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FLS-5224VSr2 www.biopharm.saint-gobain.com Page 1 Sani-Tech® STHT®-R Tubing November 1, 2016
Validation Guide Summary
Sani-Tech® STHT®-R Tubing Revision: November 1, 2016
FLS-5224VSr2 www.biopharm.saint-gobain.com Page 2 Sani-Tech® STHT®-R Tubing November 1, 2016
Sani-Tech® STHT®-R Tubing Validation Guide Summary
Table of Contents Page 1. Summary _________________________________________________________________________________________ 3
2. Typical Physical Properties ___________________________________________________________________________ 3
3. Biocompatibility, Physicochemical and Extractable Testing _________________________________________________ 4
a. Materials of Construction ____________________________________________________________________ 4
b. Summary __________________________________________________________________________________ 4
c. Kinetic Limulus Amebocyte Lysate Endotoxin _____________________________________________________ 5
d. Limulus Amebocyte Lysate Endotoxin ___________________________________________________________ 5
e. Biological Reactivity Tests, In Vitro – MEM Elution _________________________________________________ 6
f. Biological Reactivity Tests, In Vitro – MEM Elution – Post-Gamma Irradiation ___________________________ 6
g. Biological Reactivity Tests, In Vitro – Agar Diffusion ________________________________________________ 7
h. Biological Reactivity Tests, In Vivo: Pre-Autoclave/Gamma Irradiation Samples _________________________ 7
i. Elastomeric Closures for Injection ______________________________________________________________ 8
j. Total Organic Carbon Analysis – Control, 0 Autoclave Cycles_________________________________________ 8
k. Total Organic Carbon Analysis – Control, 1 Autoclave Cycle _________________________________________ 9
l. Total Organic Carbon Analysis – 5 Autoclave Cycles ________________________________________________ 9
m. Total Organic Carbon Analysis – 10 Autoclave Cycles ______________________________________________ 10
n. Physicochemical Tests for Plastics _____________________________________________________________ 10
o. Particulate Matter _________________________________________________________________________ 11
p. Total Extractables in Rubber Articles Intended for Repeated Use ____________________________________ 12
q. Semi-Quantification and Identification of Extractables: Post-Autoclave _______________________________ 12
r. Semi-Quantification and Identification of Extractables: Post-Gamma Irradiation _______________________ 16
4. Revisions to FLS-5224VS Sani-Tech® STHT®-R Validation Summary ______________________________________ 21
a. Revisions 3.23.16: (.r1) ______________________________________________________________________ 21
b. Revisions 10.31.16: (.r2) _____________________________________________________________________ 21
Saint-Gobain Performance Plastics Terms of Use & Confidentiality Statement
PLEASE NOTE: In receiving this Validation Summary you have agreed to possess ONLY ONE COPY of this validation information. You are also agreeing to NOT
forward disseminate, either electronically or in print, totally or in part, any of the information contained in this material without the express written consent of
Saint-Gobain Performance Plastics Corporation. If you have any questions about these terms please contact: [email protected].
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Validation Guide Summary: Sani-Tech® STHT®-R Braid Reinforced Silicone Tubing 1.0 Summary
Sani-Tech® STHT®-R platinum-cured braid-reinforced silicone tubing is an ultra-flexible, high-purity tubing that was developed
for higher-pressure applications Sani-Tech® STHT®-R tubing is manufactured with Sani-Tech® 65 brand silicone resin.
Sani-Tech® STHT®-R tubing is temperature stable from -80°F (-62°C) to 500°F (260°C). Sani-Tech STHT®-R has an improved
bend radius over wire-reinforced silicone hose. It is sterilizable via autoclave, gamma irradiation and ethylene oxide. Sani-
Tech® STHT®-R tubing is available in custom colors.
Sani-Tech® STHT®-R meets all relevant USP Class VI requirements. Sani-Tech® STHT®-R tubing is manufactured and packaged
in a certified clean room.
Saint-Gobain Validation Guide Summaries are intended to provide users of Sani-Tech® STHT®-R with the technical information
necessary to perform a product pre-implementation risk assessment and to determine the suitability of this product for use in
the intended application. Validation Guide Summaries are not a substitute or a supplement for Quality Control Specifications
or Certifications.
2.0 Typical Physical Properties
Property ASTM Standard
Durometer Hardness, Shore A, 15 Sec. D2240 65
Tensile Strength, psi/MPa D412 1376/8.62
Ultimate Elongation, % D412 668
Tear Resistance, ppi / kN / m D624 326/43.8
Specific Gravity D792 1.17
Tensile Modulus D412 444
Unless otherwise noted, all tests were conducted at room temperature (73*F). Values shown were determined on 0.075” thick
extruded strip or 0.075 thick molded ASTM Durometer buttons.
