Technical Information

DuPont Fluoroproducts
Material of Construction for
Pharmaceutical and Biotechnology Processing:
Moving into the 21st Century
James R. Fleming1, David Kemkes1, Richard G. Chatten2,
Lewis E. Creshaw2, and John F. Imbalzano2
1
Entegris, Inc., Chaska, MN
2
DuPont Company, Wilmington, DE

Abstract production cost and lessened downtime for regula-

At the dawn of the new millennium, the Pharmaceu- tory compliance procedures, plus synthesis and
tical and Biotechnology Industries are seeking ways process design freedoms. Proven service in the
to leave behind the currently-used troublesome ma- chemical processing industry for a half century,
terials of construction and to accelerate conversion and in the microelectronics industry for a quarter
to problem-freeing, leading-edge, improved material. century give ready evidence of high purity,
non-wetting and non-corrosive performance, and
Throughout this century, the materials of processing a supply of ample equipment for adoption by the
equipment construction used in these industries— Pharmaceutical and Biotechnology Industries.
stainless steel and glass—imposed constant and Moreover, fluoropolymer fabricators with similar
increasing problems: rouging, pitting, corrosion, years of experience can provide desired specialty
metallic-poisoning, aggravated compliance issues, items. And new fluoropolymer resin offerings from
costly and environmentally adverse cleaning proto- DuPont and other fluoropolymer resin suppliers
cols, and inadvertent fracture, plus costly biofilm further enhance the adaptability of this material to
issues. A cursory assessment suggests that the de- satisfy ongoing Pharmaceutical and Biotechnology
velopment of increasingly sophisticated pharmaceu- Industries’ needs.
tical and biochemical manufacturing product and
processes are being limited by what can be synthe- Many companies are already moving to fluoropoly-
sized and manufactured in glass-lined or, particu- mer material of construction. Not moving quickly is
larly, stainless steel components. likely to negatively impact the remaining companies’
sustained competitive advantage going forward.
Equipment made with wetted surfaces of fluoro-
polymers, especially Teflon® PFA HP, represents
the most functional 21st Century material of con- Introduction, Problem
struction for pharmaceutical and biotechnological Statement, and Objectives
research and manufacturing. The non-polar, high Approaching the turn of the century, the pharmaceu-
service temperature, chemically inert, hydrophobic tical and biotechnology industries confront major
nature of a fluoropolymer surface provides non- challenges: increased competition, industry consoli-
interactive, essentially “force field”-like containment dation and globalization, high research and develop-
for pharmaceutical and biotechnological process ment costs, pervasive government guidelines, and
fluid streams. These attributes promise reduced extremely demanding manufacturing and distribu-
tion requirements.1–7

