Method of Viral Depletion or Inactivation. 1. Solvent/detergent. (TNBP/polysorbate 80) 1. Immunoaffinity chromatography. 2.

Transcription

1 TABLE I. PRODUCTS LICENSED IN THE U.S. TO TREAT HEMOPHILIA A A. Recombinant FACTOR VIII Concentrates Product Name Manufacturer Generation Human or Animal Plasma- Derived Protein Used in Culture Medium Method of Viral Depletion or Advate Baxter Third None 1. Immunoaffinity 2. Solvent/detergent Helixate FS Bayer (distributed by CSL Behring) Second Human Plasma Protein Solution Kogenate FS Bayer Second Human Plasma Protein Solution Recombinate Baxter First Bovine Serum Albumin Xyntha Pfizer Third None (B-domain deleted) (TNBP/polysorbate 80) 1. Immunoaffinity 2. Solvent/detergent (TNBP/polysorbate 80) 1. Immunoaffinity 2. Solvent/detergent (TNBP/polysorbate 80) 1. Immunoaffinity 1. Solvent/detergent (TNBP/polysorbate 80) 2. Nanofiltration Stabilizers In Final Vial Heparin in Final Vial Specific Activity of Final Product (IU factor VIII /mg total protein after addition of stabilizer) Trehalose None 4,000-10,000 Sucrose, 28 mg/vial Sucrose, 28 mg/vial Human albumin Sucrose Polysorbate 80 None 4000 None 4000 None None 5,500-9,900 18

2 TABLE I. PRODUCTS LICENSED IN THE U.S TO TREAT HEMOPHILIA A (Continued) B. Prolonged half-life Recombinant FACTOR VIII Concentrate Note that this product has been genetically modified to have a longer half life than standard recombinant FVIII concentrates. Please see Prescribing Information for dosage recommendations. Product Name Manufacturer Mechanism of Prolonged Half-life ELOCTATE Biogen Idec Fc Fusion Protein Generation Third (BDDrFVIIIFc) Human or Animal Plasma-Derived Protein Used in Culture Medium Method of Viral Depletion or None 1. Detergent Triton X Nanofiltration, 15 nm Stabilizers In Final Vial Sucrose Polysorbate 20 Heparin in Final Vial None 19

3 TABLE I. PRODUCTS LICENSED IN THE U.S. TO TREAT HEMOPHILIA A(Continued) C. Human Plasma-Derived ImmunoaffinityPurified FACTOR VIII Concentrates Product Name Manufacturer Method of Viral Hemofil M* Baxter 1. Immunoaffinity 2. Solvent/detergent (TNBP/Octoxynol 9) Hemofil M* Baxter 1. Immunoaffinity 2. Solvent/detergent (TNBP/Octoxynol 9) 3. Nanofiltration, 20 nm Monoclate-P CSL Behring 1. Immunoaffinity 2. Pasteurization (60 o C, 10h) Heparin in Final Vial Specific Activity of Final Product (IU factor VIII/mg total protein after addition of stabilizer) None 2-20 None 2-20 None 5-10 *Hemofil M with nanofiltration was introduced into the US market on September 17, The last lot of Hemofil M without nanofiltration will expire on January 3,

4 TABLE I. PRODUCTS LICENSED IN THE U.S. TO TREAT HEMOPHILIA A (Continued) D. Human Plasma-Derived Intermediate Purity Concentrates That Contain FACTOR VIII and VON WILLEBRAND FACTOR Product Name Manufacturer Method of Viral Alphanate Grifols 1. Affinity 2. Solvent/detergent (TNBP/polysorbate 80) 3. Dry heat (80 o C, 72h) Humate-P Koate-DVI CSL Behring GmbH (Marberg, Germany) Grifols (distributed by Kedrion Biopharma) 1. Pasteurization (60 o C, 10 hrs) 1. Solvent/detergent (TNBP/polysorbate 80) 2. Dry heat (80 o C, 72h) Heparin in Final Vial (units/ml) < None 1-2 None 9-22 SpecificActivity of Final Product (IU FVIII /mg total protein after addition of stabilizer) 21

