Parvovirus B19 DNA in Factor VIII concentrates: effects of manufacturing procedures and B19 screening by nucleic acid testing.
BACKGROUND
Parvovirus B19 (B19) is a common contaminant, especially in coagulation factors. Because of B19 transmission by pooled plasma, solvent/detergent treated in 1999, some fractionators initiated minipool nucleic acid testing (NAT) to limit the B19 load in manufacturing pools. In this study, the extent of B19 DNA contamination in commercial Factor VIII concentrates, that is, antihemophilic factor (human) (AHF), manufactured before and after B19 NAT screening was implemented, was determined.


METHODS
A total of 284 lots representing six AHF products made during 1993 to 1998 and 2001 to 2004 were assayed for B19 DNA by an in-house NAT procedure. Anti-B19 immunoglobulin G (IgG) was also measured.


RESULTS
Most lots made during 1993 to 1998 had detectable B19 DNA. The prevalence ranged from 56 to 100 percent and appeared to differ between manufacturers. The highest level of B19 DNA found was 10(6) genome equivalents (geq or international units [IU]) per mL. Forty percent of the lots tested contained 10(3) geq (IU) per mL. In comparison, both prevalence and levels in source plasma-derived AHF products made in 2001 to 2004 were lower. Both, however, remained unchanged in the recovered plasma-derived product because B19 NAT screening had not been implemented. Only an intermediate-purity AHF product was positive for the presence of anti-B19 IgG.


CONCLUSIONS
The prevalence and levels of B19 DNA in AHF prepared from B19 NAT unscreened plasma were high but varied among products with different manufacturing procedures. B19 NAT screening of plasma effectively lowered the B19 DNA level in the final products and in the majority of cases rendered it undetectable and hence potentially reduced the risk of B19 transmission.
Geng
Yansheng
Y
Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA.
Wu
Chuan-Ging
CG
Bhattacharyya
Siba P
SP
Tan
De
D
Guo
Zheng-Ping
ZP
Yu
Mei-ying W
MY
D000956:Antigens, Viral / Q000097:blood; D004279:DNA, Viral / Q000097:blood*; D004340:Drug Contamination / Q000517:prevention & control; D005169:Factor VIII / Q000032:analysis*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016732:Parvovirus B19, Human / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D010949:Plasma / Q000737:chemistry / Q000821:virology
D000956:Antigens, Viral; D004279:DNA, Viral; D007074:Immunoglobulin G; D005169:Factor VIII