The DuPont Oval Logo, DuPont™, The miracles of science™,

and Teflon® are trademarks or registered trademarks of
E.I. du Pont de Nemours and Company.
Faced with such issues, these industries rightfully Depending on the amount of the minor ingredients
need to be extremely vigilant in the allocation and in the metallurgical formulation, the chemical resis-
expenditure of resources. Contradictory, however, tance of stainless steel to certain chemicals can be
to the careful planning and execution of resource improved.12 Such improved chemical resistance
expenditures, the pharmaceutical and biotechnology comes with a corresponding increase in cost. But
industries continue to spend untold millions of dol- even such chemical resistance improvement is not
lars to compensate for the shortcomings of materials sufficient to overcome chemical attack13 or the cor-
of construction currently used in the production of rosive attack of biofilm components14. Stainless
their products.a steels corrode over time as the minor ingredients are
lost and as electrochemical potentials arise which
The use of an alternative material of construction8—
promote the oxidation of iron. In stainless steel
namely, fluoropolymers, especially fully fluorinated
weldments, for example, iron is made more readily
fluoropolymers such as Teflon® PFA—affords the
accessible to oxidation in even the “mildest” of
pharmaceutical and biotechnology industries a
chemical conditions15, i.e., hot steam, and the result-
means to redirect these funds to more productive
ing rust (“rouging”) contaminates and compromises
initiatives which impact their business well-being—
the quality of the products being produced in such
research and development or profitability.
equipment.
One objective of this paper is to compare the mate-
Stainless steel can be further chemically treated to
rial science of the current materials of construction
be made less reactive, i.e., passivated16, in a time
–stainless steel and glass—with that of the increas-
consuming and expensive treatment that must be
ingly adopted material of construction—fluoropoly-
performed regularly to ensure that the iron in this
mers. A second objective is to compare biochemical
material doesn’t oxidize—i.e., rust. Passivation is
and microbiological impact on such materials.
costlyb , is only temporarily durable,17 and must be
A third objective is to raise the real potential of re- repeated if additional weldments are incorporated
duced regulatory compliance costs through the use into the system. Passivated or not, stainless steel is
of unreactive unchanging fluoropolymers as mate- reactive to many harsh chemicals18, particularly
rial of construction for pharmaceutical and biotech- chloride and other halides, preventing their bene-
nology processing equipment. And finally, a fourth ficial use in pharmaceutical and biotechnologic
objective is to suggest a redirection, with the aid of applications.
fluoropolymer materials of construction, of the un-
The surface irregularities of stainless steel—ranging
told millions of dollars being spent to compensate
from 180 grit to 400 grit—can be ameliorated, al-
for the shortcomings of stainless steel and glass
though with only temporary beneficial effect, to
materials of construction to other more productive
double digit microinches by electropolishing.19 But,
pharmaceutical and biotechnology industry uses.
electropolishing is also expensive, non-permanent,
and needs to be repeated often to maintain such
Material Science Aspects of a surface.20 Even so, this electro-smoothing only
Stainless Steel, Glass, and miniaturizes the height of the asperities in the metal-
Fluoropolymers lurgical surface, but does little to remove the nooks
and crannies surrounding the base of the asperities
Stainless Steel (Figure 1).
Stainless steel has historically been adopted for con-
Worse still, electropolishing can remove inclusions
tainment of chemical processing because it is resis-
in the metal creating pits, which, in turn, can harbor
tant to more chemicals than is iron or mild steel.9 It
microorganisms and biofilm components to perfectly
is an inorganic chemical combination of essentially
shelter them from even the most vigorous cleaning
iron, chromium, and nickel.10 Products of stainless
(Figure 2).
steel are strong and their initial cost, though higher
than iron or mild steel, are often less than other ex- Surface physical chemistry of stainless steel is
otic metallurgical materials of construction.11 another significant negative for its use in the Phar-
maceutical and Biotechnology industries—it is
a
The cost of corrosion of stainless steel in the Pharmaceutical and wettable by aqueous solutions, a characteristic
Biotechnology Industries in the US in 1998 has been estimated to which enhances not only chemical corrosion,21
be $0.31B, arrived at by taking one tenth of the dollar value obtained but also biofilm adhesion and biofilm resistance
by proportioning these industries’ total 1998 revenue to that of the
US GDP, and multiplying that factor times the % of the GDP estimated to detachment.22
by the US Dept of Commerce for corrosion in the general economy,
i.e., ~ 4%.
b
A conservative estimate of the cost of passivation of a 1000 foot loop
is $10K –$12K, i.e., $10–$12/ft.

2
Figure 1. AFM Photomicrograph Showing Spikes only it didn’t break unexpectedly. If only it could
from Electropolished Asperities endure thermal cycling. If only glass coatings didn’t
Ss 316L 15 Ra
unpredictably craze and thereby expose the under-
lying iron substrate to the process fluids. If only it
didn’t leach elements used to help it overcome its
brittle/crazing shortcomings. If only its surface
wasn’t wetted by aqueous media. If only it didn’t
tenaciously hold onto biofilms. Feedback indicates
that glass surface of most glass-lined vessels in
chemical handling industries ends up as a patchwork
of perfluoropolymer patches held with tantalum
bolts.29 And, of course, glass is reactive to many
harsh chemicals, 30, 31 preventing their beneficial use
in pharmaceutical and biotechnologic applications.

