DEVELOPMENT AND SMALL-SCALE PRODUCTION OF A SEVERELY HEATED FACTOR-VIII CONCENTRATE

被引:15
作者
KNEVELMAN, A [1 ]
DEWIT, HJC [1 ]
POTSTRA, P [1 ]
VANDERDOES, JA [1 ]
机构
[1] RED CROSS BLOOD BANK,THE HAGUE,NETHERLANDS
关键词
D O I
10.1111/j.1423-0410.1994.tb00288.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The small-scale production of a severely heated factor VIII concentrate is described. As starting material for the production 48 units of fresh frozen plasma from whole-blood donations or 24 units of plasma from apheresis are used. During a glycine and sodium chloride fractionation, contaminating proteins are removed from a pooled extract of single-donor cryoprecipitates. The resulting factor VIII-rich precipitate is redissolved in freeze-drying buffer and this solution is desalted by diafiltration. After filtration, this solution is dispensed into 10 vials and frozen. The product is freeze dried, and heat treated at 80 degrees C for 72 h. The mean yield of the heat-treated product improved from 160 IU factor VIII per liter plasma at the start of the production to 215 IU per liter plasma after a modification of the purification process. The validation of the virus inactivation during freeze-drying and 80 degrees C heat treatment for 72 h showed a reduction of greater than or equal to 7.6 log PFU/ml for Sindbis and a reduction of greater than or equal to 6.4 log TCID50/ml for HIV-1. The factor VIII concentrate was clinically tested in 6 patients. It possessed a normal half-life, showed a high recovery and no side effects. A Dutch license was granted in June 1991 and since then this product has been routinely manufactured in three Dutch blood banks.
引用
收藏
页码:89 / 95
页数:7
相关论文
共 14 条
[1]   PREPARATION OF LYOPHILIZED HEAT-TREATED CRYOPRECIPITATES FROM A SMALL POOL OF PLASMA OBTAINED BY APHERESIS [J].
ALLERSMA, DP ;
ROEFFEN, E ;
VANDERDOES, JA ;
BRIET, E .
PHARMACEUTISCH WEEKBLAD-SCIENTIFIC EDITION, 1991, 13 (01) :18-23
[2]   QUALITY-CONTROL PROGRAM FOR THE PREPARATION OF SMALL-POOL LYOPHILIZED HEAT-TREATED CRYOPRECIPITATES [J].
ALLERSMA, DP ;
SWUSTE, F ;
BRIET, E ;
VANDERDOES, JA .
PHARMACEUTISCH WEEKBLAD-SCIENTIFIC EDITION, 1991, 13 (01) :24-31
[3]   MODIFIED GLYCINE PRECIPITATION TECHNIQUE FOR THE PREPARATION OF FACTOR-VIII CONCENTRATE OF HIGH-PURITY AND HIGH-STABILITY [J].
BRODNIEWICZPROBA, T ;
BEAUREGARD, D .
VOX SANGUINIS, 1987, 52 (1-2) :10-14
[4]  
COLOMBO M, 1985, LANCET, V2, P1
[5]  
Dodge H. F., 1977, Journal of Quality Technology, V9, P120
[6]  
LAHAYE JWT, 1990, NED T ANESTHESIOL, V3, P184
[7]  
MASON EC, 1978, LANCET, V2, P15
[8]   MULTI-VARIATE ANALYSIS OF FACTORS GOVERNING THE PHARMACOKINETICS OF EXOGENOUS FACTOR-VIII IN HEMOPHILIACS [J].
MESSORI, A ;
LONGO, G ;
MORFINI, M ;
CINOTTI, S ;
FILIMBERTI, E ;
GIUSTARINI, G ;
FERRINI, PR .
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY, 1988, 35 (06) :663-668
[9]  
PASI KJ, 1990, LANCET, V335, P1473, DOI 10.1016/0140-6736(90)91511-8
[10]   PRODUCTION OF HIGH-POTENCY CONCENTRATES OF ANTIHEMOPHILIC GLOBULIN IN A CLOSED-BAG SYSTEM - ASSAY IN VITRO AND IN VIVO [J].
POOL, JG ;
SHANNON, AE .
NEW ENGLAND JOURNAL OF MEDICINE, 1965, 273 (27) :1443-&