5 TABLE I. PRODUCTS LICENSED IN THE U.S. TO TREAT HEMOPHILIA A (continued) E. Desmopressin Formulations To Treat MILD HEMOPHILIA A Product Name Manufacturer U.S. Distributor Formulation Recommended Dosage and Administration DDAVP Injection Stimate Nasal Spray for Bleeding Ferring AB (Malmo, Sweden) Ferring AB (Malmo, Sweden) Aventis Pharma CSL Behring For parenteral use (IV or SQ), 4 mcg/ml in a 10-ml vial Nasal spray, l.5 mg/ml. The metered dose pump delivers 0.1 ml (150 mcg) per actuation. The bottle contains 2.5 ml with spray pump capable of delivering mcg doses or mcg doses. 1) 0.3 mcg/kg, mixed in 30 ml normal saline solution, infused I.V. slowly over 30 minutes. May repeat after 24 hours. 2) 0.3 mcg/kg by subcutaneous injection. May repeat after 24 hours. DO NOT USE IN CHILDREN UNDER THE AGE OF 2 YEARS. USE WITH CAUTION IN PREGNANT WOMEN DURING LABOR AND DELIVERY. In patients weighing 50 kg, give one spray in one nostril (dose = 150 mcg). In those weighing 50 kg, give one spray in each nostril (dose = 300 mcg). May repeat after 24 hours. DO NOT USE IN CHILDREN UNDER THE AGE OF 2 YEARS. USE WITH CAUTION IN PREGNANT WOMEN DURING LABOR AND DELIVERY. 22

6 TABLE II. PRODUCTS LICENSED IN THE U.S. TO TREAT HEMOPHILIA B A. Recombinant FACTOR IX Concentrate Product Name Manufacturer Generation Human or Animal Plasma-Derived Protein Used in Culture Medium Method of Viral Depletion or BeneFIX Pfizer Third None 1. Affinity 2. Nanofiltration, 35 nm Rixubis Baxter Third None 1. Solvent-detergent 2. Nanofiltration, 15 nm Stabilizers In Final Vial Sucrose Polysorbate 80 Heparin in Final Vial Specific Activity (IU factor IX/mg total protein) None Sucrose None >200 23

7 TABLE II. PRODUCTS LICENSED IN THE U.S TO TREAT HEMOPHILIA B (Continued) B. Prolonged half-life Recombinant FACTOR IX Concentrate Note that this product has been genetically modified to have a longer half life than standard recombinant FVIII concentrates. Please see Prescribing Information for dosage recommendations. Product Name Manufacturer Mechanism of Prolonged Half-life ALPROLIX Biogen Idec Fc Fusion Protein Generation Human or Animal Plasma-Derived Protein Used in Culture Medium Method of Viral Depletion or Third None 1. Affinity 2. Nanofiltration, 15 nm Stabilizers In Final Vial Sucrose Polysorbate 20 Heparin in Final Vial None 24

8 TABLE II. PRODUCTS LICENSED IN THE U.S TO TREAT HEMOPHILIA B (Continued) C. Human Plasma-Derived Coagulation FACTOR IX Concentrates Product Name Manufacturer Method of Viral Depletion or AlphaNine SD Grifols 1. Dual affinity 2. Solvent/detergent (TNBP/polysorbate 80) 3. Nanofiltration <70kDa Mononine CSL Behring 1. Immunoaffinity 2. Sodium thiocyanate 3. Nanofiltration Heparin in Final Vial (Units/IU Factor IX) 0.04 >150 None >190 Specific Activity of Final Product (IU factor IX/mg total protein after addition of stabilizer) 25

9 TABLE III. PRODUCTS LICENSED IN THE U.S. TO TREAT VON WILLEBRAND DISEASE A. Desmopressin Formulations to Treat TYPE 1 and Some TYPE 2 VWD Product Name Manufacturer U.S. Distributor Formulation Recommended Dosage and Administration DDAVP Injection Ferring AB (Malmo, Sweden) Aventis Pharma For parenteral use (IV or SQ), 4 mcg/ml in a 10-ml vial mcg/kg, mixed in 30 ml normal saline solution, infused I.V. slowly over 30 minutes. May repeat after 24 hours mcg/kg by subcutaneous injection. May repeat after 24 hours. DO NOT USE IN CHILDREN UNDER THE AGE OF 2 YEARS. USE WITH CAUTION IN PREGNANT WOMEN DURING LABOR Stimate Nasal Spray for Bleeding Ferring AB (Malmo, Sweden) CSL Behring Nasal spray, l.5 mg/ml. The metered dose pump delivers 0.1 ml (150 mcg) per actuation. The bottle contains 2.5 ml with spray pump capable of delivering mcg doses or mcg doses. AND DELIVERY. In patients weighing 50 kg, give one spray in one nostril (dose = 150 mcg). In those weighing 50 kg, give one spray in each nostril (dose = 300 mcg). May repeat after 24 hours. DO NOT USE IN CHILDREN UNDER THE AGE OF 2 YEARS. USE WITH CAUTION IN PREGNANT WOMEN DURING LABOR AND DELIVERY. 26