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3.0 Sani-Tech® STHT®-R Biocompatibility, Physiochemical & Extractable Testing
3a. Materials of Construction The STHT®-R tubing product is constructed of two layers of Sani-Tech® 65 silicone with polyester fiber in-between the
two silicone layers.
3b. Summary The following is a summary of the validation testing that has been performed on Sani-Tech® STHT®-R tubing.
Complete testing reports can be found in the Sani-Tech® STHT®-R Validation Guide.
Test Standard Result
Kinetic LAL Endotoxin USP <85> 0.00538 EU/ml
LAL Gel Clot Endotoxin – Post Steam Sterilization USP <87> Passed
Biological Reactivity Tests, In Vitro: MEM Elution USP <87> Passed
Biological Reactivity Tests, In Vitro: MEM Elution – Post-Gamma Irradiation
USP <87> Passed
Biological Reactivity Tests, In Vitro: Agar Diffusion USP <87> Passed
Biological Reactivity Tests, In Vivo: Pre-Autoclave/Gamma Irradiation USP <88> Passed
Elastomeric Closures for Injection, See Summary, Section 3i. USP <381>
Total Organic Carbon – Control, 0 Autoclave Cycles USP <643> 24.5 mg/l
Total Organic Carbon – Control, 1 Autoclave Cycle USP <643> 7.59 mg/l
Total Organic Carbon -- 5 Autoclave Cycles USP <643> 4.19 mg/l
Total Organic Carbon - 10 Autoclave Cycles USP <643> 3.77 mg/l
Physicochemical Tests for Plastics USP <661> Passed
Particulate Matter, See Summary, Section 3o. USP 788>
Total Extractables in Rubber Articles Intended for Repeated Use 21 CFR Part 117.2600 Passed
Semi-Quantification and Identification of Extractables: Post-Autoclave
See Summary, Section 3q.
Semi-Quantification and Identification of Extractables: Post-Autoclave
See Summary, Section 3r.
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3c. USP <85> Kinetic Limulus Amebocyte Lysate Endotoxin Test
Endotoxins are lipopolysaccharide complexes found in Gram negative bacterial cell walls. They can cause significant
illness in humans. The Limulus Amebocyte Lysate (LAL) Gel Clot Test is used to detect and quantify endotoxin levels in
test samples.
Test: Samples of Sani-Tech® STHT®-R were tested by Toxikon Corporation in accordance with USP 31, NF 26, 2008; <85>
Bacterial Endotoxins Test; Guidelines of Validation of the Limulus Amebocyte Lysate Test as an End-Product Endotoxin
Test for Human and Animal Parenteral Drugs, Biological products and Medical Devices, December 1987.
The fluid pathway of the test article was immersed in 40ml of Sterile Water for Injection for 60 minutes at room
temperature. The extracts were tested in duplicate at the neat concentration. A positive product control (PPC) was
prepared by adding a 0.1ml of the 5.0 EU/ml endotoxin standard to 0.9ml of test article. LAL Reagent water (endotoxin-
free) was used as negative controls. Test article samples, PPC samples, and negative control samples were added to a
microtiter plate and incubated at 37oC for 10 minutes. After incubation 0.1ml of LAL was added to each well and the plate
was placed in a plate reader. The absorbance was measured at 405 nm.
Results: The results are summarized in the table below.
Dilution Raw EU/ml Corrected EU/ml Valid PPC?
Neat 0.00538 0.00538 Yes
3d. USP <85> Limulus Amebocyte Lysate Endotoxin Test
Endotoxins are lipopolysaccharide complexes found in Gram negative bacterial cell walls. They can cause significant
illness in humans. The Limulus Amebocyte Lysate (LAL) Gel Clot Test is used to detect and quantify endotoxin levels in
test samples.
Test: Samples of Sani-Tech® STHT®-R were tested by Toxikon Corporation in accordance with USP 31, NF 26, 2008, <85>
Bacterial Endotoxins Test; Guidelines of Validation of the Limulus Amebocyte Lysate Test as an End-Product Endotoxin
Test for Human and Animal Parenteral Drugs, Biological products and Medical Devices, December 1987.
The fluid pathway of the test article was filled with 40ml of Sterile Water for Injection (SWFI), and held for 60 minutes at
room temperature. The extracts were tested in duplicate at the neat concentration. A positive control was prepared in
duplicate using serial dilutions of endotoxin standard. A positive product control was prepared using the test article
extract and the endotoxin standard. Sterile WFI and LAL Reagent water (endotoxin-free) were used as negative controls.
