Processing pharmaceuticals and other processes including for production of monoclonal
materials requiring sterile conditions poses complex antibodies and viruses, insect cell culture and cGMP
and seemingly contradictory demands on mixing
technology. Equipment should avoid threats of con-
tamination while affording easy cleaning and simple
set-up and minimizing downtime for validation
and process engineering. In addition, mixers should
provide high output from a small footprint.
Vendors are meeting these challenges in a variety
of ways. A couple are particularly focusing on single-
use, i.e., disposable, mixing systems, which represent
one of the biggest growth areas.
For instance, GE Healthcare, Chalfont St. Giles,
U.K. and Piscataway, N.J., touts its Wave Bioreactor
single-use system as virtually eliminating the need for
cleaning and validation while avoiding cross-contami-
nation (www.ChemicalProcessing.com/articles/2006
/017.html).
Materials to be mixed only contact a pre-sterilized
disposable bag mounted on a special rocking platform
(Figure 1). Its motion induces waves in the fluid that
provide mixing and gas transfer.
The technology is used extensively in fermentation
April 2010 chemicalprocessing.com  26
CP1004_26_29_FLUIDS.indd 26
manufacturing. Scales range from bench-top systems
as small as 100-ml to production-scale units of 500-l
working volume.
However, the bag is quite complex due to the
need for aeration, inoculation, sampling and acid/base
addition. So GE now has launched a simpler single-
use bag for basic liquid mixing applications. The M
Bag does away with the need for a mixing tank or a
conventional mixer and, like the Wave Bioreactor, also
obviates cleaning, sterilization and validation. The bags,
which range in size from 20-l to 600-l, come with a
large screw-cap port for the easy addition of powders
and other solids, as well as fill and sample lines. They
also can be customized to suit an end users individual
processes. If larger-scale more-aggressive mixing is
required, GE offers versions with a built-in impeller.
Demand also is growing for more sensing tech-
nologies.The company already offers dissolved oxygen,
pH, carbon dioxide and oxygen sensors via miniature
fiber-optic microprobes. The ultimate goal here
would be to integrate every probe that you might want
3/26/10 3:07 PM
 in the bag to give all the required data in Wave motion
real-time. Going forward, there is a lot of
interest in RFID too, as the wireless format
makes everything much easier for operators, Figure 1. Rocking
movement of
says Rich Ferraro, senior product manager. platform induces
While originally developed to avoid cleaning and wave motion
in fluid in bags.
validation issues, today the technology has evolved Source: GE
into a route for flexible manufacturing. Remember Healthcare.
that it avoids large capex [capital expenditure] and the
hardware is generally off-the-shelf, too, he notes.
Ferraro believes that some innovations developed
for use by bioprocessing and pharmaceutical compa-
nies eventually will find their way into mainstream
chemical processing as the focus there also shifts to
more flexible manufacturing techniques.
In chemicals processing you run into issues that
you dont see in bioprocessing for example, the
different fluid viscosities and solids loadings as seen in respectively, a 100-l, 200-l or 500-l container with a
slurries. There is only so much shear force or energy magnetically driven impeller and an electronic drive
input that a disposable impeller or Wave format can unit (Figure 2). A variety of filter, connector and tub-
do in these situations before you run into performance ing options enable tailoring to a specific application
issues, he admits. Well need a more elegant yet cost- and environment, including sterile interfaces, from
effective solution going forward for the fine chemical fermentation to final fill. The single-use mixing sys-
or small molecule industries and some companies are tems also are available with stainless-steel carriers with
already working on this. and without external-heat exchange jackets.
He cites GEs collaboration with ILC Dover, Fred-
erica, Del., which has developed a novel mixing tech- Enduring solutions
nology based on an internal perforated septum moving Disposables arent the answer for all mixing chores
through the bulk fluid. This creates fluid jets capable requiring sterility, however. Some services call for
of mixing solutions with viscosities up to 100,000 cP.
Integrated system
Single-use units are in the offing. This type of technol-
ogy may find a home in the fine chemical and pharma-
ceutical industries in the near future, he adds.
Meanwhile, business developments are stirring up
the disposables sector. Merck, Darmstadt, Germany,
in late February announced its acquisition of Mil- Figure 2. Mixer
lipore, Billerica, Mass., for $7.2 billion. features mag-
netically driven
Like GE, Millipore has a strong focus on the impeller and
single-use market and its Mobius family of mixing electronic drive
systems delivers advanced technology for mixing system. Source:
Millipore.
pharmaceutical ingredients from intermediate to final
drug products and for preparation of process solutions
such as buffers and media.
Described by the company as the only single-use
mixers that are part of an integrated solution, Mobius
MIX100, MIX200 and MIX500 systems include,

