PMID- 9352057
OWN - NLM
STAT- MEDLINE
DCOM- 19980202
LR  - 20191102
IS  - 1073-1199 (Print)
IS  - 1073-1199 (Linking)
VI  - 25
IP  - 6
DP  - 1997 Nov
TI  - Validation of the heat treatment step used in the production of diaspirin 
      crosslinked hemoglobin (DCLHb) for viral inactivation--effect of crosslinking.
PG  - 521-6
AB  - Two experiments were performed to assess viral inactivation during the 
      crosslinking and heat treatment steps of the DCLHb manufacturing process. Stroma 
      free hemoglobin (SFHb) collected from a large scale manufacturing lot was tested 
      in a 1:680 scaled down system in which the key parameters used in the 
      manufacturing process were replicated. In the first study Porcine Parvovirus 
      (PPV), a non-enveloped virus, was used to assess inactivation, while in the 
      second study Bovine Viral Diarrhea Virus (BVDV), an enveloped virus, was 
      utilized. In both experiments, the SFHb solution was deoxygenated and an aliquot 
      of virus suspension was added. To initiate the crosslinking reaction, a solution 
      of bis (3,5-dibromosalicyl) fumarate (DBBF) in HEPES buffer was added to the test 
      solution. In both experiments the reaction times and the degree of crosslinking 
      were normal. After crosslinking, the reaction mixtures were heated to 74 +/- 1 
      degrees C over 30 minutes, held at 74 +/- 1 degrees C for 90 minutes, and cooled 
      to less than 10 degrees C over 30 minutes. In each experiment the degree of 
      crosslinking of final product was 100% and yield of hemoglobin recovery was 
      normal. Samples were removed prior to crosslinking, after crosslinking and 
      before, during and after heat treatment for determination of virus titer and 
      evaluation of key process parameters. The results from these experiments were 
      consistent with those obtained from the full scale manufacturing process for the 
      deoxygenation, crosslinking and the heat treatment step during the production of 
      DCLHb. The results of virus assays showed that crosslinking has no effect on 
      viruses and their subsequent inactivation by heat treatment.
FAU - Azari, M
AU  - Azari M
AD  - Blood Substitutes Program, Baxter Healthcare Corporation, Round Lake, Illinois 
      60073, USA.
FAU - Catarello, J
AU  - Catarello J
FAU - Burhop, K
AU  - Burhop K
FAU - Camacho, T
AU  - Camacho T
FAU - Ebeling, A
AU  - Ebeling A
FAU - Estep, T
AU  - Estep T
FAU - Guzder, S
AU  - Guzder S
FAU - Krause, K
AU  - Krause K
FAU - Marshall, T
AU  - Marshall T
FAU - Rohn, K
AU  - Rohn K
FAU - Sarajari, R
AU  - Sarajari R
FAU - Boose, J A
AU  - Boose JA
FAU - Gauvin, G
AU  - Gauvin G
FAU - Horner, R
AU  - Horner R
FAU - Lu, B
AU  - Lu B
FAU - Pearson, L
AU  - Pearson L
FAU - Vacante, D
AU  - Vacante D
LA  - eng
PT  - Journal Article
PL  - England
TA  - Artif Cells Blood Substit Immobil Biotechnol
JT  - Artificial cells, blood substitutes, and immobilization biotechnology
JID - 9431307
RN  - 0 (Cross-Linking Reagents)
RN  - 0 (Hemoglobins)
RN  - FXP28WJO7L (diaspirin-cross-linked hemoglobin)
RN  - R16CO5Y76E (Aspirin)
SB  - IM
MH  - Animals
MH  - Aspirin/*analogs & derivatives/metabolism
MH  - Cattle
MH  - Cross-Linking Reagents/*metabolism
MH  - Diarrhea Viruses, Bovine Viral/*growth & development
MH  - Hemoglobins/*metabolism
MH  - *Hot Temperature
MH  - Parvovirus/*growth & development
MH  - Swine
MH  - *Viral Plaque Assay
EDAT- 1997/11/14 00:00
MHDA- 1997/11/14 00:01
CRDT- 1997/11/14 00:00
PHST- 1997/11/14 00:00 [pubmed]
PHST- 1997/11/14 00:01 [medline]
PHST- 1997/11/14 00:00 [entrez]
AID - 10.3109/10731199709117449 [doi]
PST - ppublish
SO  - Artif Cells Blood Substit Immobil Biotechnol. 1997 Nov;25(6):521-6. doi: 
      10.3109/10731199709117449.