10 TABLE III. PRODUCTS LICENSED IN THE U.S. TO TREAT VON WILLEBRAND DISEASE (Continued) B. Human Plasma-Derived Intermediate Purity Concentrates That Contain FACTOR VIII and VON WILLEBRAND FACTOR Product Name Manufacturer Method of Viral Alphanate Grifols 1. Affinity 2. Solvent/detergent (TNBP/polysorbate 80) 3. Dry heat (80 o C, 72h) Humate-P Wilate CSL Behring GmbH (Marberg, Germany) Octapharma (Vienna, Austria) 1. Pasteurization (60 o C, 10 hrs) 1. Solvent/detergent (TNBP/octoxynol-9) 2. Dry heat (100 o C, 2 hr) Heparin in Final Vial (units/ml) SpecificActivity of Final Product (IU VWF /mg total protein after addition of stabilizer) Ratio of VWF: FVIII FDA Approved for von Willebrand Disease? < :1 Yes None :1 Yes None >60 1:1 Yes 27

11 TABLE IV. PRODUCTS LICENSED IN THE U.S. TO TREAT PATIENTS WITH INHIBITORS A. Human Plasma-Derived Activated Prothrombin Complex Concentrate For Use In Patients With INHIBITORS TO FACTOR VIII or IX Product Name Manufacturer Method of Viral Depletion or FEIBA Baxter (Vienna, Austria) 1. Vapor heat (10h, 60 o C, 190 mbar plus 1h, 80 o C, 375 mbar) 2. Nanofiltration, 35nm Heparin in Final Vial (units/ml) None 0.8 Specific Activity of Final Product (IU factor/mg total protein after addition of stabilizer) 28

12 TABLE IV. PRODUCTS LICENSED IN THE U.S. TO TREAT PATIENTS WITH INHIBITORS (Continued) B. Recombinant FACTOR VIIa Concentrate For Use In Patients With INHIBITORS To FACTOR VIII or IX Product Name Manufacturer Generation Human or Animal Plasma- Derived Protein Used in Culture Medium NovoSeven RT Novo Nordisk (Bagsvaerd, Denmark) Second Newborn Calf Serum Method of Viral Depletion or 1. Affinity 2. Solvent/detergent (TNPB/polysorbate 80) Stabilizer In Final Vial 1. Mannitol, 25 mg/ml 2. Sucrose, 10 mg/ml Heparin in Final Vial (units/ml) None 29

13 TABLE V. PRODUCTS LICENSED IN THE U.S. TO TREAT RARE BLEEDING DISORDERS A. Human Plasma-derived Concentrate to Treat AFIBRINOGENEMIA and HYPOFIBRINOGENEMIA Product Name Manufacturer Method of Viral Stabilizer in Final Vial Heparin in Final Vial (units/unit factor IX) RiaSTAP CSL Behring 1. Pasteurization (60, 20 hours) Human albumin None 20 Specific Activity of Final Product (mg factor I/mg total protein after addition of stabilizer) 30

14 TABLE V. PRODUCTS LICENSED IN THE U.S TO TREAT RARE BLEEDING DISORDERS (Continued) B. Recombinant FACTOR VIIa Concentrate for Treatment of FACTOR VII Deficiency Product Name Manufacturer Generation Human or Animal Plasma-Derived Protein Used in Culture Medium NovoSeven RT Novo Nordisk (Bagsvaerd, Denmark) Method of Viral Depletion or Second Newborn Calf Serum 1. Affinity 2. Solvent/detergent (TNPB/polysorbate 80) Stabilizers In Final Vial 1. Mannitol, 25mg/ml 2. Sucrose, 10 mg/ml Heparin in Final Vial (units/ml) None 31

15 TABLE V. PRODUCTS LICENSED IN THE U.S. TO TREAT RARE BLEEDING DISORDERS (continued) C. Human Plasma-derived Concentrate to Treat FACTOR XIII Deficiency Product Name Manufacturer Method of Viral Corifact CSL Behring GmbH 1. Pasteurization (60, 10 hours) 2. Ion exchange Stabilizer in final vial 1. Human albumin 2. Glucose Heparin in Final Vial (units/unit factor IX) None Specific Activity of Final Product (units factor XIII/mg total protein after addition of stabilizer) 32

16 TABLE V. PRODUCTS LICENSED IN THE U.S. TO TREAT RARE BLEEDING DISORDERS (continued) D. Recombinant FACTOR XIII Concentrate for treatment of FACTOR XIII-A SUBUNIT deficiency Product Name Manufacturer Generation Human or Animal Plasma- Derived Protein Used in Culture Medium Method of Viral Depletion or TRETTEN NovoNordisk Third None 1. Affinity 2. Nanofiltration, 35 nm Stabilizer In Final Vial Heparin in Final Vial Specific Activity (IU factor XIII/mg total protein) Sucrose None

