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Biocompatibility/Biostability

Biocompatibility/Biostability www.estane.com 06/07
Biocompatibility/Biostability www.estane.com 06/07

www.estane.com

06/07

Evaluation of Biocompatibility

Lubrizol tested three classes of medical-grade polyurethane resins – Tecoflex ® , Tecothane ® and Carbothane ® – for biocompatibility and biostability. Tecoflex ® TPUs comprise a group of aliphatic polyether-based polyurethanes offered in eight standard grades. Tecothane ® TPUs comprise a group of aromatic polyether-based polyurethanes offered in six standard grades. Carbothane ® TPUs comprise a group of five standard grades of aliphatic polycarbonate-based polyurethanes. The three classes of resins have been evaluated for biocompatibility and biostability using standard biological toxicity tests in addition to long-term implants. Biocompatibility tests were performed using procedures recommended by the Tripartite Commission for medical devices in contact with blood and tissue. Biostabilities of the resins were evaluated by physical property measurements and SEM (scanning electron microscopy) observations of the materials before and after implantation into living tissue. The test materials were extruded into tapes and rods using processing conditions recommended by Lubrizol. The materials were ETO sterilized prior to testing. This was done in order to conform to common fabrication and sterilization procedures used for polyurethane medical device components. The biocompatibility tests were performed by Toxicon Inc. (Bedford, MA). Complete test procedures and results are available upon request to The Lubrizol Corporation.

Biocompatibility Testing

MEM ELUTION TESTING: The biological reactivity of mammalian monolayers towards the test samples was determined. Minimum Essential Medium (MEM) extracts of extruded tape were layered onto L-929 mouse fibroblast cells grown on a solid support. No evidence of toxicity above the negative control material was observed for the Tecoflex ® , Tecothane ® or Carbothane ® resins.

HEMOLYSIS TESTING: Samples of extruded tape were extracted in saline per USP guidelines. Whole rabbit blood was then added to the extracts and the percent of hemolysis was determined. All Tecoflex ® , Tecothane ® and Carbothane ® materials were considered non-hemolytic.

USP CLASS VI TESTING: The USP Class VI testing includes three tests:

1) The Acute Systemic Test involves systemically injecting saline, ethanol, polyethylene glycol and cottonseed oil extracts of the test materials into mice. Injections of the Tecoflex ® , Tecothane ® and Carbothane ® extruded tape extracts showed no evidence of toxicity. 2) The Acute Intracutaneous Test involves intracutaneously injecting saline, ethanol, polyethylene glycol and cottonseed oil extracts of the test materials into rabbits. Injections of the Tecoflex ® , Tecothane ® and Carbothane ® extruded tape extracts showed no evidence of erythema, edema, eschar or clinical toxicity. 3) The Implant Test involves implanting a 1 mm x 1 cm rod of the test material into the paravertebral muscle of a rabbit for 7 days. No signs of hemorrhage, inflammation, necrosis, discoloration or encapsulation were associated with the Tecoflex ® , Tecothane ® or Carbothane ® intramuscular implants compared to the USP negative control strips.

HISTOPATHOLOGY: Samples of all Tecothane ® grades, all Carbothane ® grades and Tecoflex ® EG-60D were subcutaneously implanted into New Zealand rabbits for up to 90 days. Explanted samples were histologically evaluated by a pathologist. The test considered the following biological reaction categories: inflammation, encapsulation, hemorrhaging, necrosis and discoloration. Tecothane ® , Carbothane ® and Tecoflex ® EG-60D materials meet the requirements for the Implantation Test under the Biological Tests for Plastics Section. Rods of Tecoflex ® EG-80A and EG-93A were subcutaneously implanted into New Zealand rabbits for 30 days. Explant samples were examined macroscopically considering the following biological reaction categories: inflammation, encapsulation, hemorrhaging, necrosis and discoloration. Tecoflex ® EG-80A and EG-93A meet the requirements for the Implantation Test under the Biological Tests fot Plastics Section.

MUTAGENICITY TESTING: A representative from each class of the polyurethanes was chosen and evaluated for mutagenicity using the Ames Mutagenicity Assay. Tecoflex ® EG-80A and EG-60D, Tecothane ® TT-1095A and Carbothane ® PC-3595A TPU materials were selected to represent their respective class of materials. Extracts of the extruded Tecoflex ® , Tecothane ® and Carbothane ® tapes were scored as non-mutagenic.

Biostability Testing

30-DAY AND 90-DAY SUBCUTANEOUS TESTING: All Tecothane ® and Carbothane ® implant samples were punched from 0.5 mm thick extruded tape using an ASTM D-1708 die. The approximately 1 cm x 3 cm samples were ETO or chemically sterilized prior to implantation. The samples, along with USP-polyethylene controls, were placed at the dorsal sites above the paravertebral muscle of mature New Zealand white rabbits. Each rabbit received 2 controls and 6 test implants (4 left side, 4 right side). Tecothane ® and Carbothane ® samples were explanted after 30 and 90 days. The explants were evaluated in terms of ultimate tensile strength, ultimate elongation and surface appearance. Tensile and elongation measurements of the explants were tested with control samples conditioned in the same manner but not implanted. The explant samples were examined by scanning electron microscopy to determine if the surface of the material showed signs of degradation.