LAL was added to all test and control samples, which were then incubated at 37oC for 60 minutes.
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Results: Both the positive control and positive product controls demonstrated agglutination indicating that the product
did not interfere with the test. Neither the negative control samples nor the product test samples showed agglutination.
The endotoxin level was therefore determined to be below the limit of detection for this assay, i.e. <0.06 EU/ml. The test
articles were certified endotoxin-free.
3e. USP <87> Biological Reactivity Tests, In Vitro - MEM Elution Test
Cytotoxicity testing assesses the potential of a given material to have a toxic effect on living cells.
Test: Samples of Sani-Tech® STHT®-R were tested by Toxikon Corporation in accordance with USP 31, NF 26, 2008; <87>
Biological Reactivity Tests, In Vitro.
Test samples were immersed in Serum-Supplemented Minimum Essential Medium at 37oC for 24hrs at a ratio of 60
cm2/20 ml. Positive control (Natural Rubber) and negative control (Negative Control Plastic) samples were also extracted
as above. Duplicates of all three extracts were incubated with L929 mouse fibroblast cells at 37oC for 48hrs. Cultures
were monitored for cellular degeneration and malformation and rated on a scale of 0 (No Biological Reactivity) to 4
(Severe Biological Reactivity).
Results: The test article samples and the negative controls scored a Grade 0 for Biological Reactivity after 48hrs. The
positive controls scored a Grade 4 at the 48hr mark. Samples are deemed to meet the test requirements if they exhibit a
Biological Reactivity of no more than Grade 2 (Mild Reactivity). The test articles are therefore considered non-cytotoxic.
3f. USP <87> Biological Reactivity Tests, In Vitro - MEM Elution Test: Post-Gamma Irradiation
Cytotoxicity testing assesses the potential of a given material to have a toxic effect on living cells.
Test: Samples of Sani-Tech® STHT®-R that had been gamma irradiated were tested by NAMSA in accordance with USP 37,
NF 32, 2014; <87> Biological Reactivity Tests, In Vitro.
Test samples were immersed in Serum-Supplemented Minimum Essential Medium at 37oC for 24hrs. Positive control
(USP Reference Standard – Positive BioReaction) and negative control (HDPE) samples were also extracted as above.
Duplicates of all three extracts were incubated with L929 mouse fibroblast cells at 37oC for 48hrs. Cultures were
monitored for cellular degeneration and malformation and rated on a scale of 0 (No Biological Reactivity) to 4 (Severe
Biological Reactivity).
Results: The test article samples and the negative controls scored a Grade 0 for Biological Reactivity after 48hrs. The
positive controls scored a Grade 4 at the 48hr mark. Samples are deemed to meet the test requirements if they exhibit a
Biological Reactivity of no more than Grade 2 (Mild Reactivity). The test articles are therefore considered non-cytotoxic.
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3g. USP <87> Biological Reactivity Tests, In Vitro – Agar Diffusion Test
Cytotoxicity testing assesses the potential of a given material to have a toxic effect on living cells.
Test: Samples of Sani-Tech® STHT®-R were tested by Toxikon Corporation in accordance with USP 31, NF 26, 2008; <87>
Biological Reactivity Tests, In Vitro.
Test article, negative control (Negative Control Plastic) and positive control (Buna-N-Rubber) samples were placed in
separate wells containing solidified agarose stained with vital dye (neutral red) overlaying an L929 mouse fibroblast
monolayer. The culture plates were then incubated at 37oC in 5% CO2 for 24hrs. After the incubation period cultures were
examined macroscopically and microscopically for cell decolorization and potential cell lysis and rated on a scale of 0 (No
Biological Reactivity) to 4 (Severe Biological Reactivity).
Results: The test article samples and the negative controls scored a Grade 0 for Biological Reactivity after 48hrs. The
positive controls scored a Grade 3 at the 48hr mark. Samples are deemed to meet the test requirements if they exhibit a
Biological Reactivity of no more than Grade 2 (Mild Reactivity). The test articles are therefore considered non-cytotoxic.
3h. USP <88> Biological Reactivity Tests, In Vivo: Pre-Autoclave/Gamma Irradiation Samples
The USP Class VI Plastics Test assesses the potential toxicity of a given test article by introducing a sample into live
animals systemically, intracutaneously and through implantation. Test animals are then monitored for signs of irritation
and/or toxicity.
