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Wave Biotech, LLC

300 Franklin Square Drive


Somerset, NJ 08873
USA: Toll Free (877) WAVE USA
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

The Wave Bioreactor Story


[ 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.

The Wave Bioreactor Story

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.

The Wave Bioreactor Story

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.

The Wave Bioreactor Story

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 Wave Bioreactor Story

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

The Wave Bioreactor Story

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

The Wave Bioreactor Story

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.

The Wave Bioreactor Story

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.

The Wave Bioreactor Story

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.

The Wave Bioreactor Story

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

The Wave Bioreactor Story

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

The Wave Bioreactor Story

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

The Wave Bioreactor Story

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

The Wave Bioreactor Story

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

The Wave Bioreactor Story

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

The Wave Bioreactor Story

Dr. Vijay Singh


The Wave Bioreactor Story

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


300 Franklin Square Drive
Somerset, NJ 08873
USA: Toll Free (877) WAVE USA
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