THE ULTIMATE LOW EXTRACTABLE SILICONE TUBING
SAINT-GOBAIN PERFORMANCE PLASTICS WHITE PAPER
SANI-TECH® ULTRA.r.1
INTRODUCTION
For several years, pharmaceutical manufacturing professionals
have increasingly stated concerns about material leachables and
extractables and their impact on the products they produce. Fluid
transfer systems that include flexible tubing have been at the
forefront of this discussion. To address these concerns, chemists
and material experts within Saint-Gobain spent the last few years
developing a silicone material that minimizes all potential
contaminants. The product, Sani-Tech® Ultra, has the lowest
extractable level of any commonly used fluid transfer material and
addresses the concerns of the industry with the most comprehensive
body of testing available. Lot traceable, manufactured and packaged
in a ISO Class VII clean room, Sani-Tech® Ultra is the next generation
of silicone materials for pharmaceutical production.
KEY PERFORMANCE ATTRIBUTES:
1. EXTRACTABLES
The main sources of extractables in silicone rubber are low molecular weight siloxane molecules. These siloxane molecules
come from impurities within the raw materials used in the silicone rubber manufacturing process. In theory all of the
extractables can be removed from silicone rubber using a non-polar organic solvent such as hexane at its boiling temperature.
The amount of total extractables in Sani-Tech® Ultra is measured following the procedure defined in European
Pharmacopoeia 3.1.9; this procedure is an extremely aggressive extraction procedure compared to applications where
Sani-Tech® Ultra is used. The results are summarized in Table 1.
Table 1. Extractable contents in Sani-Tech® Ultra silicone tubing
per EP 3.1.9 hexane extraction procedure.
Product
%
Sani-Tech® Ultra50
2.00
Sani-Tech® Ultra65
1.32
Under typical application conditions for Sani-Tech® Ultra, most of the extractables are small siloxane cyclic molecules,
commonly octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6).
The structure of these three molecules is illustrated in Figure 1.
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Figure 1. Molecular structures of low
molecular weight siloxane D4, D5
and D6.
The amount of D4, D5, and D6 in Sani-Tech® Ultra can be measured by extracting them using organic solvents, such as
pentane, and measuring the concentrations of these molecules in the pentane solution. The detailed procedure is described
as follows: the extraction for D4, D5 and D6 from Sani-Tech® Ultra tubing was performed at room temperature for 3 hours
using a mechanical shaker. The concentration of the typical low molecular weight siloxane D4, D5, and D6 in the pentane
extract is analyzed by a GC MS test method. (The test procedure was developed in the 1980’s as a collaborative effect between
the major silicone raw material suppliers and General Motors for the purpose of quantifying silicone volatiles levels in silicone
gasket products, GE C1399.) A known amount of model compound Dodecane was added to the resultant extract as an internal
standard prior to the GC analysis and the typical GC trace is show in Figure 2.
Dodecane
Abundance
18.22
9000000
8000000
7000000
6000000
5000000
4000000
3000000
D5
2000000
Figure 2. GC Chromatogram
of a typical silicone pentane
extraction (Dodecane was
added afterward as internal
reference).
D6
20.04
17.32
D4
14.57
1000000
0
Time
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10.00
12 .00
14.00
16.00
18.00
20.00
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The concentration of Dn was calculated from the area of the relevant Dn peaks in the GC chromatograph. This value is
compared against the area of the internal standard, taking into account the response factor for each Dn which is calculated
from its calibration curves, using known amount of concentration for each data point against the abundance in the chromatogram. The D4, D5, and D6 contents in the pentane extract of Sani-Tech® Ultra 50 and Sani-Tech® Ultra 65 is summarized
in Table 2.
Table 2. Low molecular weight siloxane content in Sani-Tech® Ultra Tubing.