Fluoropolymers
Figure 2. SEM Photomicrograph Showing Pits Because of its outstanding friction reduction,
from Electropolishing Removal of Inclusion material release, chemical resistance, and thermal
Ss 316L 15Ra stability, fluoropolymers, especially Teflon® per-
fluoropolymers, have found increasing applications
as materials of construction in the pharmaceutical
and biotechnology industries.32, 33 ,34 These adoptions
showcase its anti-corrosive and non-wetting surface
characteristics, enhanced by its reduced surface
friction. In combination, these features provide a
comparative advantage vis-a-vis biofilm (see below).
Fully fluorinated fluoropolymers, such as Teflon®
PFA and Teflon® PTFE are electrochemically, bio-
chemically, enzymatically, and chemically virtually
inert. The exceptions chemically are exotic inter-
halogen compounds, molten metals, etchants such
as sodium metal dissolved in napthalene, and im-
pinging gas plasmas.35 Such chemical inertness
Today, the wide availability of components of is not the case for partially fluorinated polymers
Teflon® polymers has made them equivalent in in- which are subject to varying degrees of reactivity
stalled cost to stainless steel components, and they based essentially on their polarity and chemical
provide a lower cost of ownership. structure.36, 37 Figure 3 qualitatively compares the
chemical reactivity differences between fully and
Glass partially fluorinated fluoropolymers.
This centuries-old, amorphous inorganic material Fully fluorinated fluoropolymers can sustain high
of construction is readily formed into components temperature service, up to 260 oC for PFA and
and coatings.23, 24 It is chemically resistant to most PTFE. They can be rapidly thermally cycled below
organic chemicals and many but not all inorganic their service temperatures. Although fully fluori-
chemicals.25 It can be formed into many unsupported nated fluoropolymers do not support combustion,
components and can be further supported by attach- they can be burned as long as the oxidizer and tem-
ment to steel for larger processing components. perature source is present.
By their careful consideration of its shortcomings, Most fully fluorinated fluoropolymers are pure as
the pharmaceutical and biotechnology industries polymerized. Many fluoropolymers, but not all (the
have exploited this material well considering its exception being partially fluorinated polymers), do
positives and negatives26, 27, 28 from a material sci- not require any additives to withstand the harshest
ence perspective. If only glass were not brittle. If of reagents. 38

3
Fully fluorinated fluoropolymer materials of con- Minimized Biofilm Adversity
struction are ductile. They are less mechanically with Teflon® PFA
strong than partially fluorinated polymers. Systems
made from them are widely used. Piping systems Biofilm Removal Significantly
up to 2 inch diameter, operating up to 150 psi are Expedited by Surface of Teflon® PFA
available as piping systems without steel piping Biofilm removal studies conducted by the University
outer support;39 piping systems of diameters larger of Minnesota’s Bioprocess Technical Institute and
than 2’’ and for pressures higher than 150 psi, are reported by Hyde et. al.,42 confirm the ease of re-
available with steel outer support.40 Figure 4 quali- moval of biofilms of E. coli ATCC 8739, Klebsiela
tatively depicts the mechanical comparison between pneumoniae ATCC 12657, and Salmonella
fully and partially fluorinated fluoropolymers. Both choleraisuis biovar typhimurium ATCC 13311
fully and partially fluorinated fluoropolymers can from Teflon® PFA HP. Recasting the data pub-
be abraded by high energy, sharp particle slurries lished by Hyde et. al. (ibid.) shows that 98% to 99%
which are directed perpendicular to the fluoropoly- of area covered by the biofilm on injected molded
mer surface, e.g., sandblasting; otherwise, they are coupons of Teflon® PFA HP was removed by
likely to be unaffected. exposure of the biofilmed coupons to dilute sodium
hypochlorite in a virtually quiescent exposure to the
Fully fluorinated fluoropolymers have the lowest biofilm inactivation protocol with coupons protected
surface energy of all solid materials rendering them from biofilm wash-away fluid flow (Figure 5).
virtually non-wettable by water and by aqueous
solutions. The low surface energy, coupled with The data of Figure 5 show that even surfaces of
chemical inertness and a micro-void-free fully Teflon® PFA HP greatly roughened intentionally by
fluorinated surface makes any kind of adhesion machining, showed 92% removal in this virtually
very difficult to achieve. The resulting benefit to quiescent process. In quantitative terms, the data
the pharmaceutical and biotechnology industries is of Figure 5 show that the biofilm release from the
more uptime and ease of cleaning (see “Minimized conventionally injection-molded surface of Teflon®
Biofilm Advertisty with Teflon® PFA” below). PFA HP exceeded that from the conventionally
molded surface of partially fluorinated fluoropoly-
The initial cost of fluoropolymer protected systems, mer PVDF by 10% to 11%, exceeded that for
heretofore often higher than stainless steel, is now conventionally molded surface of the hydrogenated
comparable, 41 while their lifetime cost-of-ownership polymer polypropylene by 31% to 48%, exceeded
is considerably less—they do not require electro- that from the surface of commercial silicone-treated
polishing, having a highly definitive, hydrophobic, borosilicate glass by 11% to 26%, exceeded that
smooth surface as a natural outcome of their form- from the surface of commercial borosilicate glass
ing technology. They need no “passivation”—ever. by 11% to 100%, and exceeded that from the sur-
Their non-reactivity opens the potential for more face of conventional electropolished 316L stainless
efficient, effective, less-costly cleaning systems steel by 74% to 296%.
which can be more environmentally friendly. This
inertness also promises the potential of fewer regula-
tory compliance issues for manufacturing equipment
since the perfluoropolymer is non-corrosive and
virtually unchangeable under pharmaceutical and
biotechnical conditions.

