The Wave Bioreactor Story

Wave Biotech, LLC
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Telephone (732) 302 3100
Wave Europe Pvt. Ltd.

Unit 10, Matthew Hill Commercial Park,
Forge Hill, Kinsale Road, Cork, Ireland
Telephone +353 21 497 7014
www.wave-europe.com
Distributing Wave Biotech LLC products in the EU/EEA.
The Wave Bioreactor Story
www.wavebiotech.com
Wave Biotech, the parent company of Wave Europe, is a research-based company that
The Wave Bioreactor is a patented bioreactor for cell culture. In this device, cell culture is
manufactures innovative process equipment for the pharmaceutical and biotechnology
performed in presterile plastic bags. These bags called Cellbags are single-use bioreactors.
industries. Our focus is on developing single-use bioprocess equipment for operations
This design eliminates the need for cleaning, sterilization, and associated validation. The
traditionally performed in stainless steel tanks. Key products such as the Wave
gamma-radiation sterilized Cellbags reduce the risk of contamination due to equipment
Bioreactor , Wave Mixer , and Sterile Tube Fuser feature disposable contact materials
malfunction or operator error typical of traditional bioreactors such as stirred tanks,
that eliminate cleaning and validation, reducing capital and operating costs in
spinners, and hollow-fiber systems.
operations ranging from cell culture, media preparation, buffer dissolution, and
thawing, to patient-specific cell therapy in hospitals. These unique, patented devices can
The Wave Bioreactor was developed in 1996, and commercial units have been in operation
be installed and commissioned quickly, dramatically reducing the time-to-market for
since 1998. Hundreds of units are in use worldwide, utilizing a wide variety of cells including
biologicals. Our products are in use with hundreds of companies worldwide, both for
CHO, NS0, hybridomas, HEK293, insect/baculovirus, adenovirus, T-cells, plant, and
R&D as well as commercial applications.
primary human cell lines.
[ copyright 2005 by Wave Europe Pvt. Ltd. ]

[ Cover Art: Illustration from Wave Bioreactor US patent filing ]
Design: Inc Design www.incdesign.com

[ by Vijay Singh Ph.D. ]
An Idea Is Born
The Wave Bioreactor was conceived in August 1996 on a long
Cathay Pacific flight from Sydney to New York. I was returning
from attending the International Biotechnology Symposium in
Sydney, Australia, where I had presented a talk on optimizing the
scheduling of bioprocess facilities. One of the lectures I attended
was a talk by the eminent MIT biotechnologist, Dr. Danny Wang. He
talked about the industrial applications of cell culture and how the
technology of the day was completely unsuitablewe used stirred
tanks that destroyed cells due to fluid shear; aeration was done by
bubblingsomething everybody agreed was detrimental. Finally,
even though cell culture media was filter-sterilized, the industry still
sterilized empty tanks with steam.
The issues he raised struck a chord. I was in charge of large-scale
cell culture facilities at Schering-Plough, and I was keenly aware of
these bioreactor design problems. I had another issue to add to his
list. In industry, we were spending weeks to clean, prepare, sterilize,
and maintain the cell culture tanks.
My own studies showed that we were spending at
A Concept Takes Shape
week of operation. And this did not even include
On my return to the States, I did a literature search
ing with contaminations or product changeovers.
ing useful. The design problem that needed to be
least one week in prep and maintenance for every
on scalable single-use bioreactors, but found noth-
the time spent qualifying new equipment or deal-
solved was how to mix and aerate without the tra-
These were major events, involving cleaning,
ditional stirrer and bubbler. There were some static
replacement of many contact parts, sampling for
gas-permeable culture bags, but these were limited
cleaning validation, and multiple sterility trials. A
to small volumes due to the fact that oxygen had to
requalification after contamination or product
be introduced by diffusion through the bag wall,
changeover in a bioreactor tank resulted in weeks
and this surface area was very limited and clearly
of downtime.
could not be scaled up beyond a few liters. In addi-
Having already seen the movie on the plane, I
tion, there was no means of mixing the contents of
started thinking about a new way of doing cell
the bag and the cells would settle and soon be
culture. It had to be disposable, easy to operate,
starved of nutrients and oxygen.
and scalable to at least a 500 liter culture volume.
The ideal device would be a bag. Bags were
The solution occured to me following a tragic acci-
storage and transport of biologicals, and so materi-
the sea off the coast of Long Island. Reading The
already
being
used
extensively
for
dent. In July 1996, TWA Flight 800 had fallen into
the
New York Times on September 6, I was surprised to
al compatibility would not be of great concern.
learn that the salvage crews were concerned that an
And unlike molded rigid devices, a bag offered the
impending storm would disturb the debris 140 feet
potential for a very low cost bioreactor.
The shape of a Cellbag20L has the exact dimensions of a standard