Product
D4 (ppm)
D5 (ppm)
D6 (ppm)
D4 D5 D6 Total (ppm)
Sani-Tech® Ultra50
1
0
1
2
Sani-Tech® Ultra65
24
1
0
25
The majority of silicone tubing used in the biopharm industry is for the transfer of aqueous solutions. As a result, it is important
to know the level and type of extractables inherent in the tubing. A water extractable procedure is set up to measurement
the total organic carbon (TOC) in Sani-Tech® Ultra tubing in this typical cycle and the procedure is described as following:
Two four-foot-long tube samples were autoclaved at 134°C for 60 minutes and then subjected to a deionized (DI) water flush. A
profile of TOC over 20.0 liters of flush volume was obtained to assess the decrease of extractables by means of increasing flush
volumes. Effluent samples were taken throughout the flushing, after 1, 3, 5, 7, 15, and 20 liter flushings. The TOC concentration of
each sample was analyzed using a Phoenix 8000 TOC Analyzer based on persulfate-UV oxidation. The TOC flush profile of
Sani-Tech® Ultra 50 is illustrated in Figure 3.
100
90
Specimen 1
Specimen 2
80
TOC (ppb)
70
60
50
40
30
20
10
0
Figure 3. TOC Flush Profile of
Sani-Tech® Ultra 50 tubing.
1
3
5
7
10
15
20
Flush Volume (L)
The TOC number is taken from the average of the TOC from all the tested samples. The TOC of the WIFI water effluent of
Sani-Tech® Ultra 50 and Sani-Tech® Ultra 65 is summarized in Table 3.
Table 3. WIFI water flush TOC of Sani-Tech® Ultra tubings.
Product
TOC (ppb)
Sani-Tech® Ultra50
8.9
Sani-Tech® Ultra65
10.7
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The amount of extractables of Sani-Tech® Ultra tubing in the typical biopharm application cycles is extremely low, as low as
8.9 parts per billion.
The other water extraction procedure for a silicone tubing product is described in European Pharmacopoeia 3.1.9. The
process is described as follows: 25g of Sani-Tech® Ultra tubings and 500ml of water were placed in a borosilicate glass flask
equipped with a condenser. The mixture was boiled under the reflux condenser for 5 hours. The resulting solution is the
Sani-Tech® tubing water extract.
The low molecular weight siloxane D4, D5, and D6 will leach out into the water solution during this test. Since these materials
are not miscible with water, it causes the solution to become “cloudy” as the result of the extraction. Therefore the degree of
opalescence of the water is correlated to the amount of low molecular weight siloxane extractables. The degree of opalescence in the Sani-Tech® Ultra water extract is determined by instrumental measurement of the light absorbed or scattered
on the account of submicroscopic optical density inhomogeneities of opalescent solutions. The measurement is carried out
on HACH 2100N instrument and according to European Pharmacopoeia 2.2.1 the degree of opalescence in water is defined
as nephelometric turbidity unites (NTU). The results for the selected sizes of Ultra 50 and Ultra 65 are summarized in Tables
4 and 5.
Table 4. Turbidity number of selected size of Sani-Tech® Ultra50 tubings.
Product
ID (inches)
OD (inches)
Wall (inches)
NTU
Ultra-C-312-3F
0.313
0.500
0.094
0.291
Ultra-C-187-3F
0.188
0.375
0.094
0.507
Ultra-C-250-2F
0.250
0.375
0.063
0.29
Ultra-C-375-4F
0.375
0.625
0.125
0.216
Ultra-C-500-4F
0.500
0.750
0.125
0.226
Ultra-C-125-2F
0.125
0.250
0.063
0.241
Table 5. Turbidity number of selected size of Sani-Tech® Ultra65 tubings.
Product
ID (inches)
OD (inches)
Wall (inches)
NTU
Ultra65-CM8-14
0.315
0.551
0.118
0.339
Ultra65-CM13-23H
0.512
0.906
0.197
0.07
Ultra65-C-250-2
0.250
0.375
0.063
0.608
Ultra65-CM5-11
0.197
0.433
0.118
0.457
Ultra65-C-125-2
0.125
0.250
0.063
0.524
Ultra65-CM3-11
0.118
0.433
0.158
0.424
The degree of opalescence in the water extract of Sani-Tech® Ultra tubings are very low as predicted.
