High Quality Materials
For High Quality Bioreactor Systems
for High
Quality Bioreactor Systems
Applikon Biotechnology
BIOREACTOR SYSTEMS
High Quality Materials
High Quality Materials
for High Quality Bioreactor Systems
As a leading supplier of bioreactor systems Applikon takes seriously its commitment to supply
only the highest quality products. In order to achieve this goal it is important to first start with the
procurement of the highest quality materials. The correct selection of material that will be used
for a bioprocess is an important consideration. This document describes the differences between
various types of stainless steel and the effort that Applikon makes in order to ensure that our
bioreactor systems are manufactured only to the utmost standards.
To prevent adverse alteration of the products
frequently 304L, either mechanically polished or elec-
made, pharmaceutical equipment is designed so that
tropolished, are the metal alloy of choice for piping,
product contact surfaces are not reactive, additive, or
tubing, fittings, tanks, and equipment because of
absorptive; so the product is not adversely altered.
these requirements. More recently an even more cor-
Austenitic stainless steel alloys, primarily 316L (due
rosion resistant alloy (AL-6XN) has been used by the
to its better chlorine corrosion resistance) and less
pharmaceutical industry for special applications.
Stainless Steels
Stainless steels are chromium containing steel alloys. The minimum chromium content of the standardized stainless steels is 10.5%. Chromium makes the steel ‘stainless’, this means improved corrosion resistance. The better corrosion resistance is due to a chromium oxide film that is formed on the steel surface. This extremely thin layer, under the right conditions, is also self-repairing.
Different alloying elements
Besides chromium, typical alloying elements are
molybdenum, nickel and nitrogen. Nickel is mostly
alloyed to improve the formability and ductility of
stainless steel. Molybdenum is added to increase
the resistance against chlorine. Alloying these
elements brings out different crystal structures to
enable different properties in machining, forming,
welding etc.
Type 316: chlorine corrosion resistance
By adding 2-3% molybdenum compared to 304,
type 316 stainless steel (SS) has better chloride
corrosion resistance. Type 316 is upgraded by lowering the allowable carbon content to reduce/
eliminate sensitization and slightly increasing the
nickel composition. By containing molybdenum and
increasing the percentages of nickel, this alloy dis-
AL-6XN: most corrosion resistance
AL-6XN was initially intended to be used in a
plays higher strengths at elevated temperatures and
seawater environment, but extensive testing has
better corrosion resistance than the 304 austenitic
demonstrated it to be resistant to a variety of corro-
alloys.
sive elements. Its excellent chloride pitting resistance is attributable to its 6.50% molybdenum con-
Type 316L SS: improved resistance
Type 316L SS is upgraded from normal 316 SS
tent, while its significant resistance to chloride
stress corrosion cracking is a result of its nickel con-
by slightly increasing the percent composition of
tent of about 25.00%. The addition of nitrogen
nickel and lowering the carbon composition. In this
enhances its pitting resistance as well as mechani-
low-carbon austenitic alloy, control of carbon to a
cal strength. Nitrogen also serves to significantly
maximum of 0.03% has been shown to minimize
reduce the formation of potentially harmful second-
carbide precipitation (sensitization) during welding
ary phases during the manufacture of large cross-
and concomitant susceptibility to inter-granular cor-
section products. The AL-6XN alloy was tested
rosion in the Heat Affected Zone (HAZ).
against other stainless steel alloys, and it was
concluded that it is the most corrosion resistant
iron-base austenitic stainless alloy.
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Selecting a Stainless Steel
for Pharmaceutical Applications
There are a large number of stainless steels produced. Corrosion resistance, physical properties, and
mechanical properties are generally among the properties considered when selecting stainless steel
for an application.
For the pharmaceutical industry the
significant characteristic of a stainless steel, but can
most impor tant selection criteria are
also be the most difficult to assess for a specific
• Surface finish
application. General corrosion resistance is com-
• Suitability for intended cleaning procedures
paratively easy to determine, but real environments
• Thermal conductivity
are usually more complex.
• Corrosion resistance
• Resistance to oxidation and sulfidation
Applikon provides all its stainless steel com-
• Resistance to abrasion and erosion
ponents that come in contact with the process
medium with an electropolished surface finish
Corrosion resistance is commonly the most
to a smoothness better than 0.4 µm.