American cafeteria tray! The first bag holder was made using a
borrowed cafeteria tray. Since so much data on mixing,
mass transfer, and cell growth was developed using this
prototype, it became the standard geometry. All larger
systems are multiples of this original geometry.
Figure 1.
Inflated plastic bag forms
disposable
cultivation
chamber
The Schematicaof
the Wave
Bioreactor
concept
Cell
Culture
Media
wave
Rocking
Motion
Figure 2.
September 26, 1996, the first Wave Bioreactor
Inflated plastic bag forms

a disposable cultivation chamber
Cell
Culture
Media
wave
Rocking
Motion
Wave action creates large turbulent

surface for oxygen transfer
Rocking
Motion
Rocking
below
Motion
wave
Wave action creates large turbulent

surface for oxygen transfer
Wave action
sweeps up
cells and
prevents
settling
Wave action
the
was the breakwave ocean surface! This
to generate waves with each rock. Furthermore, it
down, we could certainly use waves to mix nonin-
motion, oxygen was being transferred into the liq-
throughif waves could
sweeps up
cells and
disturb
debris
prevents
settling
that far
became apparent that, due to the turbulent wave
vasively in a bag. I quickly constructed a tray that
uid phase from the headspace. This gave me the
could be rocked. By placing a flat pillow-shaped
second essential facet of a bioreactoraeration.
bag on this tray and rocking the tray back and
Schematically, the idea is shown in Figure 1.
forth, we could make waves. Unfortunately, the
It was vital to try to see if cells could grow in a
bag soon broke, but we discovered that if we inflat-
rocking bag. I constructed a machine out of an old
ed the bag and secured it to the tray, we essentially
gel rocker and had a bag made by a local blood bag
created a rigid object that was quite strong. If this
manufacturer. The machine was first run on
bag were partially filled with liquid, it was possible
September 26, 1996, and is shown in Figure 2.
Figure 3.
Tracer photographs showing mixing patterns
The mixing studies showed that the wave system
was a remarkably efficient mixer. Typically, it took
only 5-10 seconds to achieve homogeneity.
Although the rocker destroyed itself within a few
liquid capacities. The mixing studies showed that
days, I had achieved good cell growth.
the wave system was a remarkably efficient mixer.

Typically, it took only 5 to 10 seconds to achieve
Having established that the idea could work, I set
homogeneity. Much of this characterization work
about characterizing the system in terms of its
was done by college interns who were assigned to
mixing and oxygen transfer capabilities. The next
me to learn about industrial biotechnology.
rocking machine was powered by alternating
Measuring the oxygen capabilities of the system
pneumatic pistons and very robust. I had custom
posed a greater challenge. In 1997, there were no
bags made by various suppliers. These had
dissolved-oxygen probes sufficiently small or flex-
sampling ports and filtered vents for inflation and
ible to fit inside a bag. In order to measure oxygen
venting. I devised a method to measure mixing
transfer, I needed a fast dynamic response, as the
using fluorescent dye injections and then used a
classic technique was to introduce nitrogen to
high-speed video camera to follow dispersion of
reduce the dissolved oxygen to zero and then
the dye. By calculating the movement from frame
switch to air. The rate of increase in dissolved
to frame in the video, I was able to determine the

optimal rock angles, geometry, rocking speed, and
oxygen is proportional to the oxygen transfer rate.
acceleration profiles. A sample sequence of the
Searching the medical literature I came across a
mixing photos is shown in Figure 3. The tracer
technique that used quenching of a phosphorescent
technique proved to be invaluable when we started
dye to optically determine the dissolved oxygen
working with larger systems of 100 and 500 liter
concentration. The experiment involved adding the
The original oxygen transfer studies used

