradycardia with103 heart block or other arrhythmias, cardiac arrest, hypotension, hemolysis, elevated liver enzymes,104 renal compromise, encephalopathy, loss of consciousness, and seizure also may occur. Many of105 these reactions are related to the amount of DMSO administered. Minimizing the amount of106 DMSO administered may reduce the risk of such reactions, although idiosyncratic responses may107 occur even at DMSO doses thought to be tolerated. The actual amount of DMSO depends on the108 method of preparation of the product for infusion. Limiting the amount of DMSO infused to no109 more than 1 gm/kg/day is recommended. [See Overdosage (10)]110111 If infusing more than one unit of HPC-C on the same day, do not administer subsequent units112 until all signs and symptoms of infusion reactions from the prior unit have resolved.113114 Infusion reactions may begin within minutes of the start of infusion of HEMACORD, although115 symptoms may continue to intensify and not peak for several hours after completion of the116 infusion. Monitor the patient closely during this period. When a reaction occurs, discontinue the117 infusion and institute supportive care as needed.118119 5.3 Graft-versus-Host Disease (GVHD)120121 Acute and chronic GVHD may occur in patients who have received HEMACORD. Classic122 acute GVHD is manifested as fever, rash, elevated bilirubin and liver enzymes, and diarrhea.123 Patients transplanted with HEMACORD also should receive immunosuppressive drugs to124 decrease the risk of GVHD. [See Adverse Reactions (6.1)]125126 5.4 Engraftment Syndrome127128 Engraftment syndrome is manifested as unexplained fever and rash in the peri-engraftment129 period. Patients with engraftment syndrome also may have unexplained weight gain,4 of 20 5. 130 hypoxemia, and pulmonary infiltrates in the absence of fluid overload or cardiac disease. If131 untreated, engraftment syndrome may progress to multiorgan failure and death. Begin treatment132 with corticosteroids once engraftment syndrome is recognized in order to ameliorate the133 symptoms. [See Adverse Reactions (6.1)]134135 5.5 Graft Failure136137 Primary graft failure, which may be fatal, is defined as failure to achieve an absolute neutrophil138 count greater than 500/uL blood by Day 42 after transplantation. Immunologic rejection is the139 primary cause of graft failure. Patients should be monitored for laboratory evidence of140 hematopoietic recovery. Consider testing for HLA antibodies in order to identify patients who141 are alloimmunized prior to transplantation and to assist with choosing a unit with a suitable HLA142 type for the individual patient. [See Adverse Reactions (6.1)]143144 5.6 Malignancies of Donor Origin145146 Patients who have undergone HPC-C transplantation may develop post-transplant147 lymphoproliferative disorder (PTLD), manifested as a lymphoma-like disease favoring non-148 nodal sites. PTLD is usually fatal if not treated.149150 The incidence of PTLD appears to be higher in patients who have received antithymocyte151 globulin. The etiology is thought to be donor lymphoid cells transformed by Epstein-Barr virus152 (EBV). Serial monitoring of blood for EBV DNA may be warranted in high-risk groups.153154 Leukemia of donor origin also has been reported in HPC-C recipients. The natural history is155 presumed to be the same as that for de novo leukemia.156157 5.7 Transmission of Serious Infections158159 Transmission of infectious disease may occur because HEMACORD is derived from human160 blood. Disease may be caused by known or unknown infectious agents. Donors are screened for161 increased risk of infection with human immunodeficiency virus (HIV), human T-cell162 lymphotropic virus (HT...