Bracketed generic inactivation of rodent retroviruses by low pH treatment for monoclonal antibodies and recombinant proteins
- 21 February 2003
- journal article
- research article
- Published by Wiley in Biotechnology & Bioengineering
- Vol. 82 (3), 321-329
- https://doi.org/10.1002/bit.10574
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 log10 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 log10 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 pI, 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 log10 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.Keywords
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