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Bracketed generic inactivation of rodent retroviruses by low pH treatment for monoclonal antibodies and recombinant proteins
Author(s) -
Brorson Kurt,
Krejci Sherrie,
Lee Kitty,
Hamilton Elizabeth,
Stein Kathryn,
Xu Yuan
Publication year - 2003
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.10574
Subject(s) - recombinant dna , monoclonal antibody , retrovirus , chemistry , murine leukemia virus , antibody , endogeny , in vitro , virus inactivation , chromatography , biochemistry , virology , virus , biology , immunology , gene
Abstract Viral safety is a predominant concern for monoclonal antibodies (mAbs) and other recombinant proteins (RPs) with pharmaceutical applications. Certain commercial purification modules, such as nanofiltration and low‐pH inactivation, have been observed to reliably clear greater than 4 log 10 of large enveloped viruses, including endogenous retrovirus. The concept of “bracketed generic clearance” has been proposed for these steps if it could be prospectively demonstrated that viral log 10 reduction value (LRV) is not impacted by operating parameters that can vary, within a reasonable range, between commercial processes. In the case of low‐pH inactivation, a common step in mAb purification processes employed after protein A affinity chromatography, these parameters would include pH, time and temperature of incubation, the content of salts, protein concentration, aggregates, impurities, model protein p I , and buffer composition. In this report, we define bracketed generic clearance conditions, using a prospectively defined bracket/matrix approach, where low‐pH inactivation consistently achieves ≥4.6 log 10 clearance of xenotropic murine leukemia virus (X‐MLV), a model for rodent endogenous retrovirus. The mechanism of retrovirus inactivation by low‐pH treatment was also investigated. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 82: 321–329, 2003.