Santoprene Sterilization Study n4z6u

Sterilization Study of Santoprene™ Thermoplastic Vulcanizate Technical Literature - TL00708

Introduction Santoprene thermoplastic vulcanizate (TPV) is a fully crosslinked thermoplastic elastomer (TPE) which has many unique properties over thermoset rubbers and other thermoplastic elastomers. Examples of these advantages are:  Low compression set  Thermoplastic processing  Wide hardness range

Available Grades The current medical grades available are: 281-55MED 8281-35MED 8281-45MED 8281-55MED

Colorable 8281-65MED 8281-75MED 8281-90MED

Black 181-55MED 181-57W180

Product data sheets for these grades can be found at www.santoprene.com. From these unique properties, product designers often incorporate Santoprene TPV in medical devices such as syringe plungers, gaskets, grips and bumpers. When in such devices, these materials will likely be exposed to one of the following sterilization processes:  Ethylene oxide (EtO)  Gamma radiation  Autoclave A key consideration in a medical device is to understand the affects sterilization has on the physical properties of Santoprene TPV.

Scope To better understand how sterilization affects the properties of Santoprene TPV, several grades that span the available hardness were submitted to EtO, gamma radiation and autoclave sterilization, and tested for relevant properties. This technical document reviews the results from this testing. For reference, the retention of a property is calculated by the following equation:

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% Retention = (Property after Aging) / (Property Unaged) * 100 Additional Note: This product, including the product name, shall not be used or tested in any medical application without the prior written acknowledgement of ExxonMobil Chemical as to the intended use.

Ethylene Oxide Sterilization EtO sterilization is a popular method for “one time use” medical disposables that are also only sterilized once. The key property to monitor for this type of sterilization is the retention of residuals (measured in mgs/day) for EtO and ethylene chlorohydrins (ECHs). For this study:  The grades evaluated were 181-57W180, 281-45MED, 281-64MED and 281-87MED.  Plaques of each grade were submitted to two EtO sterilization cycles. Two cycles were used to represent the maximum exposure incurred in typical medical device manufacturing. Exposing a device to a second cycle arises when the first cycle prematurely ends. Exposure to the second cycle ensures the device was exposed to at least one complete cycle. Cycles beyond two are not expected.  Test procedures and allowable residual limits are specified per ISO 10993-7 October 1995.  The procedure for the residual analysis was per ISO 17025. The following additional steps were employed: 1. Test specimens were frozen after sterilization and thawed prior to testing to accurately control aeration time. 2. Residuals were extracted in an eluate by placing the plaques in 20 ml of purified water at 37°C for 24 hours. 3. Residual levels in the eluate were determined by gas chromatography.  Residual levels were measured at one and four days of aeration. Results can be found in Table I. Results were: EtO:

After one day post sterilization, EtO residuals for all grades were well below the maximum allowable limit of 20 mgs/day (per ISO 10993-7) and not detectable after four days.

ECH:

After one day post sterilization, ECH residuals for all grades were less than half the maximum allowable limit of 12 mgs/day (per ISO 10993-7) and below 1.8 mgs/day after four days.

In summary, all grades in this testing exhausted both EtO and ECH residuals well below the maximum allowable limits after only one day of aeration.

Autoclave Autoclaving is a common technique used for sterilizing devices by the individual medical care professional (e.g., doctor’s office, hospital, etc.) for durable medical instruments (scalpels, tongs, pliers, etc.). Autoclaving sterilizes a device by exposing it to super-heated steam (steam heated to temperatures above 100°C and pressures above one atmosphere) for a specific duration (usually a minimum of five minutes at peak temperature and pressure). To evaluate the effect autoclave sterilization has on Santoprene TPV, plaques were submitted to two different sets of autoclave exposures. The first set was for five autoclave exposures. The second set was for 250 autoclave exposures, with samples incrementally pulled and tested at 50, 100 and 250 cycles.

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Autoclave - 0 Cycles The first study (five autoclave exposures) exposed plaques of 281-45MED, 281-64MED, 281-87MED, 8281-45MED, 8281-65MED and 8281-90MED. Autoclave parameters for each of these exposures were: Exposure Temperature: 132°C (270°F) Exposure Time: 30 minutes Exposure Pressure: 28.6 psig Containment: Plaques were placed in plastic bags Parameters measured in the testing were:  % Retention of Hardness  % Retention of Ultimate Tensile Strength  % Retention of Tensile Stress at 100% Elongation  % Retention of Ultimate Elongation

ISO 868 ISO 37 ISO 37 ISO 37

Results can be found in Graph 1 (a-d). Five cycles of autoclaving showed less than 20% effect on ultimate tensile strength and tensile stress at 100% elongation and less than 30% reduction of % elongation for all grades.

