validation guide summary - saint-gobain€¦ · it is sterilizable via autoclave, gamma irradiation...

FLS-5224VSr2 www.biopharm.saint-gobain.com Sani-Tech® STHT®-R Tubing November 1, 2016

Validation Guide Summary

Sani-Tech® STHT®-R Tubing Revision: 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].

mailto:[email protected]


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.


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.


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.


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.


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


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).





3g. USP <87> Biological Reactivity Tests, In Vitro – Agar Diffusion Test



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).




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.


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.


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.


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




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.




Sani-Tech® STHT®-R 7.59 0.004 0.1

3l. USP <643> Total Organic Carbon Analysis – 5 Autoclave Cycles




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






Sani-Tech® STHT®-R 4.19 0.002 0.1

3m. USP <643> Total Organic Carbon Analysis – 10 Autoclave Cycles




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





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.


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>.



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


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.


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.


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


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


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





Table 5: LC-MS Analysis of Non-Volatile Organic Compounds (NVOC)


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


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.


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*


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



70% Ethanol


Hexamethylcyclotrisiloxane 10.4 3500 541-05-9

Unknown 14.2 3319 N/A


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


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)


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


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


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.

validation guide summary - saint-gobain€¦ · it is sterilizable via autoclave, gamma irradiation...

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