Figure 4. Comparative Mechanical Properties of

Figure 3. Chemical Resistance of Fluoropolymers Fluoropolymers

HIGHEST PFA, PTFE MORE PVDF

ETFE

FEP

ETFE
MUCH
LOWER PVDF
ENOUGH FEP PFA, PTFE

149 204 260 degrees C. 149 204 260 degrees C.

4
Figure 5. Per Cent Biofilm Removal from Biofilm-Covered Commercial Specimens of 316L Stainless Steel,
Borosilicate Glass, Silicon-Coated Borosilicate Glass, and Teflon® PFA in Essentially Quiescent,
Flow-Protected Exposure to 50 PPM sodium Hypochlorite Solution
Per Cent Biofilm Removal
K. Pneumonia S. Choleraisuis E. coli

Stainless steel 67 25 56
Poly(propylene) 67 75 75
Borosilicate glass 89 0 0
Silicone-coated glass 89 89 78
Poly(vinylidene fluoride) 89 89 89
Teflon® PFA (machined) 92 92 92
Teflon® PFA (injection molded) 99 99 98

Source: Hyde, et. al., ibid.

The ease of biofilm release from the surface of The data of Figure 6 indicate that Teflon® PFA HP
Teflon® PFA HP virtually translates to ease and is more than 156% less wettable than glass, and
speed of cleaning components in pharmaceutical more than 137% less wettable than electropolished
and biotechnology industries which have wetted 316L stainless steel. The depictions of Figure 7
surfaces of Teflon® PFA HP. The economic bene- suggest that water molecules roll on the surface of
fit for such industries are in increased production Teflon® PFA HP much like one would picture solid
“uptime”, and lower manufacturing costs. spheres rolling down a tube (this “rolling” can be
readily experienced by observing a drop of water
Non-Wetting Surface of Teflon® PFA HP “bead up” on a surface of Teflon® PFA HP). The
is Responsible for Superior Biofilm differences in wettability between Teflon® PFA HP,
Release, Wettability of Stainless Steel, glass, and stainless steel reflect the polarity differ-
and Glass Aid Biofilm Retention ences between these materials. Stainless steel and
It is not possible for a substance to chemically ad- glass are very polar materials whereas Teflon® PFA
here to a surface if the substance is unable to wet HP is a non-polar fluoropolymer. This virtual lack
that surface.43 The critical wetting angle of a fluid of polarity in Teflon® PFA HP resists the polar
on a surface is the traditional method adhesion water molecule.
scientists use to establish wettability of a surface This essential lack of wetting by water of the
by a given reagent. The higher the critical angle of surface of Teflon® PFA HP can only result in a
wetting the lower the wettability of that surface to significantly slower initiation of biofilm on the sur-
the wetting fluid.44 face of Teflon® PFA HP. That result, in turn, will
1. Stainless Steel and Glass vs. give rise to increased production “uptime” for the
Teflon® PFA HP pharma- ceutical and biotechnology industries
Hyde et al. determined the water wettability of manufacturing operations.
Teflon® PFA HP fluoropolymer vs 316L stainless
steel and borosilicate glass; these data are tabu-
lated in Figure 6 and are shown schematically in
Figure 7.

