title: Evaluation and validation of virus removal by ultrafiltration during the production of diaspirin crosslinked haemoglobin (DCLHb).
abstract: Virus retention during ultrafiltration through A/G Technology filter cartridges was investigated to characterize the removal process and validate the degree of virus titre reduction during the filtration of red blood cell haemolysates performed as part of the production of diaspirin crosslinked haemoglobin (DCLHb). When viruses were suspended in phosphate buffered saline solution, retention was greater with larger sized viruses and smaller filter pore size. Virus titre was maintained at starting levels in the filter retentate circuit during the course of filtration, suggesting that the virus removal mechanism is predominantly size exclusion. Evaluation of specific processing variables indicated that the retention of phiX174 virus was increased in the presence of red blood cell haemolysate or at high membrane crossflow rates and transmembrane pressures, while the retention of EMC virus was less sensitive to variations in these parameters. Using these results to design a validation protocol, log reduction values of >7.9 were demonstrated for the retention of human immunodeficiency virus, pseudorabies virus and bovine viral diarrhoea viruses, 7.6 for hepatitis A virus, and 4.2 for porcine parvovirus. It was also shown that the retention of viruses was maintained during repetitive use of the same filter cartridge.
authors.affiliation: Hemoglobin Therapeutics Program, Baxter Healthcare Corporation, Round Lake, IL 60073-9799, USA.
authors.forename: M
authors.initials: M
authors.lastname: Azari
authors.forename: J A
authors.initials: JA
authors.lastname: Boose
authors.forename: K E
authors.initials: KE
authors.lastname: Burhop
authors.forename: T
authors.initials: T
authors.lastname: Camacho
authors.forename: J
authors.initials: J
authors.lastname: Catarello
authors.forename: A
authors.initials: A
authors.lastname: Darling
authors.forename: A A
authors.initials: AA
authors.lastname: Ebeling
authors.forename: T N
authors.initials: TN
authors.lastname: Estep
authors.forename: L
authors.initials: L
authors.lastname: Pearson
authors.forename: S
authors.initials: S
authors.lastname: Guzder
authors.forename: J
authors.initials: J
authors.lastname: Herren
authors.forename: K
authors.initials: K
authors.lastname: Ogle
authors.forename: J
authors.initials: J
authors.lastname: Paine
authors.forename: K
authors.initials: K
authors.lastname: Rohn
authors.forename: R
authors.initials: R
authors.lastname: Sarajari
authors.forename: C S
authors.initials: CS
authors.lastname: Sun
authors.forename: L
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000302:isolation & purification; D010584:Bacteriophage phi X 174; D002460:Cell Line; D001908:Diarrhea Viruses, Bovine Viral; D004340:Drug Contamination; D004686:Encephalomyocarditis virus; D004867:Equipment Design; D004912:Erythrocytes; D005069:Evaluation Studies as Topic; D006678:HIV; D006454:Hemoglobins / Q000302:isolation & purification*; D006461:Hemolysis; D006507:Hepatovirus; D011558:Herpesvirus 1, Suid; D006801:Humans; D008253:Macaca mulatta; D008567:Membranes, Artificial; D010316:Particle Size; D017992:Parvovirus; D012449:Safety; D013552:Swine; D014462:Ultrafiltration / Q000295:instrumentation; D010948:Viral Plaque Assay; D014780:Viruses
chemical_list: D006454:Hemoglobins; D008567:Membranes, Artificial; C083478:diaspirin-cross-linked hemoglobin; D001241:Aspirin