Autoclave - 250 Cycles The second study exposed plaques of 281-64MED, 281-73MED and 281-87MED to 250 autoclave cycles. Autoclave parameters in this testing were: Exposure Temperature: 132°C (270°F) Time at Temperature: 6 minutes Time between Exposures: 30 minutes Containment: Plaques were directly exposed to the steam (no bags) Results can be found in Graph 2 (a-d). Properties measured in this testing were:  % Retention of Ultimate Tensile Strength  % Retention of Tensile Stress at 100% Elongation  % Retention of Ultimate Elongation  % Retention of Hardness

ASTM D412 ASTM D412 ASTM D412 ASTM D2240

Two hundred-fifty cycles of autoclaving had little effect on hardness and ultimate tensile strength. The tensile stress at 100% elongation could only be measured for 281-87MED. This is due to the elongation of 281-73MED and 281-64MED going below 100% after 50 cycles. For the 250 cycles of autoclaving, the majority of changes in physical properties occurred in the first 50 cycles.

Gamma Sterilization Gamma sterilization is a method that sterilizes devices by exposing them to controlled dosages of gamma radiation. Gamma sterilization has the advantage of 1) short turn around times, and 2) low cost when

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performed in volume. From these advantages, this method is gaining popularity for many “one time use” medical disposables. Historically, much of the medical industry expressed the amount a device was gamma irradiated in the units of MegaRads (Mrads). Today, the amount a device is exposed to gamma irradiation is expressed in the international standard of KiloGray (KGy). Ten KGy = one Mrads (example: 25 KGy = 2.5 Mrads). A typical irradiation for a medical device for one cycle is 10 to 25 KGy. Should a problem arise during sterilization, the devices may be exposed to a second cycle of up to an additional 25 KGy. Such a second cycle ensures the device was exposed to at least one full cycle. It should be noted the effects of gamma irradiation are cumulative. This means that if the first gamma cycle is 25 KGy and a second cycle of 25 KGy is performed, then the total effect on the device and its materials is the same as the device being exposed to one dose of 50 KGy. For this testing, dosages as high as 70 KGy were evaluated, which is an excessive overexposure for any medical device. From this, all data above 50 KGy should be viewed only for reference. The Santoprene TPV grades selected for this testing were 281-45MED, 281-64MED, 281-87MED, 828145MED, 8281-65MED and 8281-90MED. Parameters measured in testing were:  % Retention of Ultimate Tensile Strength ISO 37  % Retention of Tensile Stress at 100% Elongation ISO 37  % Retention of Ultimate Elongation ISO 37  Changes in Color TPE-0135  Changes in Compression Set ISO 815 Note: Because of limited samples, compression set testing was only conducted on the following grades: 281-45MED, 281-64MED and 8281-65MED. Results can be found in Graph 3 (a-f). All grades showed a gradual change in tensile properties and color for gamma sterilization under 50 KGy. In compression set testing, the 281-45MED and 281-64MED showed little effect from gamma irradiation. The 8281-65MED showed a significant loss (or increase) in compression set. From this, it is suggested that the 8281-XXMED grades may possibly not be suitable for sealing applications that are exposed to 25 KGys or more gamma irradiation.

Summary Santoprene TPV exhibits excellent retention of physical properties after repeated heat histories. The Santoprene TPV grades in the above testing showed excellent performance when sterilized with EtO. Santoprene TPVs released all measured residuals quickly and to levels well below requirements. From five cycles of autoclaving in the above testing, Santoprene TPV showed less than 30% change in properties. From 250 cycles of autoclaving in the above testing, most change in physical properties occurred in the first 50 cycles and was under 30% for the entire test. For gamma sterilization, all grades in this study showed a gradual change in properties and color when irradiated to 50 KGys. 281-XXMED grades showed better property retention in compression set than 8281-XXMED. 8281-XXMED may not be suitable grades for sealing applications requiring 25 KGys or more irradiation.

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Table I

Ethylene Oxide Sterilization - EtO Residuals

Materials Allowable Limit per ISO 10993-7 Santoprene™ 181-57W180 TPV Santoprene 281-45MED TPV Santoprene 281-64MED TPV Santoprene 281-87MED TPV

mgs/day 1 Day 20 <0.18 0.32 0.40 0.35

4 Days 20 <0.18 <0.18 <0.18 <0.18

Note: <0.18 means actual values are below detectable levels.