Figure 6. Comparison of 18 megaOhm Process Water Wetting Contact Angle for 316L Stainless Steel,
Borosilicate Glass, Teflon® PFA Fluoropolymer Resin
Stainless Steel* Glass* Teflon® PFA*

Degrees 41.5 38.5 98.5

Source: Hyde, et. al., ibid.

*AFM Rms, Nm 41.74 7.42 24.35

5
2. PVDF vs. Teflon® PFA HP Figure 8. Comparison of 18 megaOhm Process
The virtual lack of wetting of Teflon® PFA HP is Water Wetting Contact Angle for
superior not only to that of the inorganic materials Poly(vinylidene fluoride) and Teflon® PFA
Fluoropolymer Resin
of construction such as stainless steel and glass.
The surface of Teflon® PFA HP also is less wettable PVDF Teflon® PFA*
than are the partially fluorinated polymers such
Degrees 71.8 98.5
as poly (vinylidene fluoride), PVDF, as shown in
Figure 8 and schematized in Figure 9. Source: Hyde, et. al., J. Indus. Microb. and Biotech.,
19:142–149, 19997
The data of Figure 8 shows that Teflon® PFA HP is
more than 137% less water-wettable than is PVDF. *AFM Rms, Nm 35.09 24.35
The differences in wettability between PVDF and
Teflon® PFA HP reflect the polarity differences
between these polymers. PVDF is a very polar
fluoropolymer, whereas Teflon® PFA HP is a non- diameter in Teflon® PFA will provide the same
polar fluoropolymer. This lack of polarity resists the volume throughput, other things being equal, as a
polar water molecule. As was pointed out earlier, larger diameter high-frictional-flow stainless steel
the lack of attachment of water to surface of Teflon® piping.45, 46 In addition, existing stainless steel piping
PFA HP suggests a significantly slower initiation of systems can be retrofitted with perfluoropolymer
biofilm on the surface of Teflon® PFA which, in liners to gain all the benefits discussed above
turn, suggests increased production “uptime” for the without sacrificing any volume throughput.
pharmaceutical and biotechnology industries manu-
facturing operations. Conversely, the more wettable Asperity of Surface Teflon® PFA HP is a
PVDF surface would be expected to provide com- Non-Factor in its Biofilm Release but a
paratively less manufacturing operation “uptime”. Significant Factor for Stainless Steel
Work to confirm this aspect in a dynamic system Biofilm Retention
is planned. The data of Figure 5 combined with that of surface
smoothness measurements made of the coupons also
3. Water as Media vs. Nutrient confirm that smoothness of the molded surface of
Solution Teflon® PFA HP, as measured by precision Atomic
The wetting data of Hyde, et.al., ibid, show Force Microscopy, bears little significance to
that when nutrients are added to the water, the biofilm release from this surface (Figure 10).
wettability comparisons are of the same order.
The Ra and Rms data for borosilicate glass and
4. Reduced Flow Friction poly(propylene) are significantly lower than those
The hydrophobic nature of the surface of Teflon® for Teflon® PFA HP, yet the data of Figure 5 show
PFA HP is further complimented by low friction, Teflon® PFA to have significantly greater removal
stick-slip character for fluid flow in piping systems of biofilm. The “Z” data of Figure 8 show that the
having such a wetted surface. The benefit of this conventional electropolished stainless steel is 38 %
combination of properties to the pharmaceutical lower than that for conventionally molded Teflon®
and biotechnical industries is that a smaller pipe PFA, yet the data of Figure 5 shows significantly
more biofilm release for rougher perfluoropolymer
Figure 7. Schematic Representation of Wetting
surface. This same measure data of Figure 8 show
Angles Quantified in Figure 6 the “roughness” of Teflon® PFA HP to be highest
with the other materials being substantially lower.
Wetting Contact Angle Yet the data of Figure 5 confirm the biofilm release
18 megaOHM Process Water from the surface of Teflon® PFA to be significantly
higher than from that of the other materials.
The results of surface asperity and biofilm removal
98.5 from the related data for injected molded vs. ma-
Teflon® PFA chined coupons of Teflon® PFA HP demonstrate
that although the surface of the machined coupon
was 95% to 115% rougher than the injected molded
41.5 38.5
surface, the biofilm release from the machined sur-
face was only 7% poorer than that from the injected
316L Stainless Steel Borosilicate Glass
molded surface.

