Perfusion is upstream processing which retains cells inside the bioreactor while continually removing cell waste products and media depleted of nutrients by cell metabolism. Fresh media is provided to the cells at the same rate as the spent media is removed. The most common means to achieve perfusion is the use of hollow fiber filtration.
Perfusion has been practiced in cell culture since the 1980s but with limited adoption due to complex or unreliable equipment and scale-up challenges associated with cell retention. Separate advances in cell line engineering, media composition, and bioreactor design generated magnitude-fold increases in titers for batch and fed-batch modes, thereby reducing the need for adoption of perfusion technology during that time.
Recently, however, the need for alternative manufacturing strategies that can boost efficiency and productivity while reducing costs has led to renewed interest in perfusion technology.
The introduction of the XCell™ ATF System, using novel alternating tangetial flow filtration, has changed the paradigm, making perfusion cell culture a viable platform for modern continuous processing.
As the provider of the broadest range of filtration technologies for bioprocessing, Repligen also offers KrosFlo® systems using traditional tangential flow filtration, as well as potent cell culture supplements and custom flow path assemblies.
Alternating Tangential Flow (ATF) Filtration
An award-winning technology, ATF allows the removal of spent media while keeping cells in culture. Applied using an XCell™ ATF device attached to a bioreactor, ATF minimizes cell shear and keeps cells in constant equilibrium with bioreactor contents. This results in faster cell growth at higher densities with higher productivity. Today, the XCell™ ATF device, in single-use or reusable format, is the leading perfusion device for mAb and rProtein production.
Tangential Flow Filtration (TFF) Systems
Turnkey, easy-to-use, cost-effective and scalable hollow fiber systems for tangential flow filtration (TFF), single-use filter modules and state-of-the-art hollow fiber membranes enable process and cost efficiencies in upstream perfusion. KrosFlo® KML 100 and KPS TFF Systems are fully integrated and ready to use out of the box, the systems include precise and reproducible control and documentation of all TFF processes.
Single-use custom flow paths
Ready-to-use connectivity between any bioreactor and the cell retention device facilitates the adoption of perfusion technologies. Defined through an engineering design process, Pro-Connex® Flow Paths are customized, configurable and complete assemblies for tangential flow filtration. The assemblies are sterile and manufactured in compliance with ISO guidelines in an ISO 7 clean room.
Potent cell culture supplements
Repligen developed and manufactures cell culture supplements that provide the benefits of serum supplementation while maintaining an animal-free process.
As a technology leader in bioprocessing, Repligen has compiled articles and essays from thought leaders on topics pertaining to continuous bioprocessing into easy-to-access e-books. These e-books summarize current thoughts on this paradigm shift in bioprocessing , the technical challenges, existing solutions and the promised opportunities.
The opinions expressed in these books are those of the authors and not of Repligen Corporation.
E-book Volume 2
Compiled by John Bonham-Carter, Repligen
Continuous Processing E-Book Volume 2
E-book Volume 1
Compiled by John Bonham-Carter, Repligen
Filtration Primer - WIP
How Alternating Tangential Flow (ATF) works - WIP
How Tangential Flow Filtration (TFF) works - WIP
XCell ATF from Repligen - WIP
Special Report on Continuous Bioprocessing: Upstream, Downstream, Ready for Prime Time?
by Angelo DePalma
BioProcess International, May 2016
Continuous Manufacturing: A Changing Processing Paradigm
By Randi Hernandez
BioPharm International, Apr 01, 2015
A Novel Seed-Train Process: Using High-Density Cell Banking, a Disposable Bioreactor, and Perfusion Technologies
by Benjamin Wright, Mike Bruninghaus, Mike Vrabel, Jason Walther, Neha Shah, Seul-A Bae, Timothy Johnson, Jin Yin, Weichang Zhou and Konstantin Konstantinov
BioProcess International, March 2015
Developing an Integrated Continuous Bioprocessing Platform: Interview with Konstantin Konstantinov
by Maribel Rios
BioProcess International, December 2012
A Brief History of Perfusion Biomanufacturing: How High-Concentration Cultures Will Characterize the Factory of the Future
by John Bonham-Carter and Jerry Shevitz
BioProcess International, October 2011