oxygen-sensitive phosphorescent dyes.
With the development in 2004 of an insertable fast-responding
optical dissolved oxygen probe it became possible
to easily measure oxygen transfer rates in
Wave Bioreactors.
dye to liquid in the bag and measuring the oxygen
The first device we had tried was a single-axis
probe that measured reflected phosphorescence
were taped onto the rocker tray. Many early
content noninvasively using a rented fiber-optic
rocker with a side-to-side motion. The culture bags
through the clear plastic bag wall. This technique
experiments failed due to bag breakage. The
allowed us to rapidly characterize the capabilities
rocking motion caused the bags to flex
of the bioreactor at different rocking speeds,
continuously, and the plastic films developed
angles, and acceleration profiles. The experiment
fatigue cracks and ultimately leaked. We experi-
and sample dynamic response is shown in Figure 4.
mented with many different films and methods of
The data obtained in this manner showed that a
securing the bag to the tray. Finally, we developed
necessary to support 6 to 8 million cells/ml.
ute the stress; this bag could function reliably for
Wave Bioreactor could provide the oxygenation
a bag with two rigid plastic support rods to distrib-
Typical
DO DO
Response
Typical
Response
80 80
70 70
DO % Sat.
DO % Sat.
60 60
50 50
40 40
30 30
20 20
10 10
0
500 500
10001000
15001500
Seconds
Seconds
Figure 4.
Dynamic Oxygen Measurement
several weeks. We experimented with bag geome-
the rock stroke. Using computer simulation mod-
gen transfer yet minimized foaming.
angle and speed. Experimental work had to be
try and arrived at a bag design that gave good oxy-
els, it was possible to predict the effects of rock

done to evaluate the effect on foaming.
We looked at multiple-axis rockers. These were
Determining the best tilt angle, speed, and the
capable of imparting circulatory motion, but the
acceleration profile for the rocker took the rest of
slightly better mass transfer and mixing were not
1997, but we finally had a system capable of 100
worth the increased complexity, especially on a
liter culture volume that barely foamed.
larger scale. Other experiments with paddles and

devices to bend and flex the bag were not very suc-
In September 1997, at the ESACT conference in
cessful due to rapid bag breakage. The single axis
Tours, France, I presented a paper on what was to
rocker eventually became the device of choice.
become the Wave Bioreactor. The data were

expanded into a paper that appeared in
By mid-1997, I had sufficient mass transfer
Cytotechnology. In 1998, I presented data at 100
and mixing data to start testing the system with dif-
liter culture scale at the Cell Culture VI conference
ferent cell lines. Experiments were performed at 1
in San Diego. The San Diego data compared side-
and 10 liter culture volumes. The early cell lines
by-side runs at 100 liter volume in the Wave
tested were CHO and NS0. We also did Sf9 insect
Bioreactor and a stirred tank using the same cell
cells and even infected HEK 293 cells to produce
inoculum and media. Results showed that the cell
recombinant adenovirus. We got good cell growth
growth and productivity were identical. The cell
almost right from the beginning, but foaming was
line used was NS0, producing a humanized anti-
a big problem. Refining the bag design to minimize
body in serum-free media.
creases and increasing inflation pressure helped a
Other innovations in 1997 and 1998 were: 1) the
lot, but the real key was the acceleration profile. To
development of a sampling fitting that allowed the
reduce foam, it was necessary to initially accelerate
Wave Bioreactor to be sampled in the lab and did
the bag very quickly; once the bag passed the mid-
not require a laminar flow hood; 2) a tiny (120um
point, it was necessary to decelerate the bag at a
diameter) dissolved-oxygen probe that could be
controlled rate to avoid a big splash at the end of
One of the quirks of the Wave Bioreactor is that unlike a

stirred tank it becomes more efficient with increase in scale.
Small volumes need a high tilt angle while larger ones only
tilt a degree or so to achieve the same mixing and
oxygen transfer rates.
used to monitor dissolved oxygen in the culture in
The next stage was to make this system commer-
relief valve that could maintain constant internal
assigning rights to Schering-Plough, as was
real time; and 3) a disposable exhaust pressure
cially available. I had filed patent applications
bag pressure regardless of airflow rate.
required by my employment contract. Schering,