Test: Samples of Sani-Tech® STHT®-R were tested by Toxikon Corporation in accordance with USP 31, NF 26, 2008, <88>
Biological Reactivity Tests, In Vivo.
Test articles were immersed in USP 0.9% Sodium Chloride (NaCl), Cottonseed Oil (CSO), 1 in 20 Ethanol in NaCl (EtOH) or
Polyethylene Glycol 400 (PEG) at 70oC for 24hrs. The test article extracts and corresponding controls (samples of each
extractant that had not been exposed to the test article) were injected systemically into mice and intracutaneously into
rabbits and the animals were observed for 72hrs for signs of skin reactivity or toxicity. In addition, the test article was
implanted into the paravertebral muscles of rabbits, which were then observed for 7 days for macroscopic signs of
hemorrhage, necrosis, discoloration, encapsulation and/or infection.
Results: None of the animals injected systemically with test article extracts or controls exhibited any signs of toxicity.
Similarly, none of the animals injected intracutaneously with test article extracts or controls exhibited any signs of
erythema, edema or clinical toxicity. Further, none of the implanted animals exhibited any signs of toxicity at the
implantation sites relative to the control sites. The test article therefore met the requirements of the USP Class VI Test for
Biocompatibility.
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3i. USP <381> Elastomeric Closures for Injection
Testing of elastomeric closures for use with containers for injectables is performed to assess the suitability of the test
article for use in contact with drug products for parenteral administration in humans.
Test: A sample of Sani-Tech® STHT®-R was tested by Toxikon Corporation in accordance with USP 31, NF 26, 2008; <381>
Elastomeric Closures for Injections.
The test article extracts were prepared by immersing duplicate test article samples (106.8 cm2) in purified water and
autoclaving at 121oC for 30 minutes, then rinsing twice with purified water. One of the duplicate test articles was
subsequently immersed in 212 ml of fresh purified water and autoclaved at 121oC for 2hrs. The other test article sample
was extracted in 212 ml of Isopropyl Alcohol (IPA) by reflux apparatus for 30 minutes. The test extracts were then tested
for Turbidity, Reducing Agents, Heavy Metals, pH Change and Total Extractables per USP <381>.
Results: The test results are summarized in the table below.
Parameter Results
Water IPA
Turbidity 0.2 NTU 0.0 NTU
Total Extractables 0 mg 43 mg
Reducing Agents 0.35 ml Not applicable
Heavy Metals ≤ 1.0 ppm Not applicable
pH Change 0.23 Not applicable
3j. USP <643> Total Organic Carbon Analysis – Control, 0 Autoclave Cycles
The test for Total Organic Carbon provides an indirect measure of the total organic matter present in a given sample.
Test: A sample of Sani-Tech® STHT®-R was tested by Toxikon Corporation in accordance with USP 31, NF 26, 2008; <643>
Total Organic Carbon.
An 80 cm sample of the test article was immersed in 37 ml of Purified Water at 70oC for 24hrs. The Total Organic Carbon
in the test article extract was determined by converting TOC to carbon dioxide through acidification and chemical wet
oxidation with sodium persulfate. The CO2 released by the extract was measured using an infrared detector.
Results: The results of the test are summarized in the table below.
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Sample Results Detection Limit
(mg/l) (mg/l) (mg/cm)
Sani-Tech® STHT®-R 24.5 0.011 0.1
3k. USP <643> Total Organic Carbon Analysis – Control, 1 Autoclave Cycle
The test for Total Organic Carbon provides an indirect measure of the total organic matter present in a given sample.
Test: A sample of Sani-Tech® STHT®-R was tested by Toxikon Corporation in accordance with USP 31, NF 26, 2008; <643>
Total Organic Carbon.
An 80 cm test article sample was autoclaved at 134oC for 30 minutes. The test article was then immersed in 37 ml of
Purified Water at 70oC for 24hrs. The Total Organic Carbon in the test article extract was determined by converting TOC
to carbon dioxide through acidification and chemical wet oxidation with sodium persulfate. The CO2 released by the
extract was measured using an infrared detector.
Results: The results of the test are summarized in the table below.
Sample Results Detection Limit
(mg/l) (mg/l) (mg/cm)
Sani-Tech® STHT®-R 7.59 0.004 0.1
3l. USP <643> Total Organic Carbon Analysis – 5 Autoclave Cycles
The test for Total Organic Carbon provides an indirect measure of the total organic matter present in a given sample.
Test: A sample of Sani-Tech® STHT®-R was tested by Toxikon Corporation in accordance with USP 31, NF 26, 2008; <643>
Total Organic Carbon.