Standard of Country
Chemical composition (weight %)
AISI
W-nr
DIN
C max
SI max
Mn max P max
S max
Ni
Cr
Mo
304
1.4301
X5 Cr Ni18 10
0.08
1.00
2.00
0.045
0.030
8.00 - 10.50
18.00 - 20.00
-
304L
1.4306
X2 CrNi18 10
0.03
1.00
2.00
0.045
0.030
9.00 - 13.00
18.00 - 20.00
-
316
1.4401
X5 Cr Ni Mo 18 10
0.08
1.00
2.00
0.045
0.030
10.00 - 14.00
16.00 - 18.00
2.00 - 3.00
316L
1.4435
X2 Cr NiMo18 10
0.03
1.00
2.00
0.045
0.030
12.00 - 14.00
16.00 - 18.00
2.00 - 3.00
Al-6XN
1.4529
X1 NiCrMoCuN 25 20 6
0.03
1.00
2.00
0.040
0.030
23.50 - 25.50
20.00 - 22.00
6.00 - 7.00
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High Quality Materials
What is Electropolishing?
Electropolishing is the controlled electrochemical
removal of surface metal, resulting in a brilliant
Corrosion resistance
Electropolishing yields maximum tarnish and
corrosion resistance in many metals and alloys.
appearance and improved properties. Sometimes
described as ‘reverse plating’, the process has a
Ease of Cleaning
leveling effect, which produces smoothness and
Electropolishing
increased reflectivity.
• Substantially reduces product contamination
and adhesion due to the microscopic smooth-
How does it work?
Electropolishing is the process of smoothing a
metal surface anodically in a concentrated acid
solution (electrolyte).
The high spots or ‘peaks’ are attacked more
ness of an electropolished surface (much like
a glass surface).
• Decreases cleaning time. Electropolished
surfaces can be effectively hydroblasted in
less time and with less pressure.
rapidly than the low spots or ‘valleys’ to create a
Some companies report that electropolished
smoother, bright surface. At the same time, all impu-
process equipment surfaces have reduced
rities such as scale, rust, foreign debris, oils, grin-
cleaning time by more than 50 percent.
ding compounds and other materials are removed
• Improves sterilization and maintenance of
as the surface material is dissolved.
hygienically clean surfaces.
• Provides best passivation of stainless steel.
The advantage
Unipotentializes stainless steel with the
The ultimate benefits of electropolishing are
oxygen absorbed by the surface, creating
manifest by improved appearance, micro
a monomolecular oxide film.
smoothness, corrosion resistance, cleanability,
and resistance to further contamination and
bacteria growth.
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traceable to the original melt.
Material certification
All stainless steel bioreactor parts manufactu-
There are several documents that can be
supplied to guarantee the quality of stainless
red by Applikon are laser engraved with a unique
steel parts.
production number that is traceable to the production
order at the workshop. This production order con-
Documents that are supplied by the
tains all necessary information regarding steel quali-
manufacturer of the parts are
ty, traceability and the 3.1.B certificate for the mate-
• 2.1 Certificate of compliance (COC), which
rial used in the specific production process. All parts
confirms the delivered material is correspon-
furnished with Applikon stainless steel bioreactors
ding to the agreement without test results.
can be supplied with 3.1B material certificates.
• 2.2 Test report, confirmation based on results
given for products made of the same or
All parts that are potentially exposed to the culture medium are electropolished, resulting in a surface
similar materials.
• 2.3 Specific test reports, confirmation based
on results of tests made on the material itself.
finish having an Ra value of 0.4 micrometer or better
This enhanced surface quality ensures less adhe-
Documents issued by experts
sion of material to the surface and good cleanability.
independent of the manufacturer are
All O-rings and gaskets are manufactured and certi-
• 3.1.A A confirmation issued by an officially
fied using only FDA approved materials.
appointed inspector based on the tests made
• 3.1.B A confirmation issued by the plant
Finally, all Applikon bioreactor systems go
through extensive inspections and test protocols
inspector based on the tests made on the
before the systems are ultimately shipped to our
material itself according to legal rules.
customer.
• 3.1.C A confirmation issued by an expert
nominated by the customer based on the
With the implementation of these procedures
tests made on the material itself according
Applikon assures its customers that they can always
to legal rules.
depend on the fact that the equipment they receive
has been constructed with conscientious and tho-
What does Applikon do?
rough attention to detail. Our customers can rest
All Applikon stainless steel parts for bioreactors
are produced from 3.1B certified materials and
assured knowing that they have selected the right
equipment for their process.
designed to be constructed of AISI 316L stainless
steel. In addition, Applikon performs random checks
In an effort to constantly improve our support we
to make sure that the materials, as supplied, match
welcome your comments and suggestions as to how
the data as documented on the 3.1.B certificates.
we can continue to improve the quality of our pro-
The stock materials that are used are always fully
ducts and services.
Applikon Dependable Instruments bv / Biotechnology Division.
De Brauwweg 13, P.O. Box 149, 3100 AC Schiedam, The Netherlands. Phone: +31 10 298 35 55. Fax: +31 10 437 96 48. E-mail: biotech@applikon.com
www.applikon.com
Applikon Biotechnology - V3XU120011 - Subject to modifications - Printed by Applikon Dependable Instruments bv - The Netherlands August 2004
on the material itself according to legal rules.