27  chemicalprocessing.com April 2010

CP1004_26_29_FLUIDS.indd 27 3/26/10 3:07 PM

 RELATED CONTENT ON CHEMICALPROCESSING.COM
Disposable Equipment: Single-Minded Quest Continues, www.ChemicalProcessing.com/articles/2009/098.html
Disposable Equipment Earns Lasting Role, www.ChemicalProcessing.com/articles/2007/185.html
Disposable Equipment Makes Lasting Gains, www.ChemicalProcessing.com/articles/2006/017.html

Integrated system capabilities that only can be provided by heavier-

Figure 3. Ultrahygienic unit can be used to control the amount of shear a
material experiences. Source: Silverson Machines.
Rotating jet
Figure 4. Double rotation of jets produces mixing throughout a tank. Source:
Alfa Laval.
duty equipment. Innovations are emerging here, too.
Indeed, future success in pharmaceutical processing
depends on adopting such new technology, believes
Peter Matthews, technical manager of Silverson Ma-
chines, Chesham, U.K. and East Longmeadow, Mass.
He cites his firms UHLS ultrahygienic in-line mixers
(Figure 3) and Flashblend mixing system as examples.
One veterinary vaccine maker links two vessels
side-by-side with a UHLS in-line mixer, which is used
to pass product back and forth to achieve the required
level of mixing. Remember that for some customers it is
essential to know exactly how much shear a product has
been subject to something which can be very costly
in terms of time and equipment to establish, he notes.
Another long-term challenge is preventing loss of
a powders sterility when its being added to a mixing
vessel. With the Flashblend mixing system, the com-
pany has focused on eradicating dead areas, crevices
and any other hindrance that might lead to contami-
nation. Weve gone down to the nth degree on this
one with the result that there is no horizontal
pipework anywhere on the units.
A recent application at a U.S. pharmaceutical
company that manufactures a product contain-
ing a particularly toxic ingredient underscores the
systems value, he says. While degowning, opera-
tors were still at risk of coming into contact with
the toxic powder. The solution here was to put the
powder into a containment unit a bag which
is then introduced into the Flashblend via a total
containment valve. So the operator is completely
divorced from the ingredient and the product.
More and more [companies] are now actively look-
ing for solutions like this, both to apply health and
safety regulations and to handle raw materials and
products more effectively.
In the future, the location where mixing oc-
curs could change as the size of cleanrooms will be
drastically reduced, he believes. The cost to build
a cleanroom is phenomenal, so if you can minimize
the size of it, for example, by external mixing, you
can reduce the capex. And we are beginning to see
some technologies go this way. For example, we are

APRIL 2010 CHEMICALPROCESSING.COM 28

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 just opening a cleanroom for a ing full dissolution of powders. The For its part, Chemineer, Day-
company in France. Its very small company combats the problem with ton, Ohio, places an emphasis on
and the operator passes the powder a surprisingly simple solution. The cleanability. The company evalu-
direct to the vessel from outside Flex-Mix Instant inline batch mixer ates all components in its mixing
the area. In another example, an uses vacuum to draw powder under systems, from welds to impellers,
operator has a 5,000-l vessel in the the liquid, minimizing the amount to ensure mixing surfaces promote
technical area, with the clean room of air that enters the mix. free draining of liquids.
on the floor above for access.
Rotating jet nozzles are prom-
inent in the efforts of Alfa Laval,
Lund, Sweden, and Richmond,
Va. It offers mixers with two or
four such nozzles positioned un- Capture the Power: Buhler Aeroglide.
der the liquid surface at the top Product uniformity, efficiency, durability. Aeroglide conveyor
of a tank (Figure 4). A variable and fluid bed driers and coolers provide these critical elements
speed pump circulates liquid to
to chemical processors around the world.
be mixed through the tank in a
closed-loop system. The resulting
flow drives a gearing system in
the rotary jet mixer that causes Buhler Aeroglide
See us at Powder
the nozzles to rotate around 100 Aeroglide Drive, Cary NC 27511 USA & Bulk Solids 2010,
both the horizontal and vertical
Tel +1 919 851 2000, Fax +1 919 851 6029
sales@aeroglide.com, www.aeroglide.com/chemicals
booth 2539
axes. This double rotation pro-
duces mixing action throughout
the entire tank volume, report-
edly resulting in fast and efficient
mixing of the injected liquid, gas
or powder. The rotary jet mixer
also may be used for cleaning the
tank by feeding cleaning fluids
through the nozzles.
For Ekato Mixing Technol-
ogy, Lrrach, Germany, and
Ramsey, N.J., a long-term focus
has been on viscous systems. The
companys latest equipment is the
modular Paravisc system that can
handle viscosities from 1 mPas
to 1 million mPas. In addition,
it can be combined with baffles,
wall scrapers or independently
driven additional mixers (coaxial
or with eccentric two-shaft sys-
tems) as necessary.
Meanwhile, APV, a unit of SPX,
Charlotte, N.C., is working to keep
air from entering as powders are
added to liquid in a mixing tank.
The air can pose problems in pro-
cessing foods and beverages, among
other products, by causing foaming,
The solution behind the solution.
clogging and lumps, and hinder-

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