6
Figure 10. Atomic Force Microscopy Surface Analysis
Nanometers

Ra Rms Z range

Siliconed borosilicate glass 0.84 1.56 35.14

Borosilicate glass 1.11 7.42 78.41
Poly(propylene) 16.19 7.42 78.41
Teflon® PFA (injection molded) 17.17 24.35 438.85
316L Stainless steel 26.64 41.74 293.09
Poly(vinylidene fluoride) 28.48 35.09 244.24
Teflon® PFA (machined) 36.83 47.47 310.99

Source: Hyde, et. al., ibid; Ra - arithmetic average of deviations of traced line from center line along trace; Rms = corresponding
geometric average; Z = largest perpendicular distance measured along the trace line.

The above findings collectively indicate that asperity effectiveness and efficiency.47 For processing sys-
measurements on the surface of conventionally tems in which wetted surfaces are Teflon® PFA HP,
molded Teflon® PFA are non-indicators of biofilm this proactive perspective presages regulatory
adhesion on such a surface. enhancements which improve these industries pro-
ductivity and effectiveness, all of which translate
to more profitable processing.
The Non-corrosive Hydrophobic
Inertness of Teflon® PFA HP
Promises More Latitude in Conclusion
Regulatory Aspects of Pharm- Published data from experiments conducted by the
aceutical and Biotechnology University of Minnesota Bioprocess Technical Insti-
Processing tute confirms that the non-corrosive hydrophobic
A great deal of the current regulatory constraints surface of Teflon® PFA HP releases biofilm virtu-
designed for product consistency and quality appar- ally completely in essentially quiescent non-cleaning
ently result from the corrosive and changing nature protocol biofilm inactivation with 50 ppm sodium
of the current materials of construction. The non- hypochlorite solution. By comparison, the same
corrosive inertness of Teflon® PFA HP removes biofilms were significantly retained by 316L stain-
such concerns, along with associated roughing, less steel, borosilicate glass, siliconed borosilicate
passivation, electropolishing, and glass crazing glass, poly(propylene) or poly(vinylidene fluoride).
and breakage. Precision roughness Atomic Force Microscopy mea-
surements on the substrate coupons confirmed that
The hydrophobic nature of Teflon® PFA portends a the asperity of the surface of Teflon® PFA HP is a
longer time before the inception of biofilm forma- non-factor in biofilm adhesion whereas the asperity
tion, given systems without designed dead volume of other substrate surfaces enhanced biofilm reten-
and with adequate flow velocity. This suggests that tion. The combination of surface roughness and
the time between production stoppage for biofilm biofilm removal data lead intractably to the conclu-
removal can be lengthened. Combined with more sion that, other things being equal, the chemical
speedy and complete removal of biofilm from the polarity of the surface is the key factor enhancing
surface of Teflon® PFA, this lengthening between biofilm retention, and that a non-wetting non-polar
cleanings provides additionally improved production surface of the perfluoropolymer Teflon® PFA HP
uptime. maximizes biofilm release. Studies of biofilm onset
Government regulatory agencies are forward- on, and ease of removal from, the surface of Teflon®
looking in their interest in not impeding improve- PFA HP are planned.
ment in pharmaceutical and biotechnical industries’

