Process for obtaining high efficiency human albumin for use in detoxification therapy
A process for purifying and collecting albumin from plasma and plasma fractions involves diafiltration of an albumin-containing plasma fraction; stabilizing the resulting albumin fraction with sodium chloride and an amino acid in the absence of any added fatty acid; pasteurizing the stabilized albumin fraction; and diafiltering the pasteurized fraction to remove, along other things, stabilizers. In one embodiment, the amino acid stabilizing agent is acetyl tryptophan. The resulting albumin has at least about 80% albumin binding capacity relative to natural plasma albumin, and is storage stable for about 30 months at 30° C.
1. A process for obtaining albumin from plasma comprising:
a) diafiltration of an albumin-containing plasma fraction;
b) stabilizing the diafiltered albumin fraction with NaCl and one or more amino acids and in the absence of any added fatty acids;
c) pasteurizing the stabilized albumin fraction; and
d) diafiltration of the pasteurized albumin fraction,
wherein the resulting albumin has albumin binding capacity of at least about 80% relative to natural human plasma albumin.
2. The process of claim 1 , wherein the plasma fraction is human plasma.
3. The process of claim 1 , wherein the pasteurizing of step (c) is effected at a temperature and duration sufficient to inactivate viruses and reduce PKA content.
4. The process of claim 3 , wherein the pasteurizing is performed by heating the stabilized albumin fraction to 61±2° C.
5. The process of claim 4 , wherein the stabilized albumin fraction is heated for 10.5±0.5 hours.
6. The process of claim 1 , wherein the albumin is stabilized by adjusting the fraction to at least 0.15 M NaCl.
7. The process of claim 6 , wherein the amino acid is N-acetyltryptophan.
8. The process of claim 7 , wherein the albumin is stabilized by adjusting the fraction to at least 0.096 mmol of N-acetyltryptophan/gram albumin.
9. The process of claim 1 , wherein the diafiltration of step (d) is carried out such that it removes substances binding to albumin that reduce the its binding capacity of albumin.
10. The process of claim 1 , wherein the diafiltration of step (d) is carried out to achieve an albumin fraction that is about 0.15 M NaCl and a protein concentration of about 3.5 to 25%.
11. The process of claim 1 , further comprising sterilization of the stabilized albumin fraction by passing it through a filter of pore size 0.2 μm.
12. The process of claim 1 , wherein diafiltration is performed using a membrane having a nominal molecular cutoff of 1-50 kDa.
13. The process of claim 1 , wherein the resulting albumin retains at least about 80% albumin binding capacity on storage for 30 months at 30° C.±2° C.
14. The process of claim 1 , wherein the diafiltration of step (d) removes added amino acid of step (b).
15. The process of claim 1 , wherein a diafiltration step is performed on a NaCl solution.
16. The process of claim 15 , wherein a diafiltration step is performed on no less than 3 volumes of NaCl solution.
17. The process of claim 15 , wherein a diafiltration step is performed on no less than 7 volumes of NaCl solution.
18. The process of claim 15 , wherein a diafiltration step on a NaCl solution is followed by diafiltration on water.