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2. DYNAMIC PROPERTIES
The dynamic properties of silicone tubings can also be measured by their performance on peristaltic pumps, in which the
tubing is constantly compressed and stretched to allow transferring of liquid media. The accelerated pump test for Sani-Tech®
Ultra tubing is carried out using a standard procedure recommended by Cole Parmer. Silicone tubes cut to 10 to 12 inch
lengths are loaded into Cole Parmer Masterflex® L/S Standard Pump Heads. Pumps (Cole Parmer Masterflex® L/S VariableSpeed Digital Drive) are turned on and set to run at 600 rpm. Leaks are detected by the Liqui-SenseTM detection system and
the pumps are stopped; the time to failure (pump life) is then calculated and recorded. Eight samples are run for Sani-Tech®
Ultra 50 and the average life is taken. The results are summarized in Table 6 .
Table 6. Peristaltic pump tubing life of Sani-Tech® Ultra tubings.
Product
Sani-Tech® Ultra50
Pump Life (hr)
36
Saint-Gobain Performance Plastics’ silicone tubing is known for its superior pump life, and Sani-Tech® Ultra is no exception
as shown by these test results.
3. STATIC PHYSICAL PROPERTIES
The typical physical properties of Sani-Tech® Ultra are summarized in Table 7.
Table 7. Typical Physical Properties of Sani-Tech® Ultra Compounds.
Property
ASTM Method
Sani-Tech® Ultra 50
Sani-Tech® Ultra 65
D2240
50
65
Tensile strength (psi)
D412
1293
1373
Ultimate Elongation (%)
D412
719
608
Tensile Modulus at 200% elongation (psi)
D412
200
302
Tear Resistance (ppi)
D624
185
179
Specific Gravity
D792
1.14
1.17
Durometer Hardness (Shore A)
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4. BIOCOMPATIBILITY
Both Sani-Tech® Ultra 50 and Sani-Tech® Ultra 65 are compounded by Saint-Gobain Performance Plastics to meet the most
demanding biocompatibility requirements including USP Class VI, ISO10993 and EP3.1.9.
Current industry tests done on Sani-Tech® Ultra:
BIOLOGICAL REACTIVITY
USP <88> Biological Reactivity Tests, In Vivo
USP Class VI Tests
USP Class VI Tests (Post Gamma Sterilization)
USP Class VI Tests (Post Steam Sterilization)
USP <87> Biological Reactivity Tests, In Vitro
Direct Contact
Agar Diffusion Test
MEM Elution
SYSTEMIC TOXICITY
Acute Systemic Injection
Ames Assay
IRRITATION/SENSITIZATION
Kligman Maximization
OTHER
USP <381> Physiochemical Testing for Elastomeric Closures for Injections
USP <661> Physiochemical Testing for Plastics, Containers
Rubber Articles Intended for Repeated Use
Pyrogen
Hemolysis Complete (Direct & Indirect)
European Pharmacopoeia 3.1.9
Japanese Pharmacopoeia- Section 59
Heavy Metal Analysis (Metals Analysis by ICP/MS)
Infrared Analysis and Visible Spectrograph Screen (IR Scan)
USP 788 Particulate Analysis
USP LAL
Gel Clot
Chromogenic
Bacteriostasis Fungistasis- USP 23 <71>
5. AVAILABLE SIZES
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Both Sani-Tech® Ultra 50 and Sani-Tech® Ultra 65 are available in the sizes summarized in Table 8.
Table 8. Sani-Tech® Ultra Tubing Available Sizes
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IMPORTANT: It is the user’s responsibility to ensure the suitability and safety of Saint-Gobain Performance Plastics tubing for all intended uses. Laboratory and clinical tests
must be conducted in accordance with applicable regulatory requirements in order to determine the safety and effectiveness for use of tubing in any particular application.
For a period of 6 months from the date of first sale, Saint-Gobain Performance Plastics Corporation warrants this product to be free from defects in materials and workmanship. Our only obligation will be to replace any portion proving defective, or at our option, to refund the purchase price thereof. User assumes all other risk, if any, including the risk of injury, loss or damage, direct or
consequential, arising out of the use, misuse, or inability to use, this product. THIS WARRANTY IS IN LIEU OF THE WARRANTIES OF MERCHANTABILITY, FITNESS FOR PARTICULAR PURPOSE, AND ALL
OTHER WARRANTIES, EXPRESSED OR IMPLIED. No deviation is authorized.
Saint-Gobain Performance Plastics Corporation assumes no obligations or liability for any advice furnished by it, or for results obtained with respect to those products. All such advice is
given and accepted at the buyer's risk.
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