Boost your gene therapy and vaccine productivity

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+49 178 208 52 05

With our Continuous Bioreactor System

a Max Planck Institute Spinoff

CONTINUOS TUBULAR BIOREACTOR
(CTB)

Boost the productivity of your viral vaccine and gene therapy

processes using a smaller footprint

What is it?

The demand-supply gap for viral particles used in vaccines and gene therapies is increasing. It is estimated demand already outstrips supply by 5x. Part of this problem is due to manufacturing bottlenecks. 

Incremental increases in productivity with existing technologies will not be enough because current technologies have generally low production yields, are slow, and huge capital investments are required. New, efficient technologies are urgently needed.

We have developed a continuous tubular bioreactor (CTB) system that has the potential to tackle these issues. Our TCB is twice as fast as batch processes and has a much smaller facility footprint. 

Virus/plasmid

stock

3 cups

Flour

Continuous stirred tank reactor (CSTR)

for continuous cell growth

Virus harvest

Cell culture medium

stock

Tubular bioreactor (PFBR)

for continuous virus production

Drag the pointer over the image

Tubular segment

for virus propagation

​Our current ContiVir30 CTB system has been used successfully for the production of:

  • Influenza A virus

  • Adeno-associated virus (AAV)

  • Non-infectious coronavirus-like particles (VLP) resembling SARS-CoV-2

Our Approach to Continuous Virus Production

In the CTB system, suspension cells are continuously cultivated in a continuous stirred tank bioreactor (CSTR) operated as a chemostat. The cells are then mixed in-line with a virus/plasmid stock and fed into a tubular bioreactor segment, where the cells will flow in a one direction. Virus replication occurs along the tube and at the end the virus harvest is collected.

Also, thanks to the use of a plug-flow tubular bioreactor (PFBR) for unidirectional virus propagation and a defined virus residence time, the CTB system is the only truly-continuous bioreactor that not only enables virus production without risk of viral mutations, but also is capable of avoiding the negative impact of defective interfering particles.


 

Contivir technologies_v06.001.tiff
Production Performance with our CTB System

30×

volumetric output per month compared to a batch STR

(150x in 5 month of continuous operation!)

No titer loss

due to accumulation of DIPs as observed in batch systems

~2×

faster virus production than batch

demonstrated with a 1 L working volume CTB

that produces up to 30 L per month

Fully operational 1 L CTB of producing 30 L per month in our laboratories in Germany

Increase Production Capacity with a Smaller Footprint
Our CTB is Twice as Fast as Batch Systems

5E13 influenza virus particles

produced in

27 days with CTB system

vs.

50 days running 11 batches

Contivir technologies_v07.010 copy.tiff
Our CTB Minimizes the Risk of Virus Mutations
Contivir technologies_v07.011.tiff
Advantages

Our CTB system offers the following benefits compared to existing virus production technologies:

Increase capacity with existing footprint

  • Increases volumetric output up to 30× without increasing bioreactor size (15 L per month with a 0.5 L stirred tank). A 5 L STR coupled to a tubular segment can produce 150 L in one month.

Use the STRs you already have

  • The tubular module can be coupled to any existing STR in your lab/facility, transforming your batch process into a more efficient fully continuous system.

Scalability​

  • Our CTB can be used from lab to manufacturing scale, eliminating the need of changing/revalidating processes at larger scales. For example, a 1 L-scale CTB can provide 20-30 L per month which may be enough for pre-clinical or early clinical-phases. A 5 L-scale CTB can provide 150 L per month, and a 50 L-scale CTB can produce volumes of 1000 L or more.

​Single-use

  • Avoids impurity carry-over and cross-contamination.

  • Reduces CapEx and OpEx.

 

Simultaneous product manufacturing

  • Our CTB can produce different viruses simultaneously by connecting several tubular modules to one cell seeding reactor.

 

Higher virus titers

  • Our CTB avoids the accumulation of defective interfering particles that drastically reduce virus titers in batch processes and even semi-continuous systems (e.g. for influenza virus) and that makes the virus population genetically heterogeneous.

 

Future single-use industrial manufacturing made possible

  • Coupling a continuous tubular module to a 2000 L single-use STR can potentially produce up to 60 000 L per month, a product volume that today is only possible with stainless-steel systems.

 

Genetically stable virus production with minimal risk of mutations

  • Virus mutations can occur if viral particles stay in the bioreactor long enough and keep infecting new cells over days or weeks, as observed in other continuous bioreactors such as cascades of CSTRs. Our CTB system ensures higher virus homogeneity thanks to a unidirectional plug-flow in the tube that avoids back-mixing. The viruses produced along the tubular section cannot infect freshly produced cells entering the tube, avoiding the accumulation of genetically-aberrant viruses, greatly reducing the risk of mutations and producing a genetically stable and homogeneous virus harvest.