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Polyacrylic acid based plasma fractionation for the production of albumin and IgG: Compatibility with existing commercial downstream processes
Author(s) -
McCann Karl B.,
Van Alstine James,
Martinez Jose,
Shanagar Jamil,
Bertolini Joseph
Publication year - 2020
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.27265
Subject(s) - chromatography , chemistry , downstream processing , fractionation , precipitation , ethanol precipitation , polyacrylic acid , extraction (chemistry) , polymer , organic chemistry , physics , meteorology
Commercial fractionation of human plasma into immunoglobulin‐ and albumin‐rich fractions is often initiated with sequential cold ethanol‐based precipitation methods, which have changed little over the past 70 years. The required low temperature (−4 to −8°C) and high concentrations of ethanol 8–40%) necessitate large‐scale fixed processing lines, and major capital investment and operating costs. The resulting fractions are then further purified by ethanol based precipitation or chromatographic procedures to obtain the purified final product. Aqueous polyacrylic acid (PAA) based precipitation, which readily interfaces with existing downstream processing, could offer advantages with respect to cost, safety, environmental impact, and flexibility. Sequential precipitation with 7%, 12%, and 20% (w/v) solutions of PAA 8000 in the presence of a kosmotropic salt (sodium citrate) gave fibrinogen‐, immunoglobulin‐, and albumin‐rich fractions with 80–90% yield and 64%, 55%, and 82% purity, respectively. Further purification of the IgG‐rich precipitate by caprylic acid precipitation and anion exchange chromatography, achieved a target purity of >99%. This was also achieved for the downstream processing of the albumin‐rich precipitate using a two‐step ion exchange chromatographic procedure. This work shows that PAA precipitation can be used in place of cold ethanol precipitation to generate crude IgG and albumin fractions which can be purified to final products of acceptable purity.