The Use of Disposable and Alternative Purification Technologies for ...

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Impact of increasing cell culture titer and scale on downstream processes � Cell culture titers of 4 g/L are now achievable for monoclonal antibodies: • Wurm F, “Production of recombinant protein therapeutics in cultivated mammalian cells,” Nature Biotechnology, 22(11) (2004). • Smith M, “Strategies for the purification of high titre, high volume mammalian cell culture batches,” presented at BioProcess International European Conference and Exhibition (2005). � New facilities are increasing bioreactor scale to 20+ m 3 to meet requirements of large volume products: • Lonza Portsmouth: 3 x 20,000 L (on-line) + 1 x 20,000 L (2006) • Genentech Vacaville CCP-2: 8 x 25,000 L (2009) � At 4 g/L, a 25,000 L bioreactor will yield 100 kg per batch � Increasing production scale and titers present challenges and opportunities for downstream process operation
Current approaches to managing high volume processes � At 4 g/L, a 25,000 L bioreactor yields 100 kg per batch • At a loading capacity of 20 g/L during capture chromatography, − 8 cycles on a 2 m (ID) x 20 cm (H) column (CV ~ 630 L) are required − At 15 CV buffer per cycle, 75,000 L of buffer are needed per batch per chromatography step � Current approaches based on maximizing value of existing conventional technology approaches (cf Smith*): • On-line dilution to reduce buffer storage requirements • Move to more rigid capture media to achieve higher velocities on chromatography steps • Multiple chromatography cycles (5-20) per batch • Load chromatography columns at/near break-through • Optimize UF steps to improve utilization of membranes � These approaches work, but may have a limited lifespan -> parallel track investment in novel technologies * - Smith, M, “Strategies for the purification of high titre, high volume mammalian cell culture processes,” presented at BioProcess International European Conference and Exhibition (2005)
Page 1 and 2: The Use of Disposable and Alternati
Page 3 and 4: Driving Forces
Page 5 and 6: The majority of manufacturing costs
Page 7 and 8: Technologies that • reduce capita
Page 9 and 10: Disposable products* exist across m
Page 11 and 12: Commercial product requirement tren
Page 13 and 14: Typical material requirements - cli
Page 15 and 16: 2004 bulk product requirements (kg/
Page 17 and 18: Examples of current “disposable f
Page 19 and 20: Membrane Adsorbers DNA removal ...c
Page 21 and 22: BIOFLASH 12 and BIOFLASH 80 Prepack
Page 23 and 24: Scale-up of recombinant protein sep
Page 25: Improved Handling and Ease of Use
Page 29 and 30: Potential obstacles to implementati
Page 31 and 32: Typical project costs - development
Page 33 and 34: Summary of COG estimates for a “t
Page 35 and 36: Extractables and leachates � Extr
Page 37 and 38: Future trends � Increased use of
Page 39 and 40: Thank you! BioProcess Technology Co

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