Ethylene Oxide Sterilization - ECH Residuals Materials Allowable Limit per ISO 10993-7 Santoprene 181-57W180 TPV Santoprene 281-45MED TPV Santoprene 281-64MED TPV Santoprene 281-87MED TPV

mgs/day 1 Day 12 1.554 3.91 4.17 4.13

4 Days 12 1.26 1.48 1.78 0.96

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Graph 1-a % Retention of Ultimate Tensile Strength after 5 Autoclave Cycles

% Retention of Ultimate Tensile Strength

120%

100%

80%

60%

40%

20%

0% 281-45MED

281-64MED

281-87MED

8281-45MED

8281-65MED

8281-90MED

Graph 1-b

% Retention of Tensile Modulus at 100% Elongation

% Retention of Tensile Modulus at 100% Elongation after 5 Autoclave Cycles 120%

100%

80%

60%

40%

20%

0% 281-45MED

281-64MED

281-87MED

8281-45MED

8281-65MED

8281-90MED

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Graph 1-c % Retention of Elongation after 5 Autoclave Cycles 120%

% Retention of Elongation

100%

80%

60%

40%

20%

0% 281-45MED

281-64MED

281-87MED

8281-45MED

8281-65MED

8281-90MED

Graph 1-d

% Retention of Hardness after 5 Autoclaves 120%

% Retention of Hardness

100%

80%

60%

40%

20%

0% 281-45 MED

281-64 MED

281-87 MED

8281-45 MED

8281-65 MED

8281-90 MED

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Graph 2-a % Retention of Hardness vs. Autoclave Cycle 140

% Retention of Hardness

120 100 80 60 40 20 0 0

50

100

150

200

250

300

Number of Autoclave Cycles 281-87MED

281-73MED

281-64MED

Graph 2-b % Retention of Ultimate Tensile Strength vs. Autoclave Cycle

% Retention of Ultimate Tensile Strength

140 120 100 80 60 40 20 0 0

50

100

150

200

250

300

Number of Autoclave Cycles 281-87MED

281-73MED

281-64MED

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Graph 2-c

% Retention of Tensile Modulus at 100% Elongation

% Retention of Tensile Modulus at 100% Elongation vs. Autoclave Cycle 140 120 100 80 60 40 20 0 0

50

100

150

200

250

300

Number of Autoclave Cycles 281-87MED

Note:

The only grade “% retention of tensile stress @ 100% elongation” could be calculated for was 281-87MED, due to 281-64MED and 281-73MED not having a 100% elongation after 50 cycles.

Graph 2-d % Retention of Elongation vs. Autoclave Cycle 140

% Retention of Elongation

120 100 80 60 40 20 0 0

50

100

150

200

250

300

Number of Autoclave Cycles 281-87MED

281-73MED

281-64MED

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Graph 3-a % Retention of Ultimate Tensile Strength vs. Levels of Gamma Exposure

% Retention of Ultimate Tensile Strength

120%

100%

80%

60%

40%

20%

0% 0

10

20

30

40

50

60

70

80

KGy Gamma 281-45 MED

281-64 MED

281-87 MED

8281-45 MED

8281-65 MED

8281-90 MED

Graph 3-b

% Retention of Tensile Modulus at 100% Elongation vs. Levels of Gamma Exposure

% Retention of Secant Modulus at 100%

120% 100% 80% 60% 40% 20% 0% 0

281-45 MED

10

281-64 MED

20

30

281-87 MED

40 KGy Gamma 8281-45 MED

50

60

8281-65 MED

70

80

8281-90 MED

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Graph 3-c

% Retention of Elongation vs. Levels of Gamma Exposure % Retention of Elongation

120% 100% 80% 60% 40% 20% 0% 0

10

20

30

40

50

60

70

80

KGy 281-45 MED

281-64 MED

281-87 MED

8281-45 MED

8281-65 MED

8281-90 MED

Graph 3-d

Color L vs. Levels of Gamma Exposure 90

L Hunter Color Units

80 70 60 50 40 30 20 10 0 0

10

20

30

40

50

60

70

80

KGy 281-45MED

281-64MED

281-87MED

8281-45MED

8281-65MED

8281-90MED

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Graph 3-e

Color B vs. Levels of Gamma Exposure 90

B Hunter Color Units

80 70 60 50 40 30 20 10 0 0

10

20

30

40

50

60

70

80

KGy 281-45MED

281-64MED

281-87MED

8281-45MED

8281-65MED

8281-90MED

Graph 3-f

% Compression Set after 168 hours at 100°C vs. Levels of Gamma Exposure 90 80

% Compresion Set

70 60 50 40 30 20 10 0 0

10

20

30

40

50

60

70

80

KGy 281-45 MED

281-64 MED

8281-65 MED

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