Upcoming Technologies to Facilitate More Efficient Biologics Manufacturing - Choosing the right tools to enhance the process. - BioPharm International


Upcoming Technologies to Facilitate More Efficient Biologics Manufacturing
Choosing the right tools to enhance the process.

BioPharm International
Volume 22, Issue 2


Figure 8
As discussed above, single-use technologies offer higher productivity in terms of process time (cleaning is not required) as well as floor space (no cleaning equipment). However, to maximize the benefit, the technology should provide the whole unit operation. For example, in the case of chromatography step, using a single-use column alone yields only partial benefit as the chromatography skid still requires cleaning post-use. The ReadyToProcess program at GE Healthcare Bio-Sciences AB (Uppsala, Sweden) aims to provide a more integrated solution that includes the prepacked, presanitized, and prequalified columns and a chromatography system with a disposable flow path. The flow path is also presanitized and contains an air-trap, UV and conductivity meters, and a flow meter. The flow path can be assembled on the system in less than 10 minutes. As seen in Figure 8, implementation of this technology could lead to reduction in changeover time by up to three days, from seven to four days. This reduction would give a 20% to 30% increase in the number of batches produced per year for a 49-week production schedule based on seven or 14-day production campaigns, respectively. Furthermore, if changeover time is reduced to no more than one day per production line, without disrupting any of the operation ongoing in the production suite (the parallel production line concept), then the increase in the number of extra batches made per year could be between 40 to 160%. The exact efficiency depends on the changeover time and the length of a single campaign. While a similar increase in number of batches could be achieved by using duplicate columns and skids such that the cleaning is performed when the column and skid are offline, this will require a significantly higher capital expenditure and floor space for the duplicate columns and skids. Another possibility is to use a single system for all chromatography steps during manufacturing of a single batch. This will result in reduction of the cost of equipment by 66% as well as lower floor space requirement.

Figure 9
Figure 9 presents a comparison of break-even plot for conventional and ReadyToProcess based operations. The analysis assumes that: 1) each batch produced generates the same level of revenues, either current or future; 2) the fixed cost for the conventional operation is three times higher than for the ReadyToProcess one; and, 3) the operating cost per batch for the conventional technology is 50% lower. The two arrows in the figure show the level of net income after tax for the reference (conventional) case and the case when 40% more batches can be produced per year, respectively. The increase in the number of batches is related to the decrease in changeover time. It is seen that the higher operating cost associated with the use of single-use technologies is outweighed by significantly lower capital cost contribution. Thus, an introduction of such technologies results in a higher net income as long as number of batches produced using these ready-to-use technologies is larger than the number of batches that could be produced using conventional techniques. A real revenue curve for an average biologic is expected to be steeper than the revenue curve shown in Figure 9.

Technologies enabling quick changeover times, and at the same time providing high manufacturing flexibility allowing quick responses to market demands, will become more popular because they offer higher productivity as well as better economics.

Xuemin Liu is marketing manager and Mike Collins is senior R&D engineer, applications, both at Pall Life Sciences, East Hills, NY; Nathalie Fraud is senior scientist, purification process development at Sartorius Stedim North America, Edgewood, NY; Jennifer Campbell is field marketing manager and Inese Lowenstein is director, virus safety solutions, both at Millipore Corporation, Billerica, MA; Karol M. Lacki is R&D staff scientist at GE Healthcare Bio-Sciences AB, Uppsala, Sweden; and Anurag S. Rathore is the director of process development at Amgen, Inc.,

Thousand Oaks, CA, 805.447.4491,
. Rathore is also a member of BioPharm International's editorial advisory board.


1. Rathore AS, Winkle H. Quality by Design for pharmaceuticals: I. Regulatory perspective and approach. Nature Biotechnol. 2009;27:26–34.

2. Kozlowski S, Swann P. Current and future issues in the manufacturing and development of monoclonal antibodies. Advanced Drug Delivery Rev. 2006;58:707–722.

3. Yu L. Pharmaceutical quality by design: product and process development, understanding and control. Pharm Research. 2008;25:781–791.

4. Rathore AS, Saleki-Gerhardt A, Montgomery SH, Tyler SM. Quality by Design for pharmaceuticals: industrial case studies on defining and implementing design space for the process. BioPharm Int. Part 1: 2008;21(12):37–41 and Part 2: 2009;22(1)–44.

5. Shukla AA, Rao JR Harvest and recovery of monoclonal antibodies from large-scale mammalian cell culture. BioPharm Int. 2008;21:34–45.

6. Roush DJ, Lu Y. Advances in primary recovery: centrifugation and membrane technology. Biotechnol Progress. 2008;24:488–495.

7. Wang A, Lewus R, Rathore AS. Comparison of different options for harvest of a therapeutic protein product for high cell density fermentation broth. Biotech Bioengg. 2005:94;91–104.

8. Fraud N. Membrane chromatography: an alternative to polishing column chromatography. BioProcessing J. 2008;7:34–38.

9. Zeng X, Ruckenstein E. Membrane chromatography: preparation and applications to protein separation. Biotechnol Prog. 1999;15:1003–1019.

10. International Conference on Harmonization. Harmonized Tripartate Guideline: Q5A Viral Safety of Biotechnology Products Derived from Cell Lines of Human or Animal Origin. Fed. Reg. 63 (185) 24. 1998 Sep: 51074. Available from http://www.ich.org/LOB/media/MEDIA425.pdf.

11. US Food and Drug Administration. Points to consider in the manufacture and testing of monoclonal antibody products for human use. CBER. Rockville, MD; 1997. Available from: http://www.fda.gov/cber/gdlns/ptc_mab.pdf.

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