Pilot to Commercial scale Viral Vector Manufacturing:

Artemis Biosystems

11 Tileston Street, Boston, MA 02113

Tel: 617-674-2747

info@artemisbiosystems.com


Leadership

Management Team

  • Maurizio V. Cattaneo, PhD: Founder and CEO
  • Remco A. Spanjaard, PhD: Founder and CSO

Board of Directors

  • Maurizio V. Cattaneo, PhD: Founder and CEO
  • Remco A. Spanjaard, PhD: Founder and CSO
  • Jean-Marc Pandraud
  • Scott H. Gillis

Scalable viral vector manufacturing with VHU™ Perfusion

The Problem: Cell Factories are inefficient for large scale manufacturing of viral vectors.

Bluebird bio is working with Artemis Biosystems to evaluate its filtration technologies as part of its ongoing viral vector process development efforts.


Viral vector and vaccine production from adherent mammalian cells is typically performed using cell factories  in a Scale Out fashion, i.e. by adding additional cell factory units to meet viral vector demand is cost prohibitive when running at commercial scale (eg. >200L).  

The Solution: Scalable Production of Viral Vectors using the VHU™ Perfusion System

 

Alternatively, the use of suspension cells to produce viral vectors offers a Scale Up solution which is gaining traction in the industry. Suspension cells are grown to high densities in perfusion bioreactors which allow orders of magnitude greater viral titers and the continuous removal of toxic compounds.  Acoustic-based perfusion devices such as BioSep® are limited  to R&D production scales.  In addition,  the current ATF perfusion systems cannot be used for production of viral vectors because they do not allow the viral vectors (eg. Lentiviral (LV) or Adeno Associated Virus (AAV) to permeate through the hollow fiber membrane (see caption "Competitor ATF system" in the figure below entitled "% Lentiviral Recovery at Harvest").  


Artemis Biosystems has developed a scalable production system based on  VHU™ perfusion technology (Patent Pending) to produce clinical or commercial quantities of viral vectors from mammalian cells in suspension culture such as HEK293 or HeLa in either a transfection or stable producer cell line mode. VHU™ Perfusion increases viral vector production by at least 1-2 orders of magnitude (ISBiotech, March 5-7, 2018). This translates in  100% viral permeation efficiency compared to zero for the control ATF which uses hollow fibers (see Figure below).  Artemis Biosystems supports all gene therapy and vaccine-related needs from pilot to commercial scale by offering VHU™ Perfusion technology which provides:


  • 100% efficiency harvesting virus from bioreactors
  • Fast processing times for quick media changes
  • Integration of media exchange and viral harvest in a single step
  • Closed, disposable Virus Harvest Units derisk production runs
  • Scalable with bioreactors ranging from 2L (VHU2™) to 2000L (VHU2000™) 
  • Customization upon request

"Biosep®" is a registered trademark of Applikon Biotechnology

VHU2™ MODEL SPECIFICATIONS

Artemis Biosystems is the first company to offer disposable Virus Harvest Units (VHU™) specifically designed for connecting via sterile connectors with either HyPerforma™ or Xcellerex™ Single Use Bioreactors ranging in size from 50L to 2000L to produce viral vectors from suspension cell lines.  VHU™ revolutionizes processing time and viral permeation efficiency to support all gene therapy and vaccine-related needs from pilot to commercial scale: • 100% efficiency harvesting virus from bioreactors • Fast processing times for quick media changes • Integration of media exchange and viral harvest in a single step • Closed, disposable Virus Harvest Units derisk production runs • Scalable for use with bioreactors ranging from 2L (VHU2™) to 1000L (VHU1000™) in perfusion mode • Customizable upon request


SPECIFICATIONS AND PERFORMANCE

  • Length of 60 cm and total surface area of 527 cm2
  • 100% efficient permeation of lentivirus while fully retaining producer cells
  • Gamma-irradiated for sterility
  • Patent Pending


"XCellerex®" is a registered trademark of General Electric Corporation.

"HyPerforma" is a registered trademark of ThermoFisher. 


Contact us if you want to know more about VHU™

Please get in touch by sending us an email at info@artemisbiosystems.com, or call us at 617-674-2747 to discuss how  VHU™ can solve your viral vector production scale up problems from pilot to commercial scale

Progress in Viral Vector Manufacturing

Viral Vector Production using adherent cells is on its way out!

  • One of he biggest obstacles facing the gene therapy industry is lack of scalable manufacturing of viral vectors. CMOs are currently using legacy adherent cell technology using e.g. cell factories which can be scaled OUT but NOT be scaled UP. This causes enormous amounts of technical difficulties and cost to gene therapy companies. The solution: viral vector-producing cells grown in suspension and the VHU™  Perfusion system. With the VHU™  perfusion system it is possible to scale UP up to 2000L of cell suspension culture in both transient transfection mode and/or stable/inducible producer cell lines which pump out viral vectors in a semi-continuous fashion (Manceur et al. 2017, Scalable Lentiviral Vector Production Using Stable HEK293SF Producer Cell Lines, Journal of Gene Therapy Methods, Volume 28 Number 6, Pages 330-339). 


  • For suspension cell lines using transient transfection, the VHU™  Perfusion System is initially used to increase the viable  cell density by 1-2 orders of magnitude (1E07-1E08 cells/mL)  in a "Process Intensification" mode, after which the cells are transfected with Polyplexes (PEI:DNA complexes) under a batch mode for a few hours to a day, and then the bioreactor is returned to Perfusion mode to harvest the viral vector (such as LV or AAV) in a semi-continuous mode for a few days post transfection (3-5 DPT) (Ansorge et al. 2009, Development of a scalable process for high-yield lentiviral vector production by transient transfection of HEK203 suspension cells, The Journal for Gene Medicine, Volume 11, Pages 868-876). 

Download VHU™ Brochure

ArtemisBiosystemsBrochureVHU2018 (pdf)

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