COG WITH DISPOSABLE MEMBRANE CHROMATOGRAPHY
Figure 4. CoG results for a typical 2,000 L scale production process based on stainless steel equipment using reusable resin
and when resin is replaced by disposable membrane chromatography.
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When the process is based on stainless steel equipment including reusable resin chromatography column, the overall CoG is
$192/g of MAb. The CoG decreases to $184/g when reusable resin is replaced by disposable membrane chromatography (Figure 4).
The need for capital requirement is reduced in the membrane chromatography option with 3% capital savings. Disposable membrane
chromatography simplifies hardware installation, adding flexibility to the process. Despite a 0.3% increase in consumable
cost, the overall CoG savings with disposable membrane chromatography is 4% because of reduced capital requirements, labor,
and buffer and water consumption. The disposable chromatography option has the advantage of switching some of the capital
costs to consumables costs that are only relevant when the plant is operational.
Figure 5. Water usage for a 2,000 L scale production process based on stainless equipment using reusable resin and when resin
is replaced with disposable membrane chromatography.
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Figure 5 represents the water and cleaning material usage with the Q membrane and Q resin. As we looked at the whole process,
the buffer savings from the membrane is minimized because of the elimination of the CIP and SIP requirements that must be
performed on the stainless steel-based equipment. A 3% water usage savings is observed with the membrane technology.
ENVIRONMENTAL EFFECT OF DISPOSABLE TECHNOLOGIES
The increasing interest in disposable technology naturally has been followed by a growing concern about the environmental
impact because of the solid plastic waste being generated from their use. Sinclair, et al., have compared the environmental
footprint of a traditional biopharmaceutical manufacturing facility using fixed-in-place stainless steel equipment and a facility
implementing disposable technologies.17 This paper demonstrated that the overall waste streams were reduced with disposable technologies, specifically water load
and people requirements. A 25.5% reduction in CO2 emissions was estimated for the facility using disposables relative to the traditional stainless steel-equipped facility.
The reduction in CO2 emission mainly is derived from the reduced usage of water, which more than compensates for the emission of CO2 associated with the use of plastics (i.e., between polymerization, transportation, and incineration).
CONCLUSIONS
Disposable membrane chromatography significantly reduces the need for water load. Water and buffer usage is 95% less for disposable
membrane chromatography because there are no CIP or SIP procedures. Because of its hydrodynamic benefits, membrane adsorbers
can operate at much higher flow rate or lower residence time than columns, thereby shortening the overall process time and
reducing labor requirements and energy consumption. The smaller membrane device sufficient to process the required throughput
reduced the plant footprint and operating costs.
The availability of membrane chromatography as prepacked, disposable, and portable capsules eliminates the need for packing
and packing testing, cleaning, and cleaning validation, and adds safety to the product by preventing cross-contamination.
Interest in membrane chromatography has grown because it can be used as a disposable device while maintaining product with
the required purity; and it has been much discussed in the literature that single-use system has lower an environmental impact.17,18
Nathalie Fraud, PhD, is senior scientist, purification technologies, at Sartorius Stedim North America, Bohemia, NY, 626.241.2171 nathalie.fraud@sartorius-stedim.com
Janice Lim, PhD, is bioprocess consultant and Andrew Sinclair is the managing director, both at Biopharm Services Ltd, Chesham Buckinghamshire, UK. Uwe Gottschalk, PhD, is vice president of purification technologies at Sartorius Stedim Biotech GmbH, Göttingen, Germany. Gottschalk is also
a member of BioPharm International's editorial advisory board.
REFERENCES
1. Gottschalk U. Bioseparation in antibody manufacturing: the good, the bad, and the ugly. Biotechnol Prog. 2008;24:496–503.
2. Davis J. A purification platform for the production of mAbs from fermenters with titers of 5 g/L and beyond. BioPharm
Int. 2009 Oct Supplement:20–3.
3. Davis J. Economics of Monoclonal Antibody Production; the relationship between upstream title and downstream costs. IBC
San Diego 2008.
4. Low D, O'Leary R, Pujar NS. Future of antibody purification. J Chromatogr B. 2007;848:48–63.
5. Schukla A, Hubbard B, Tressel T, Guhan S, Low D. Downstream processing of monoclonal antibodies—application of platform
approaches. J Chromatogr B. 2007;848:28–39.
6. Thoemmes J, Etzel M. Alternatives to chromatographic separations. Biotechnol Prog. 2007;23:42–5.
7. Przybycien TM, Pujar NS, Steele LM. Alternative bioseparation operations: life beyond packed-bed chromatography. Curr
Opin Biotechnol. 2004;15:469–78.
8. Fraud N. Membrane chromatography: an alternative to polishing column chromatography. Bioproc J. 2008;7:34–7.
9. Arunakumari A, Wang J, Ferreira G. Advances in non-Protein A purification processes for human monoclonal antibodies. BioPharm
Int. 2009 Mar Supplement:22–6.
10. Gottschalk U, Fischer-Fruehholz S, Reif O. Membrane adsorbers, a cutting edge process technology at the threshold. BioProc
Int. 2004;2:56–65.
11. DiBasi K, Jornitz M, Gottschalk U, Priebe PM. Disposable biopharmaceutical processes—myth or reality? BioPharm Int. Nov
2006.
12. Lim JA, C, Sinclair A, Kim DS, Gottschalk U. economic benefits of single-use membrane chromatography in polishing—a cost
of goods model. BioProc Int. Feb 2007;48–56.
13. Zhou JX, Tressel T. Basic concepts in Q membrane chromatography for large-scale antibody production. Biotechnol Prog.
2006;22:341–9.
14. Zhou JX, Tressel T, Gottschalk U, Solamo F, Pastor A, Dermawan S, Hong T, Reif O, Mora J, Hutchison F, Murphy M. New
Q membrane scale-down model for process-scale antibody purification. J Chromatogr A. 2006;1134:66–73.
15. Zhou J, Tressel T, Guhan S. Disposable chromatography. Single-use membrane chromatography as a polishing option during
antibody production is gaining momentum. Biopharm Int. 2007, Supplement Feb. 26–35.
16. Lim JAC, Sinclair A. Process economy of disposable manufacturing—process models to minimize upfront investment. Amer
Pharmaceut Rev. 2007;10:114–21.
17. Sinclair A, Leveen L, Monge M, Lim J, Cox S. The Environmental Impact of Disposable Technologies. Can disposable technology
reduce your facility's environmental footprint? BioPharm Int. 2008 Nov Supplement:4–15.
18. Leveen L. Single-use technology and the carbon and water footprints of biopharm manuf. Amer Pharmaceut Rev. 2009 Sept/Oct;72–8.
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