Manufacture and in vitro Characterization of a Solvent/Detergent-Treated Human Plasma

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Abstract
We have developed a modified solvent/detergent (S/D) treatment to inactivate viruses in human plasma using 1% w/w final concentrations of tri(n-butyl) phosphate (TNBP) and Triton X-100 and an incubation period of 4 h at 30°C. The procedure inactivates ≥10^6 chimpanzee-infectious doses (CID(50)) of HBV, ≥10^5 CID(50) of HCV. and ≥10^6 tissue culture infectious doses (TCID(50)) of HIV. After virus inactivation, eleven plasma batches were lyophilized and 12 batches were deep-frozen until further use. The batches were characterized by extensive laboratory tests including measurement of clotting factors I—XIII. von Willebrand factor, plasminogen, inhibitors of blood coagulation and fibrinolysis, and other clinically important plasma proteins. All parameters were determined before and after S/D treatment. Twelve conventional single donor plasma units served as control. There were no marked losses of activities of clotting factors, antithrombin III, protein C. plasminogen, and Cl-esterase inhibitor due to treatment. After the S/D step, the levels of these parameters were within the normal range in all batches. The same holds true for total protein, immunoglobulins, albumin, complement factors C3 and C4, haptoglobin, hemopexin, caeruloplasmin, α(1)-antitrypsin, and pH. Protein S and α(2)-antiplasmin activites decreased by about 50% and were frequently found to be slightly below the lower limit of the respective normal range after treatment. The interindividual variations of all proteins analysed were significantly lower than in the single donor plasma units. The S/D procedure did not lead to increases of markers indicating activation of hemostasis. We conclude that lipid-enveloped viruses can be inactivated by the S/D procedure described in this study without critical reduction of recoveries of plasma proteins.

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