7
The non-corrosive non-polar hydrophobic surface of 6. Zoccolante, G., “An Industry View of Pharma-
Teflon® PFA HP promises potential productivity- ceutical Water Regulatory Requirements”,
enhancing easing of regulatory compliance issues INTERPHEX Conference Proceeding,
brought about by materials of construction. pp. 129–134, April 1999.
Using systems in which the wetted surfaces are 7. Richter, I. E., “International Construction:
perfluoropolymer Teflon® PFA HP eliminates the Avoiding and Resolving Disputes”,
cost associated with electropolishing, passivation, INTERPHEX Conference Proceeding,
roughing, protracted cleaning protocols with their pp. 361–368, April 1999.
adverse environmental ramifications, unexpected
8. Leaversuch, R. D., “Fluoropolymers Finding
down-time from cracked glass-lined equipment, and
Growing Use in Drug-making Systems”,
product quality contamination. Processing equip-
Modern Plastics, pp 32–36, March 1998.
ment with wetted surfaces of Teflon® PFA HP prof-
fer significant potential for additional productivity 9. Fontana, M. G., Corrosion Engineering, New
“uptime” with its resulting economic benefit. Instead York: McGraw-Hill, 1986.
of paying for the shortcomings of stainless steel and
10. De Renzo, D. J., Corrosion Resistant Materials
glass materials of construction in pharmaceutical
Handbook, New Jersey: Noyes Data Corpora-
and biotechnology processing equipment, these
tion, 1985.
collective savings, measured in millions of dollars,
would then be available for more productive initia- 11. Eshbach, O. W., Souders, M., Handbook of
tives such as the development of new products or Engineering Fundamentals, New York: John
enhanced profitability. Wiley & Sons, 1975.
The production and product benefits founded by 12. De Renzo, D. J., ibid.
systems manufactured from Teflon® PFA HP are
13. Pruett, K., Compass Corrosion Guide, CA:
available to the pharmaceutical and biotechnology
Compass Publications, 1978.
industries now, to provide enhanced global com-
petitiveness through lower costs and facilitating 14. Geesey, G. G., Gillis, R. J., Zhang, H-J, and
continuing advances in process and product devel- Bremers , P.J., “Influence of Surface Features
opment—strengthening our industry for the 21st on Microbial Colonization and Susceptibility to
century. Corrosion of Stainless Steels Used in the Food
Processing Industry”, in Scholz, D., ed., IIW
Asian Pacific Regional Welding Congress,
Literature Cited 2:693–707, 1996).
1. Maslaton, R., “Creating Manufacturing Excel-
lence Through Cycle-Time Reduction”, 15. Fontana, M. G., ibid.
INTERPHEX Conference Proceeding, 16. Banes, P., “Practicality of Passivation and
pp 243–250, April 1999. Derouging Procedures”, INTERPHEX Confer-
2. Arenciba, J. P., Kramer, C. F., “Management of ence Proceedings, pp 1–10, April, 1999.
Emissions from Pharmaceutical Reactions”, 17. Sixsmith, T. and Jackson, J., “How Piping Ma-
INTERPHEX Conference Proceeding, terials for the Pharmaceutical Industry Compare
pp. 53–60, April 1999. to Each Other”, Ultrapure Water, April, 1999.
3. Seesdorf, D., Simko, D., Fisher, R., “Advanced 18. Kilkeary, J. J., Sowell, T., “New Developments
Fitting Technology Improves Bioprocessing in Pharmaceutical Passivation Technology”,
System Operations”, INTERPHEX Conference INTERPHEX Conference Proceedings,
Proceeding, pp. 23–30, April 1999. pp 39–44, April, 1999.
4. Swinehart, F. M., “Lowering the Cost of 19. Sixsmith, T., and Jackson, J., ibid.
Ownership using Integrated Middleware”,
INTERPHEX Conference Proceeding, 20. Sixsmith, T., and Jackson, J., ibid.
pp. 31–38, April 1999. 21. Fontana, M.G., ibid.
5. Glennon, B., “Control Systems Validation in 22. Pringle, J. H. and Fletcher, M. Applied and
Multipurpose Biopharmaceutical Facilities”, Environmental Microbiology, 45: 811–817,
J. Biotech. 59:53–61, 1997. 1983.