however, was not interested in patenting the
technology. After some negotiation, we came to an
agreement to transfer the intellectual rights back to
Commercial Realization
me. I owned a holding company called Panacea
By mid-1998, it was clear that the Wave Bioreactor
Solutions that I used to develop other inventions,
could grow a wide variety of cells. It was easy to
mostly related to aviation, and all of the Wave
operate and solved many of the issues raised in the
Bioreactor intellectual property was transferred to
original 1996 lecture by Dr. Wang. It had very low
this company in 1998 and remains there today. The
shear, since it did not use any kind of high-speed
patent for the method was eventually granted in
rotating mixer; the aeration was from the head-
2001 and extended later to perfusion in another
space and introduced very few bubbles. There was
patent granted in 2003.
no need to sterilize or validate the device before
use. And for me personally it eliminated the need
During this time, I met, through a mutual friend,
for cleaning and maintenance, and was so easy to
Mr. Marcel Roell, who owned a small equipment
use that I could train a summer intern with no
fabrication facility in Switzerland, and he agreed to
previous cell culture experience to run a 100 liter
manufacture commercial-grade rocking machines
culture within one or two days.
Although the Wave Bioreactor was designed mainly for suspension

cell culture, it is also used successfully for many attachment cell lines.
Even primary lines such as HeLa and vero are grown.
These applications require microcarriers in the Cellbag.
A variety of microcarriers are available, most of which can be
supplied presterile in the Cellbag.
for market evaluation. I designed the culture bags,
wide, while Wave Biotech AG under Mr. Roell
by various subcontractors. I had inquiries from
countries. Technology was licensed to each from
now trademarked as Cellbag , and had them made
would service Switzerland and certain European
several researchers who had read my papers and
Panacea Solutions, my holding company for
were interested in trying a unit. We got three
patents, trademarks, and other intellectual
companies in the United States to agree to test the
property related to the Wave Bioreactor.
unit. After some months, we evaluated the feed-
Commercial production of the SYSTEM20 began
back. The first company never opened the box. The
in mid-1999. This benchtop machine could, using
second liked it, but needed 100 liter capacity
various sized bags, handle culture volumes from
years later, they purchased several SYSTEM200
100ml to 25 liters. By late 2004 more than 1000 of
machines. The third company sent us a purchase
these units had been sold.
order for 10 machines. We had a product!
The relationship between Wave Biotech LLC and
Wave Biotech was formed in June 1999. Two
Wave Biotech AG worked fairly well until 2003.
companies were created to manufacture, market,
Since early 2004, Wave Biotech LLC has assumed
and distribute the Wave Bioreactor. Wave Biotech
worldwide responsibility for further development
LLC, under my direction, would function world-
and manufacture of the Wave Bioreactor.
Market Acceptance
tions published by a number of researchers slowly
Despite the excellent performance of the Wave
a viable system for many cell lines and applica-
convinced the industry that the Wave Bioreactor is
Bioreactor, it was not an instant success. People
tions. Published work included results with cells in
were skeptical that such a simple and low-cost
suspension, attachment on a variety of microcarri-
bioreactor could rival the complex and expensive
ers, virus production, plant cell culture, yeast,
stirred tanks. We were lucky that there were a
human and primary cells, and even the traditional
number of enlightened scientists and engineers
province of the stirred tankE. coli in the Wave
who, early on, saw the potential savings a truly
Bioreactor. Copies of these studies are available on
disposable scalable bioreactor could provide and
the www.wavebiotech.com website.
ordered machines to test with various applications.
In the three years from 1999 to 2002, the Wave
At the ESACT conference in 1999, I presented,
Bioreactor became established technology and was
along with several co-authors, our work on using
used in mainstream research and manufacturing
the Wave Bioreactor with microcarriers for
operations. The cutting-edge applications then
attachment-dependent cells and applications with
shifted to ex-vivo cell therapy, high-density
myelomas and even plant cells. This and many
perfusion culture, and larger-scale bioreactors.
other scientific papers, conferences, and presenta-
One Wave Bioreactor customer runs thirty 5 liter cultivations