17 TABLE V. PRODUCTS LICENSED IN THE U.S TO TREAT RARE BLEEDING DISORDERS (Continued) E. Human Plasma-derived Prothrombin Complex Concentrates for Use In Patients With Deficiencies of FACTORS II and X. (NOTE THAT CONTENT OF THESE FACTORS VARIES FROM LOT TO LOT AND PRODUCT TO PRODUCT) Product Name Manufacturer Method of Viral Bebulin Baxter (Vienna, Austria) 1. Vapor heat (10h, 60 o C, 190 mbar pressure plus 1h, 80 o C, 375 mbar) 2. Nanofiltration, 35 nm Profilnine Grifols 1. Solvent/detergent (TNBP/ polysorbate 80) Heparin in Final Vial (units/unit factor IX) Specific Activity of Final Product (IU factor IX/mg total protein after addition of stabilizer) Relative Content of Factors (FIX = 100) < X> II> IX>VII None 4.5 II> IX= X>VII 34

18 TABLE VI. FACTOR PRODUCTS LICENSED IN THE U.S. FOR USE IN INDIVIUALS WITH THROMBOSIS RISK A. Products to Treat ANTITHROMBIN Deficiency Product Name Generic Manufacturer Method of Viral Depletion or ATryn Thrombate Antithrombin, recombinant human Antithrombin, plasmaderived GTC Biotherapeutics Grifols 1. Dry heat 2. Nanofiltration 3. Ion exchange chromatograp hy 1. Pasteurization (60, 10hrs) 2. Nanofiltration Stabilizer In Final Vial Heparin in Final Vial, IU/IU AT Human or Animal Plasma- Derived Protein Used in Culture Medium Specific Activity of Final Product (IU AT/mg total protein after addition of stabilizer) Glycine None Goat milk 7 IU AT activity/mg Alanine (0.075 to M) <0.1 IU N/A Minimum 6.4 IU AT activity/mg 35

19 TABLE VI. FACTOR PRODUCTS LICENSED IN THE U.S. FOR USE IN INDIVIUALS WITH THROMBOSIS RISK (continued) B. Products to Treat PROTEIN C Deficiency Product Name Generic Manufacturer Method of Viral Depletion or Ceprotin Protein C, plasmaderived Baxter 1. Detergent (Polysorbate 80) 2. Immuno-affinity 3. Vapor heating 10hr,60,190+25mb ar 1hr,80, mbar Stabilizer In Final Vial Albumin (8mg/mL) Heparin in Final Vial Trace amount Specific Activity of Final Product (IU PC/mg total protein after addition of stabilizer)

20 TABLE VII. BLOOD BANK COMPONENTS TO TREAT RARE BLEEDING DISORDERS A. Fresh Frozen Plasma Products To Treat Patients With FACTOR V and FACTOR XI Deficiency Product Name Manufacturer Distributor Method of Viral Depletion or Donor Retested Some Some community 1. Donors must test negative on Fresh Frozen community blood centers second donation in order for first Plasma blood centers donation to be released. Octaplas, frozen pooled plasma, ABO blood group specific Octapharma Octapharma 1. TNBP/Octoxynol-9 2. Immune neutralization 3. Affinity ligand for prion removal Pool Size, Number Volume per of Donors per Unit unit, ml ml ml 37

21 TABLE VII. BLOOD BANK COMPONENTSTO TREAT RARE BLEEDING DISORDERS (Continued) B. Cryoprecipitate To Treat Patients With DYSFIBRINOGENEMIA Product Name Manufacturer Distributor Method of Viral Depletion or Cryoprecipitate Some community Some community Cryoprecipitate, pooled blood centers Some community blood centers blood centers Some community blood centers Pool Size, Number of Donors per Dispensed Unit None None 5 6 Volume per unit, ml

22 TABLE VIII. ANTIFIBRINOLYTIC AGENTS A. Aminocaproic Acid Product GenericName BrandNam e Manufacturer Form Dosing Comments Aminocaproic Acid Amicar Xanodyne Clover (generic) Mikart (generic) Oral suspension, 250 mg/ml mg/kg po q 6 hr Aminocaproic Acid Amicar Xanodyne Tablet, mg/kg po q Clover (generic) 500 mg 6 hr Mikart (generic) 1 gm Aminocaproic Acid Amicar American Regent Hospira B. Tranexamic Acid IV, 250 mg/ml 1 gm/hr IV as continuous infusion Do not use in presence of hematuria Do not use in presence of hematuria Do not use in presence of hematuria Product Brand Name Manufacturer Form Dosing Comments Cyklokapron Pfizer IV, 100 mg/ml 10 mg/kg IV q 6-8 hr Do not use in presence of hematuria Lysteda Xanodyne PO, 650 mg tablets Adult dose: 1300 mg q 8 hr X 5 days during menses Pediatric dose: mg/kg q 8 hr X 5 days Patients should not take Prothrombin Concentrate Concentrates (PCCs) while on Lysteda 39