A 75 cm test article sample was autoclaved for 5 cycles at 134oC for 30 minutes. The test article was then immersed in 35
ml of Purified Water at 70oC for 24hrs. The Total Organic Carbon in the test article extract was determined by converting
TOC to carbon dioxide through acidification and chemical wet oxidation with sodium persulfate. The CO2 released by the
extract was measured using an infrared detector.
Results: The results of the test are summarized in the table below.
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Sample Results Detection Limit
(mg/l) (mg/l) (mg/cm)
Sani-Tech® STHT®-R 4.19 0.002 0.1
3m. USP <643> Total Organic Carbon Analysis – 10 Autoclave Cycles
The test for Total Organic Carbon provides an indirect measure of the total organic matter present in a given sample.
Test: A sample of Sani-Tech® STHT®-R was tested by Toxikon Corporation in accordance with USP 31, NF 26, 2008; <643>
Total Organic Carbon.
An 80 cm test article sample was autoclaved for 10 cycles at 134oC for 30 minutes. The test article was then immersed in
Purified Water at 70oC for 24hrs. The Total Organic Carbon in the test article extract was determined by converting TOC
to carbon dioxide through acidification and chemical wet oxidation with sodium persulfate. The CO2 released by the
extract was measured using an infrared detector.
Results: The results of the test are summarized in the table below.
Sample Results Detection Limit
(mg/l) (mg/l) (mg/cm)
Sani-Tech® STHT®-R 3.77 0.002 0.1
3n. USP <661> Physicochemical Tests for Plastics
Physicochemical testing is performed to assess the suitability of the test article for use in contact with drug products for
parenteral administration in humans.
Test: A sample of Sani-Tech® STHT®-R was tested by Toxikon Corporation in accordance with USP 31, NF 26, 2008; <661>
Containers, Physicochemical Tests – Plastics.
The test article was immersed in USP Purified Water for 70oC for 24hrs at a ratio of 120 cm
2/20 ml. The extract was then
tested for Non-Volatile Residue, Residue on Ignition, Heavy Metals as Lead and Buffering Capacity per USP <661>.
Results: The test results are summarized in the table below.
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Assay Assay Results Limits Based on Area
Non-Volatile Residue 0.0 mg ≤ 15 mg
Residue on Ignition Not applicable ≤ 5 mg
Heavy Metals Meets Criteria ≤ 1 ppm
Buffering Capacity 0.0 ml ≤ 10 ml
The test article sample met the criteria established per USP <661> for all of the tests performed, as shown above.
3o. USP <788> Particulate Matter
Solutions intended for parenteral use must meet specified limits for microscopic particles and fibers. The limits are based
on the dosage of the given injectable solution and the test must therefore be performed on the final drug product as part
of product release testing. The test is also typically performed on tubing, connectors and other products which will come
in contact with injectable solutions, for the information of prospective users.
Test: Three 1 foot samples of post gamma irradiated (25 – 40 kGy) STHT®-R were tested by NAMSA in accordance with
USP 36, NF 31, 2013; <788> Particulate Matter in Injections.
The fluid pathway of the test articles were flushed with 50 ml of particle free water. The rinsate was then vacuum
filtered. Control samples were prepared in a similar manner to determine background counts. The filters were dried and
then the particles on each filter membrane were counted using a microscope. The results were normalized using a worst
case 10x internal tube volume flush based on fluid transfer or sampling applications.
Results: The results are summarized in the table below.
Sample Lot Corrected Results (particles/ml)
≥ 10 m ≥ 25 m
STHT®-R (1/2”x5/8”)
1 0.019 0.013
2 0.006 0.003
3 0.005 0.003
Average Test Article Particle Count 0.010 0.006
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3p. 21 CFR Part 117.2600 Total Extractables in Rubber Articles Intended for Repeated Use
The Total Extractables Test is intended to determine the total solids per unit surface area that can be extracted from a
given test article using purified water and hexane.
Test: A sample of Sani-Tech® STHT®-R was tested by Toxikon Corporation in accordance with 21 CFR Part 177.2600:
Rubber Articles Intended for Repeated Use.
The test articles were immersed in either purified water or hexane for 7hrs (the Reflux Time) at a ratio of 7.46 in2/150 ml.
The test articles were then removed and extracted with fresh samples of purified water and n-hexane for a further 2hrs.
The resulting extracts were then evaporated to dryness and the residue per unit surface area was determined for each
sample.
Results: The test results are summarized in the table below.
Reflux Time Purified Water
Results Evaluation Criteria Meets Criteria?
