1 / 14

April 02 2008 Yannick Beauregard Queenie Chow Irena Doslo

April 02 2008 Yannick Beauregard Queenie Chow Irena Doslo. Diafiltration unit (DF-101) in Monoclonal antibody production . Background on diafiltration.

zev
Download Presentation

April 02 2008 Yannick Beauregard Queenie Chow Irena Doslo

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. April 02 2008Yannick BeauregardQueenie ChowIrena Doslo Diafiltration unit (DF-101) in Monoclonal antibody production

  2. Background on diafiltration • Is a technique that uses basic principles of filtration to completely remove, replace or lower the concentration of salts or solvents from solutions containing biomolecules • Uses permeable membrane to separate the components mainly based on size • Dilution and concentration • Dialysis, column-based gel filtration

  3. Intelligen., 1991

  4. Diafiltration unit (df-101) Intelligen., 1991

  5. Diafiltration Millipore Inc., 2003

  6. Design Considerations • Type of flow (tangential vs. direct) • Membrane selection • Type of diafilter modules • Diafiltration volumes • Continuous vs. discontinuous flow

  7. Tangential vs. direct flow • Direct Flow: • Large molecule trapped on membrane and forms gel • More susceptible to fouling • Flux rate decreases as volume filtered increases Millipore Inc., 2003 • Tangential Flow • Solute diffuses through the surface of the membrane tangent to the flow of the feed • Minimize build up of molecules – less fouling • Prevents rapid decline in flux rate Millipore Inc., 2003

  8. Membrane selection criteria • Primarily based on size of biomolecule • Molecular weight cut off (MWCO) of the membrane should be 1/3rdto 1/5th of the MW of the molecule to be retained • Typical MW of mAb: 150kDa => 30000 MWCO • Other considerations- surface chemistry • Membrane flux rate- time factor vs. product recovery • For protein separation: 30 LMH

  9. Types of diafilters • Flat sheet tangential flow • Hollow fibre • Tubular • Spiral wound Millipore Inc., 2003

  10. Continuous vs. discontinuous filtration • Continuous • Typically constant volume • Removal rate of salt = addition rate of water • Not the case in SuperPro model • Addition of WFI is at 1/3rd of the removal rate of salt (filtrate) in SuperPro • More suited for process scale- requires pumps • Discontinuous • Concentration and dilution cycles • Usually more feasible on a laboratory scale

  11. Diafiltration volume (SuperPro modifications)

  12. Final design • Hollow fiber cartridges • Membrane area needed • Mem. area = filtrate vol / (filtrate flux * process time) • 22.38 m2 with a 5% design consideration • From GE Healthcare services • ProCell ultrafiltration unit with 30000 MWCO pore size and seven 3.7 m2 membranes • UNIT NUMBER: • Stainless stain housing • Steam in place cartridges can be added GE Healthcare (2007) GE Healthcare (2007)

  13. Cost • Capital cost • Equipments • Membrane holder • Pumps, valves, piping • Type of instrumentation • Material cost • Membrane area • Water and chemical usage • Labour cost • Manual or automatic • In SuperPro, the design unit with 3 DV is $56000 GE Healthcare (2007)

  14. QUESTIONS? Thank you!

More Related