Precipitation of Process-Derived Impurities in Non-Protein A Purification Schemes for Antibodies - Precipitation prior to capture chromatography offers a simple, robust, and economical method to

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Precipitation of Process-Derived Impurities in Non-Protein A Purification Schemes for Antibodies
Precipitation prior to capture chromatography offers a simple, robust, and economical method to remove CHO host cell proteins and DNA.


BioPharm International Supplements


Conclusions

The potential application of already successful and proven alternative technologies from other areas has been explored for antibody purification.11 High throughput process steps that are desirable for handling escalating titers will find their place in future large-scale manufacturing processes. Precipitation is one such alternative, and when applied to either the product or contaminants12 it significantly reduces demand on downstream steps. In addition, the precipitation of contaminants directly in the cell culture offers the further advantage of reducing unit operations at large-volume stages of the recovery processes. Because the precipitation step for cell culture can be performed directly in the bioreactor, using a disposable bioreactor is very convenient and lessens the burden of cleaning validation. Clearly, for a generic two-step non-affinity process, we have demonstrated a significant reduction in the cost of goods as well as improvements in productivity for a model HuMAb manufacturing process.12 However, economic comparisons need to be extended to various processes to account for different purification schemes and manufacturing scales used for each molecule.

JUE (MICHELLE) WANG, PhD, is the assistant director of purification process development, TIMOTHY DIEHL and DEENA AGUIAR are scientists in purification process development, XIAO-PING DAI, PhD, is the assistant director of bioprocess development, and ALAHARI ARUNAKUMARI is the senior director of process development,.all at Medarex, Inc., 908.479.2451,

References

1. Wang J, Diehl T, Watkins-Fischl M, Perkins D, Aguiar D, and Arunakumari A. Optimizing the primary recovery step in non-affinity purification schemes for HuMabs. BioPharm International, 2008, March supplement: 4-10.

2. Sundar, R. and R. Stenson. (2008). Method of Isolating Antibodies by Precipitation. WO 2008/100578 A2.

3. Habeeb A, Francis R. Preparation of human immunoglobulin by ammonium sulfate precipitation. Vox Sang. 1976;31:423-434.

4. Thommes, Gottschalk U. Alternatives to packed-bed chromatography for antibody extraction and purification. A book Chapter in Process Scale Purification of Antibodies. Edited by U. Gottschalk. Published by John Wiley & Son, Inc. (2009)

5. Clark K, Glatz C. Polymer dosage considerations in polyelectrolyte precipitation of protein. Biotechnol Prog. 1987;3(4):241-247.

6. Glynn J. Process-scale precipitation of impurities in mammalian cell culture broth. BioPharm International, 2008, March supplment: 12-18.

7. Glynn J. Process-scale precipitation of impurities in mammalian cell culture broth. A book Chapter in Process Scale Purification of Antibodies. ;Edited by U. Gottschalk. Published by John Wiley & Son, Inc. (2009)

8. Russell E, Wang A, Rathore A.S. Harvest of a therapeutic protein product from high cell density fermentation broths: principles and case study. A book chapter in Process scale bioseparations for the biopharmaceutical industry edited by Shukla A., Etzel M, Gadam S. published by CRC Press, Taylor & Francis group (2007).

9. Faber R. Novel membrane adsorbers for large scale downstream processing. 6th HIC/RPC Bioseparation conference, Napa, March 15-19, 2009.

10. Seng R.L., Lundblad J.L. Viral inactivation process. US patent number 4939176, July 3, 1990.

11. Gottschalk, U. The renaissance of protein purification. BioPharm International, 2006, June Supplement: 8-9.

12. Arunakumari, A., Wang J. and G. Ferreira. Advances in non-protein A purification processes for Human Monoclonal Antibodies. Biopharm International, 2009, March supplement: 22-26.


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