First 7 Hours 0 mg/in2 ≤ 20 mg/in
2 Yes
Second 2 Hours 0 mg/in2 ≤ 1 mg/in
2 Yes
Reflux Time n-Hexane
Results Evaluation Criteria Meets Criteria?
First 7 Hours 41.0 mg/in2 ≤ 175 mg/in
2 Yes
Second 2 Hours 3.12 mg/in2 ≤ 4 mg/in
2 Yes
As shown in the table above, the test article samples met the criteria established per 21 CFR Part 177.2600: Rubber
Articles Intended for Repeated Use.
3q. Semi-Quantification and Identification of Extractables: Post-Autoclave Extractable testing is performed to determine the chemical compounds that will migrate from a given material under
aggressive yet relevant extraction conditions. The results of extractable testing can be used to guide the design of an
appropriate leachable study.
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Test: Samples of Sani-Tech® STHT®-R that had been autoclaved were analyzed by Toxikon Corporation in accordance
with ISO 10993-18, Biological Evaluation of Medical Devices – Part 18: Chemical Characterization of Materials; ASTM
D4128-06 Standard Guide for Identification and Quantitation of Organic Compounds in Water by Combined Gas
Chromatography and Electron Impact Mass Spectrometry; SW 846 Method 5030B, 1996, US EPA, Purge and Trap for
Aqueous Samples; SW 846 Method 3510C, 1996, US EPA, Separatory Funnel Liquid-Liquid Extraction; SW 846 Method
6010B, 1996, US EPA Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP); USP 36, NF 31, 2013 <621>
Chromatography; USP 36, NF 31, 2013 <730> Plasma Spectrochemistry; USP 36, NF 31, 2013 <736> Gas
Chromatography/Mass Spectrometry and Liquid Chromatography/Mass Spectrometry. The test article extracts were
analyzed to identify and semi-quantify any extractable compounds present, using the following analytical techniques:
Gravimetric analysis for non-volatile residue (NVR)
Total organic carbon (TOC) for Purified Water extract only
Inductively coupled plasma (ICP-MS) for analysis of trace metals
Gas chromatography/mass spectrometry (GC/MS) for volatile organic compounds (VOC) and semi-volatile organic
compounds (SVOC)
Liquid chromatography/mass spectrometry (LC/MS) for non-volatile organic compounds (NVOC) and organic acids
Liquid chromatography with UV scan (LC-UV) for non-target non-volatile organic compounds (non-target NVOC)
All analytic methods employed in this study have a minimum detection limit of 1 µg/ml for the chemical compounds that
are known to be potential extractables.
Test article samples were extracted in either Purified Water or 70% Ethanol with agitation at 70oC for 24 hrs. Samples
were extracted by immersion at a ratio of 6 cm2/ml.
Results: The results are summarized in the tables below.
Table 1: NVR and TOC Results
Solvent NVR (mg)
TOC (mg)
Purified Water 0.4 9.77
70% Ethanol 0 N/A
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Table 2: Metals Analysis by ICP-MS
Element Purified Water
(g/l)
70% Ethanol
(g/l)
Aluminum ND* ND*
Antimony ND* ND*
Arsenic ND* ND*
Barium ND* 3.34
Beryllium ND* ND*
Boron 81.7 1395
Cadmium ND* ND*
Calcium ND* 212
Chromium ND* 1.44
Cobalt ND* ND*
Copper ND* 5.85
Iridium ND* ND*
Iron ND* ND*
Lead ND* ND*
Magnesium ND* 13.2
Manganese ND* ND*
Mercury ND* ND*
Molybdenum 2.14 4.16
Nickel 2.66 2.56
Palladium ND* ND*
Platinum 11.0 172
Potassium ND* 715
Rhodium ND* ND*
Ruthenium ND* ND*
Selenium ND* ND*
Silver ND* ND*
Sodium 195 13103
Thallium ND* ND*
Titanium ND* ND*
Tungsten ND* ND*
Vanadium ND* 1.46
Zinc 6.13 46.0
* ND = Not Detected at Reporting Limit