simultaneously using 15 Wave Bioreactors. Two SYSTEM200
units are used to provide inoculum. The facility only employs two
people to run this entire operation.
Figure 5.
Commercial System200EH (100 Liter Culture Volume)
The design evolved from a bag strapped to a sheet of

plywood to the sleek stainless steel SYSTEM200EH units
with linear electric drive motor and touchpanel introduced
in 2002.
Larger Scale Systems
major overhaul after just a year of operation. In
As far back as 1997, work had begun on larger
redesigned using linear electric motors. Although
2002, the SYSTEM200 sold in the U.S. was
scale systems. The first prototype units were made
these units were much more expensive to build,
of plywood on aluminum frames, the bags were
they had no gears and only one moving part. The
held down by straps, and pneumatic pistons pro-
units could essentially run forever. Unfortunately,
vided the rocking motion. The early experiments
Wave Biotech AG focused on small-scale applica-
were quite successful but the bag film proved to be
tions, which meant that the obsolete geared motor
too brittle and prone to breakage within days. This
technology continued to be sold in Europe until
problem was only satisfactorily solved in 2000,
2004, when Wave Biotech LLC took over the
when we switched to using new plastic films that
European Wave Bioreactor market.
had much better fatigue strength.
More than a hundred SYSTEM200 units are now
SYSTEM200 was shown in 1999 at ESACT
in use worldwide. The simple scale up to 100 liter
with a culture volume of 100 liters. Several
culture from smaller Wave Bioreactors makes the
SYSTEM200s were sold in 2000. These units used
transition easy. Units are used for R&D, manufac-
geared motors and it became rapidly apparent that
turing, and inoculum propagation. The design
the back-and-forth motion of the Wave Bioreactor
evolved from a bag strapped to a sheet of plywood
was too severe on the gears and the units needed
to the sleek stainless steel SYSTEM200EH units
10
Figure 6.
Early 1200 Liter Wave Bioreactor
The first 1000 liter Wave Bioreactor was quite primitive and
was used in a temperature-controlled hot room as
shown in Figure 6. Note the duct tape holding the bag to
the rocker!
with linear electric drive motor and touchpanel
antibody production! The early large-scale Wave
nology led to a huge spurt in large-scale applica-
ature-controlled hot room, shown in Figure 6.
introduced in 2002 (see Figure 5). The new tech-
Bioreactor was primitive and was used in a temper-
tions, especially for manufacturing.
The large units posed many initial problemstheir
pneumatic rocking mechanism generated too much

foam and the bag cracked easily. Although the con-
Even Larger Systems
cept had been demonstrated, the unit was not ready
One of the goals of the Wave Bioreactor develop-
for commercial use. Research and development
ment was to produce scalable technology. The
took until 2003 before a commercial machine was
objective was to achieve a culture volume of at
possible. Many critical problems had been solved:
least 500 liters. In 1998, the first attempts were
1) improved plastics made bigger bags possible; 2)
made at this scale. The first two tries failed due to
linear motors allowed reliable rocking mechanisms
mechanical problems, but the third run was a
and programmed motion profiles; and 3) better
resounding success. NS0 cells were grown in a
knowledge of wave fluid dynamics made it
1200 liter bag in parallel with a 1000 liter stirred
possible to make a bag holder with sloped ends.
tank. Inoculum for both bioreactors was grown in a
This innovation improved wave action and reduced
series of small Wave Bioreactors. The results with
stress on the bag. A new concept (patent applied for
580 liters of culture in the Wave Bioreactor showed
in 2004) was to operate the unit in resonance. The
identical performance in terms of cell growth and
11
resonant wave motion provided equivalent mixing
The first sensor developed was for dissolved
continuous rocking.
polarographic probe used for medical purposes.
and mass transfer with 60% less energy input than
oxygen. It was derived from an extremely thin

