Zeta Plus™ Depth Filtration and Alternative Technologies for Cell Culture Clarification
Production of therapeutics proteins is continuously advancing to meet the latest demands of increased cell densities, improved productivity; greater flexibility; lower manufacturing costs with improved yields.
Once the fermentation is complete the first purification step which separates the cell and or cell debris from extracellular produced proteins is critical and must be robust. Typically Zeta Plus Depth Filtration, Tangential Flow Filtration (TFF) and Centrifugation are considered.
These technologies need to show several key performance attributes:
3M ™ Zeta Plus filter systems are available from 25cm2 (BC25) effective area capsules through to production scale 16” cartridges or to fully disposable3M™ Zeta Plus Encapsulated System (EZP).
Scale up experiments use constant flux (flow rate per unit area) which is subsequently scaled to full scale using similar conditions.
Tangential flow filtration systems can also be evaluated at small scale and data used to specify production size systems. In order to obtain accurate sizing for TFF systems, it is essential to use test filter devices with the same flow path length as will be used in production systems.
Centrifugation poses a more difficult scale up issue. In order to obtain accurate scale up information, the same g-force and flow path configuration device must be used.
Yields will have a direct impact on costs. Both TFF systems and centrifuges can limit product yield. Centrifuges of solids ejecting type can mean the solid dryness is 50- 70%, reducing product yield by up to 30-50%. TFF systems are limited by volume concentration factor (VCF) giving a total yield of 90%, or product yield loss is 10%. Zeta Plus depth filtration systems are direct flow and any residual product flushed through in a recovery wash post filtration. The disposable 3M ™ Zeta Plus Encapsulated System (EZP) has a hold up volume of less than 100ml for 11m2 effective filter surface area to provide high yields and low hold up volumes.
Zeta Plus depth filtration systems require only additional filter area to process larger volumes or take into account of fermentation variations and often used as the preferred platform technology.
TFF systems for cell separation are optimised and will need to be re-optimised for different processes and volumes. Centrifuge systems are also sized for specific process parameters. If batch size increases, centrifuge capacity cannot be added easily.