8
23. Reese, R. C., Glass, “Process Industries 38. Shiers, J., ed., Modern Fluoropolymers, Wiley,
Corrosion”, Moniz, B and W. I. Pollock, eds. 1997.
National Association of Corrosion Engineers,
39. Entegris, Inc.,“CYNERGY” System Technical
pp.681–694, 1986.
Guide, 1998.
24. Gackenbach, R. E., “Glass-lined Steel”, Moniz,
40. Crane/Resistoflex, Inc., Design and Layout
B. and W. I. Pollock, eds. National Association
Manual for Corrosion Resistant Plastic Lined
of Corrosion Engineers, pp.695–702, 1986.
Piping Systems, 1999.
25. Pruett, K, ibid.
41. Private Communication, G. Marshall, Entegris,
26. McIntyre, J, A. Harris, D. DeClerck, “Improved Inc. October, 1999.
Glass-lined Reactor Efficiency by Safe,
42. Hyde, F. W., M. Alberg, K. Smith, “Compari-
Effective Cleaning of the Reactor Jacket”,
son of Fluorinated Polymers against Stainless
INTERPHEX Conference Proceedings,
Steel, Glass, and Polypropylene in Microbial
pp 369–376, April, 1999.
Biofilm Adherence and Removal”, J. Ind.
27. Reese, R. C., ibid. Microbiol. & Biotech, 19: 142–149, 1997.
28. Gackenbach, R. E., ibid. 43. Huntsberger, J. R., “The Relationship Between
Wetting and Adhesion”, in Gould, R.F., ed.,
29. Private Communication, Khaladkar, Pradip,
Contact Angle: Wettability and Adhesion,
Engineering Department, DuPont Company,
Advances in Chemistry Series, ACS, 1964.
October, 1999.
44. Zisman, Wm. A., Relation of Equilibrium Con-
30. Fontana, M.G., ibid.
tact Angle to Liquid and Solid Constitution, in
31. Pruett, K, ibid. Gould, R. F., ibid.
32. Leaversuch, R. D., ibid. 45. Heald, C. C., ed., Cameron Hydraulic Data,
18th ed., Ingersoll-Dresser Pumps, Liberty
33. Henley, M., “Equipment Markets”, Ultrapure
Corner, NJ, 1995.
Water, December, 1998, pp 13–15.
46. Avallone, E. R., and T. Baumeister III, eds.,
34. DuPont Magazine, “New Drugs in the Pipe-
Mark’s Standard Handbook for Mechanical
line”, No. 4, 1998.
Engineers, 9th ed., McGraw-Hill, Inc., NY,
35. DuPont Company, Design Handbooks for NY. 1987.
Teflon® PTFE, Teflon® FEP, and Teflon® PFA
47. Wechsler, J., “Streamlining Manufacturing
Fluoropolymer Resins, 1999.
Changes and Compliance”, Pharmaceutical
36. Kerbow, D. L., Ethylene-“Tetrafluoroethylene Technology, May, 1999.
Copolymer Resins”, in Shiers, J., ed., Modern
Fluoropolymers, Wiley, 1997.
37. Seiler, D. A., “PVDF in the Chemical Process
Industry”, in Shiers, J., ibid., 1997.

9
For more information on Fluoroproducts: (302) 479-7731
DuPont Fluoroproducts
P.O. Box 80713
Wilmington, DE 19880-0713
www.teflon.com

Europe Japan Asia Pacific

DuPont de Nemours Int’l SA DuPont Mitsui DuPont China, Limited
DuPont Fluoroproducts Fluorochemicals Co., Ltd. 1122 New World Office Bldg.
2, chemin du Pavillon Chiyoda Honsha Building (East Wing)
P.O. Box 50 5–18, Sarugaku-cho 1-chome 24 Selisbury Road
CH-1218 Le Grand-Saconnex Chiyoda-ku, Tokyo 101 Japan Tsim Sha Tsui
Geneva, Switzerland 81-3-5281-5872 Kowloon
(022) 7175111 Hong Kong
(852) 27341948
[email protected]

Canada South America

DuPont Canada, Inc. DuPont do Brasil S/A
DuPont Fluoroproducts Fluoropolymers
P.O. Box 2200, Streetsville Alameda Itapecuru, 506
7070 Mississauga Road 06454-080 - Alphaville
Mississauga, Ontario, P.O. Box 263
Canada Barueri, Sao Paulo, Brazil
L5M 2H3 0800-171715
(905) 821-5194 [email protected]

The information set forth herein is furnished free of charge and is based on technical data that DuPont believes to be reliable. It is intended for use by persons
having technical skill, at their own discretion and risk. The handling precaution information contained herein is given with the understanding that those using
it will satisfy themselves that their particular conditions of use present no health or safety hazards. Because conditions of product use are outside
our control, we make no warranties, express or implied, and assume no liability in connection with any use of this information. As with any material,
evaluation of any compound under end-use conditions prior to specification is essential. Nothing herein is to be taken as a license to operate
under or a recommendation to infringe any patents.
CAUTION: Do not use in medical applications involving permanent implantation in the human body. For other medical applications, see “DuPont
Medical Caution Statement,” H-50102.

(3/01) RWJ92 Printed in U.S.A.

Reorder No.: H-88813