The probe was adapted to a special fitting on the
Currently, the largest Wave Bioreactor offered is
Cellbag that permits the probe to be removed,
the SYSTEM1000, shown in Figure 7. This has a
recalibrated, and reused. This probe has been used
maximum culture capacity of 500 liters. Units are
since 1998 and has been invaluable in monitoring
currently in place in the U.S. for production of
oxygen concentration. It does have the drawback
clinical trial materials.
of all polarographic probesit takes a long time to

stabilize and is prone to drying and sudden failure.
Development of Sensors
In 2004, a new fiber-optic oxygen system replaced
Mixing and aeration are fundamental requirements
sive fiber-optic technology is much more reliable
the original polarographic one. This new noninva-
for a bioreactor, but sensing is just as important.
and has the potential to be utilized for many other
Key sensors are needed to measure dissolved-oxy-
measurements such as pH and dissolved CO2.
gen, temperature, and pH. Obviously, the metal

sensors used in stirred tanks were not suitable for
For perfusion operations, it is essential to control
cal task in the enhancing the usefulness of the
just a matter of measuring and controlling the level
the volume in the bioreactor. For a rigid tank this is
use in bags and so research on sensors was a criti-
in the tank. However, it is quite difficult to judge
Wave Bioreactor.
The website www.wavebiotech.com has up-to-date

information on new developments, technical literature,
and trade shows where the Wave Bioreactor is exhibited. All the
presentations and papers mentioned here are
available for download.
12
Figure 7.
Commercial System1000EH (500 Liter Culture Volume)
Currently, the largest Wave Bioreactor offered is the

SYSTEM1000. This has a maximum culture capacity of 500
liters. Units are currently in place in the U.S. for production
of clinical trial materials.
the volume in a bag, and so a weight-monitoring
local shear. The Wave Bioreactor, on the other
under the bag holder so that it is not influenced by
move with the liquid, almost like a hot-air balloon
instrument was developed. This device mounts
hand, has almost negligible shear, since the cells
the weight of the rocker mechanism. The sensors
in the wind. This makes scale up easy. The geome-
are moment compensated so that a steady weight
try of the system is designed so that the oxygen
reading is obtained for control regardless of the
transfer rate is constant at all scales. It is only nec-
rocking motion.
essary to set the correct rocking angle and rate to
get the desired oxygen transfer without excessive

foaming.
Scale Up
A critical aspect of any bioreactor is the ability to
The Wave Bioreactor is a momentum machine.
determine the operating conditions necessary at a
Tilting the rocker causes gravity to accelerate
larger scale that are identical to those at a smaller
the wave. The larger the amount of liquid, the
scale, at least as far as the cells are concerned. This
greater the momentum. This is why, paradoxically,
is the essence of scale up.
Wave Bioreactor scale up becomes easier as the
volume increases. Tables have been established,
With stirred-tank bioreactors, scaleup is a chal-
based on extensive simulation studies, oxygen
lenge. As the tank gets larger, the distribution of
transfer experiments, and actual cell culture, that
shear in the tank becomes greater, with very high
provide the corresponding rock angle and speed for
shear rates near the impeller. Cells circulating into
different Cellbag sizes, from 100ml to 500 liter
the impeller zone are often damaged due to high
culture volumes.
13
Design for GMP
usage. More than 10 companies currently use the
The Wave Bioreactor was designed for Good
ufacture of human therapeutics with several more
Wave Bioreactor in licensed facilities for the man-
Manufacturing Practices (GMP) use from the very
in various stages of clinical trials.
beginning. Bag materials and quality control
procedures were chosen to meet all regulatory

requirements. Components such as filters and
Perfusion for
High Productivity
sampling connectors were selected, and validation

documents were published to assist users in quali-
Perfusion is an attractive operation for high
fying the equipment.
productivity. By retaining the cells in the reactor, it
is possible to get the high cell densities needed for
With a disposable system, the amount of validation
gene therapy or to produce large amounts of
and qualification work becomes almost trivial.
soluble proteins. The Wave Bioreactor can be used
Each Cellbag comes with a certificate of compli-
with patented internal cell-retention filters or with
ance, and in most cases validation is simply a mat-
external circulation devices.
ter of filing the certificate. Obviously batch and

even product changeovers are nonevents as they
A paper by Pierce and Shabram in Bioprocessing
simply involve replacing the Cellbag.
Journal, July/August 2004, showed the potential of
such a system. The authors reported that a single
Capabilities for customizing and tracking product
Wave Bioreactor SYSTEM1000 operating at 500
changes were implemented early to support GMP
Researchers have grown all kinds of cells in the