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Table 3: Headspace GC-MS Analysis of Volatile Organic Compounds (VOC)
Solvent Compounds Detected Retention Time
(min)
Results
(g/l) CAS #
Purified Water Isopropyl alcohol 2.43 148 67-63-0
Trimethylsilanol 4.66 242 1066-40-6
70% Ethanol None
Table 4: GC-MS Analysis of Semi-Volatile Organic Compounds (SVOC)
Solvent Compounds Detected Retention Time (min)
Results
(g/l) CAS #
Purified Water 4-Hydroxy-4-methyl-2-pentanone 8.02 37.3 123-42-2
Dodecamethylcyclohexasiloxane 17.5 2.31 540-97-8
70% Ethanol
Diethoxydimethylsilane 5.91 36.9 78-62-6
1,3-Diethoxy-1,1,3,3-tetramethyldisiloxane
10.5 8.49 18420-09-2
Siloxane 14.1 2.70 N/A
Decamethylcyclopentasiloxane 14.4 4.35 541-02-6
Unknown 20.0 3.59 N/A
Cyclohexasiloxane 22.4 7.12 540-97-6
Unknown 24.5 8.00 N/A
Unknown 26.1 6.75 N/A
Unknown 27.5 4.14 N/A
Unknown 28.7 2.08 N/A
Table 5: LC-MS Analysis of Non-Volatile Organic Compounds (NVOC)
Solvent Compounds Detected Retention Time (min)
Results
(g/l) CAS #
Purified Water None
70% Ethanol Myristic Acid 5.21 0.231 544-63-8
Erucamide 7.90 0.288 112-84-5
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Table 6: LC-UV Analysis of Non-Volatile Organic Compounds (NVOC)
Solvent Additional Peaks Retention Time (min)
Wavelength (nm)
Purified Water None
70% Ethanol Yes 4.17 223
3r. Semi-Quantification and Identification of Extractables: Post-Gamma Irradiation Extractable testing is performed to determine the chemical compounds that will migrate from a given material under
aggressive yet relevant extraction conditions. The results of extractable testing can be used to guide the design of an
appropriate leachable study.
Test: Samples of Sani-Tech® STHT®-R that had been gamma irradiated were analyzed by Toxikon Corporation in
accordance with ISO 10993-18, Biological Evaluation of Medical Devices – Part 18: Chemical Characterization of Materials;
ASTM D4128-06 Standard Guide for Identification and Quantitation of Organic Compounds in Water by Combined Gas
Chromatography and Electron Impact Mass Spectrometry; SW 846 Method 5030B, 1996, US EPA, Purge and Trap for
Aqueous Samples; SW 846 Method 3510C, 1996, US EPA, Separatory Funnel Liquid-Liquid Extraction; SW 846 Method
6010B, 1996, US EPA Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP); USP 36, NF 31, 2013 <621>
Chromatography; USP 36, NF 31, 2013 <730> Plasma Spectrochemistry; USP 36, NF 31, 2013 <736> Gas
Chromatography/Mass Spectrometry and Liquid Chromatography/Mass Spectrometry. The test article extracts were
analyzed to identify and semi-quantify any extractable compounds present, using the following analytical techniques:
Gravimetric analysis for non-volatile residue (NVR)
Total organic carbon (TOC) for Purified Water extract only
Inductively coupled plasma (ICP-MS) for analysis of trace metals
Gas chromatography/mass spectrometry (GC/MS) for volatile organic compounds (VOC) and semi-volatile organic
compounds (SVOC)
Liquid chromatography/mass spectrometry (LC/MS) for non-volatile organic compounds (NVOC) and organic acids
Liquid chromatography with UV scan (LC-UV) for non-target non-volatile organic compounds (non-target NVOC)
All analytic methods employed in this study have a minimum detection limit of 1 µg/ml for the chemical compounds that
are known to be potential extractables.
Test article samples were extracted in either Purified Water or 70% Ethanol with agitation at 70oC for 24 hrs. Samples
were extracted by immersion at a ratio of 6 cm2/ml.
Results: The results are summarized in the tables below.