Wave Bioreactor. garlic, ginseng, pine tree embryos, human
stem cells, yeast, E. coli, and even nematodes.
14
liter culture volume in perfusion produced 150
bioreactors, and these machines must be simple to
remarkable feature of this operation is that Wave
Wave Bioreactor is an ideal manufacturing plat-
grams of protein in 24 days of operation. Another
operate and not prone to cross-contamination. The
Bioreactors were used for the entire inoculum
form for developing such technologies.
propagation. The cell culture facility was simply an
Other applications include the integration of prod-
empty clean room with several Wave Bioreactors.
uct recovery and separation in the cell culture bag,

and low cost systems for vaccine production that
offer closed system integrity without the need for
The Future
highly skilled labor.
Predicting the future is always dangerous. Who

could have predicted in 1996 that a bag could be
I developed the Wave Bioreactor to address my
actors costing five times as much? While better
that would grow the cells I needed for my work,
needs as cell culture scientist. I needed something
used as a bioreactor and would replace tank biore-
without spending most of my time fixing gaskets,
designs will evolve, the intrinsic simplicity of the
changing seals, sterilizing, and validating. With the
Wave Bioreactor will ensure it remains a useful
Wave Bioreactor, anyone can grow cells and get on
device for many applications in the years to come.
with their real jobmaking these cells do useful
New applications continue to push the technology.
things. The future of the Wave Bioreactor will
For example, the needs of cell therapy and stem
depend largely on our continued ability to
cell research require large quantities of cells. These
understand and address the changing needs of cell
need to be grown in a large number of individual
culture. We are listening.
15
Dr. Vijay Singh

Dr. Vijay Singh is the president and founder of Panacea Solutions, Inc. and Wave Biotech.
He has a doctorate in biochemical engineering, and his thesis work was on mixing and
mass transfer in very large bioreactors. He has published extensively on bioreactor design
and operation. He was with Schering-Plough for many years and was responsible for the
development and manufacture of interferon alfaone of the first genetically engineered
drugs to be licensed. Since 1999, he has focused on the Wave Bioreactora single-use
scalable device for cell culture.
16
Wave Biotech, the parent company of Wave Europe, is a research-based company that
The Wave Bioreactor is a patented bioreactor for cell culture. In this device, cell culture is
manufactures innovative process equipment for the pharmaceutical and biotechnology
performed in presterile plastic bags. These bags called Cellbags are single-use bioreactors.
industries. Our focus is on developing single-use bioprocess equipment for operations
This design eliminates the need for cleaning, sterilization, and associated validation. The
traditionally performed in stainless steel tanks. Key products such as the Wave
gamma-radiation sterilized Cellbags reduce the risk of contamination due to equipment
Bioreactor , Wave Mixer , and Sterile Tube Fuser feature disposable contact materials
malfunction or operator error typical of traditional bioreactors such as stirred tanks,
that eliminate cleaning and validation, reducing capital and operating costs in
spinners, and hollow-fiber systems.
operations ranging from cell culture, media preparation, buffer dissolution, and
thawing, to patient-specific cell therapy in hospitals. These unique, patented devices can
The Wave Bioreactor was developed in 1996, and commercial units have been in operation
be installed and commissioned quickly, dramatically reducing the time-to-market for
since 1998. Hundreds of units are in use worldwide, utilizing a wide variety of cells including
biologicals. Our products are in use with hundreds of companies worldwide, both for
CHO, NS0, hybridomas, HEK293, insect/baculovirus, adenovirus, T-cells, plant, and
R&D as well as commercial applications.
primary human cell lines.
[ copyright 2005 by Wave Europe Pvt. Ltd. ]

[ Cover Art: Illustration from Wave Bioreactor US patent filing ]
Design: Inc Design www.incdesign.com
Wave Biotech, LLC

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Wave Europe Pvt. Ltd.

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Telephone +353 21 497 7014
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Distributing Wave Biotech LLC products in the EU/EEA.
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