FLS-5224VSr2 www.biopharm.saint-gobain.com Page 17 Sani-Tech® STHT®-R Tubing November 1, 2016
Table 1: NVR and TOC Results
Solvent NVR (mg)
TOC (mg)
Purified Water 0.0 19.9
70% Ethanol 5.6 N/A
Table 2: Metals Analysis by ICP-MS
Element Purified Water
(g/l)
70% Ethanol
(g/l)
Aluminum 162 145
Antimony ND* ND*
Arsenic ND* ND*
Barium 6.56 ND*
Beryllium ND* ND*
Boron 1640 2313
Cadmium ND* ND*
Calcium 1398 4013
Chromium 6.56 2.25
Cobalt 5.92 2.17
Copper 1.14 30.1
Iridium ND* ND*
Iron 89.0 25.4
Lead 1.13 ND*
Magnesium 295 252
Manganese 3.05 ND*
Mercury ND* ND*
Molybdenum ND* 2.51
Nickel 11.6 5.96
Osmium ND* ND*
Palladium ND* ND*
FLS-5224VSr2 www.biopharm.saint-gobain.com Page 18 Sani-Tech® STHT®-R Tubing November 1, 2016
Platinum 96.1 11.5
Potassium 353 296
Rhodium ND* ND*
Ruthenium ND* ND*
Selenium ND* ND*
Silver ND* ND*
Sodium 12469 ND*
Thallium ND* ND*
Titanium ND* ND*
Tungsten ND* ND*
Vanadium ND* 1.20
Zinc 7.49 30.3
* ND = Not Detected at Reporting Limit Table 3: Headspace GC-MS Analysis of Volatile Organic Compounds (VOC)
Solvent Compounds Detected Retention Time
(min)
Results
(g/l) CAS #
Purified Water
Acetaldehyde 1.32 10.9 75-07-0
Ethyl Alcohol 1.94 42.5 64-17-5
Acetone 2.24 20.9 67-64-1
Isopropyl alcohol 2.43 1387 67-63-0
Trimethylsilanol 4.66 259 1066-40-6
Unknown 5.04 11.3 N/A
70% Ethanol
Trimethylsilanol 4.74 15641 1066-40-6
Hexamethylcyclotrisiloxane 10.4 3500 541-05-9
Unknown 14.2 3319 N/A
FLS-5224VSr2 www.biopharm.saint-gobain.com Page 19 Sani-Tech® STHT®-R Tubing November 1, 2016
Table 4: GC-MS Analysis of Semi-Volatile Organic Compounds (SVOC)
Solvent Compounds Detected Retention
Time (min)
Results
(g/l) CAS #
Purified Water None
70% Ethanol
1,1-Diethoxyethane 5.23 12.2 105-57-7
Diethoxydimethylsilane 6.03 91.3 78-62-6
2,2-Diethoxypropane 6.27 36.7 126-84-1
Hexamethylcyclotrisiloxane 7.35 9.69 N/A
Unknown 7.40 23.6 N/A
1,3-Diethoxy-1,1,3,3-disiloxane 10.5 74.8 18420-09-2
Silicic acid, diethyl bis(trimethylsilyl)
ester 14.2 17.8 3555-45-1
Decamethylcyclopentasiloxane 14.4 21.3 541-02-6
Dodecamethylcyclohexasiloxane 17.6 11.1 540-97-6
Table 5: LC-MS Analysis of Non-Volatile Organic Compounds (NVOC)
Solvent Compounds Detected Retention Time (min)
Results
(g/l) CAS #
Purified Water None
70% Ethanol
Myristic Acid 4.80 2.13 544-63-8
Palmitic Acid 5.97 3.53 57-10-3
Oleic Acid 6.41 0.954 112-80-1
Stearic Acid 7.17 2.45 57-11-4
Erucamide 7.32 4.76 112-84-5
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Table 6: LC-UV Analysis of Non-Volatile Organic Compounds (NVOC)
Solvent Additional Peaks Retention Time
(min) Wavelength (nm)
Purified Water None NA NA
70% Ethanol Yes 3.86 222
FLS-5224VSr2 www.biopharm.saint-gobain.com Page 21 Sani-Tech® STHT®-R Tubing November 1, 2016
4.0 Revisions to FLS-5224VS Sani-Tech® STHT®-R Validation Summary
4.a. Revisions 3.23.15: (.r1)
Front Cover: Updated date and revision number, added product name to footer
Table of Contents: Removed Regulatory Information Overview (RIO) statement. Added Technical Summary. Adjusted
page numbers.
3o. Removed Regulatory Information Overview (RIO) statement. Added Technical Summary
4.0: Added new tests: Biological Reactivity Tests, In Vitro: MEM Elution – Post-Gamma Irradiation; Extractables: Post-Steam Sterilization; Extractables: Post-Gamma Irradiation 6.0 Added new Revisions section
4.b. Revisions 10.31 16: (.r2)
Front Cover: Updated date and revision number, changed product type from hose to tubing
Table of Contents: Removed Technical Summary, Total Carbon Analysis, Extractables, Extractables- Post-Gamma
Irradiation and Metals Analysis by ICP-MS. Added Semi-Quantification and Identification of Extractables: Post-Steam
Sterilization and Semi-Quantification and Identification of Extractables: Post-Gamma Sterilization. Adjusted page
numbers.
3.0 Removed Technical Summary, Total Carbon Analysis, Extractables, Extractables -- Post-Gamma Irradiation, Metals
Analysis by ICP-MS
3.0 Added Semi-Quantification and Identification of Extractables: Post-Steam Sterilization and Semi-Quantification and Identification of Extractables: Post-Gamma Sterilization.