Tecoflex ® Resin Results

BIOCOMPATIBILITY: Two basic types of medical-grade polyurethanes are manufactured under the Tecoflex ® trademark. Both types of resins are made using the same diisocyanate (HMDI), the same chain extender (BDO) and the same additives (catalyst, antioxidant and lubricant). The difference is that the EG-80A and EG-85A resins use a PTMEG-2000 molecular weight polyol component while the EG-93A, EG-100A, EG-60D, EG-65D, EG-68D and EG-72D use a PTMEG-1000 molecular weight polyol component. Within a given resin type (PTMEG-1000 or PTMEG-2000) all reacting chemicals are the same. Only the ratios of the raw materials change in order to vary the hardness (durometer) of the urethane polymer. Therefore, there is no difference in biocompatibility between EG-80A and EG-85A. Nor is there a difference in biocompatibility among EG-93A, EG-100A, EG-60D, EG-65D, EG-68D and EG-72D. By the same token, blends of the resins within a given resin type have the same biocompatibility as the pure resin. For these reasons, Lubrizol has performed extensive biological testing on one resin from each type. We chose EG-80A and EG-60D as representative resins. All other Tecoflex ® resins fall within the same type as EG-80A or EG-60D. The biocompatibility test results for EG-80A and EG-60D are tabulated in Table 1. The remaining durometers of resin have been checked for their biocompatibility in terms of cytotoxicity (MEM). The results of MEM Elution testing are found in Table 2. All the Tecoflex ® resins passed the MEM Elution test.

The long-term biocompatibility of several Tecoflex ® materials has been evaluated. Tecoflex ® EG-60D passed a 90-day implant. Rod samples of EG-60D were implanted in the paravertebral muscles of rabbits for 7, 21 and 90 days. Microscopic examination of the 7, 21 and 90 day implanted samples were found to have no significant differences in pathologic findings when compared to a USP negative reference plastic. Rods of Tecoflex ® EG-80A, EG-93A and EG-60D were implanted for 30 days in paravertebral muscles of rabbits. These resins meet the requirements of USP XXII for Macroscopic Evaluation.

Table 1 Tecoflex ® EG-80A, EG-93A and EG-60D Biocompatibility Test Results – Including 30-Day and 90-Day Biocompatibility Results

TEST

MATERIAL

MEM

USP CLASS VI 1

30-DAY

90-DAY

AMES

ELUTION

HEMOLYSIS

IMPLANT

IMPLANT

MUTAGENICITY

EG 80A

PASS

PASS

PASS

PASS 2

PASS

EG-93A

PASS

PASS 2

EG-60D

PASS

PASS

PASS

PASS 2

PASS

PASS

1 USP Class VI includes three tests:

1. Systemic injection of 4 extracts; 2. Intracutaneous injection of 4 extracts 3. Intramuscular implantation for 7 days 2 Macroscopic observation of 30-day subcutaneous explants passed gross observation criteria for inflammation, encapsulation, hemorrhaging, necrosis and discoloration.

Table 2 MEM Elution Results for Tecoflex ® Resins

RESIN

EG-80A

EG-85A

EG-93A

EG-100A

EG-60D

EG-65D

EG-68D

EG-72D

MEM

PASS

PASS

PASS

PASS

PASS

PASS

PASS

PASS

RESULTS

Tecothane ® Resin Results

BIOCOMPATIBILITY: The biocompatibility results from the MEM Elution, Hemolysis and USP Class VI tests for the six Tecothane ® grades of resins are shown in Table 3. All materials passed the battery of tests. Also included in Table 3 are the histopathology results for the 30- and 90-day implants included in the biostability study. The results of the 30-day and 90-day subcutaneous implant studies showed a non-inflammatory response to the Tecothane ® implants. There were no signs of hemorrhage or necrosis in any implant. The number of macrophages and giant cells was negligible in all implants indicating no chronic inflammation at the 30-day or 90-day time point. The scores were consistently lower at the 90-day time point, due mostly to a decrease in fibrosis. This is indicative of normal tissue remodeling following a foreign body implantation when there is no chronic inflammation. The Tecothane ® samples were within one scoring point of the USP polyethylene controls in all categories at 30 and 90 days, indicating its biocompatibility as a soft-tissue implant material for up to 90 days.

BIOSTABILITY: The Tecothane ® explants from the 30-day and 90-day subcutaneous implant study were retrieved and evaluated in terms of ultimate tensile strength and elongation. The explanted samples were compared with control samples which had been treated in exactly the same manner as the test samples except that they had not undergone implantation. The results indicate that the bulk properties of Tecothane ® polurethanes remain unaffected by the physiological environment during a 90-day implant period. The data for the Tecothane ® results are presented in Table 4. Electron micrographs were taken to determine if any surface biodegradation of the explanted Tecothane ® materials had occurred. The electron micrographs showed no change in surface morphology after 90 days of implantation for the TT-1095A, TT-1055D, TT-1065D and TT-1075D. The TT-1074A and TT-1085A materials showed some minor surface pitting and cracks after 90 days. The physical test data and electron micrographs for Tecothane ® materials explanted at 30 and 90 days indicate that the TT-1095A, TT-1055D, TT-1065D and TT-1075D materials may be biostable implant materials for up to 90 days. Due to the minor biodegradation observed at 90 days, it is recommended that the TT-1074A and TT-1085A materials be considered only in acute and short-term applications where biostability has been confirmed for the specific application.

Table 3 Tecothane ® Biocompatibility Test Resuts – Including 30-Day and 90-Day Histopathology Results.

TEST

MATERIAL

MEM

USP CLASS VI 1

30-DAY

90-DAY

AMES

ELUTION

HEMOLYSIS

IMPLANT

IMPLANT

MUTAGENICITY

TT-1074A

PASS

PASS

PASS

PASS

PASS

TT-1085A

PASS

PASS

PASS

PASS

PASS

TT-1095A

PASS

PASS

PASS

PASS

PASS

TT-1055D

PASS

PASS

PASS

PASS

PASS

PASS

TT-1065D

PASS

PASS

PASS

PASS

PASS

TT-1075D

PASS

PASS

PASS

PASS

PASS

1 USP Class VI includes three tests:

1. Systemic injection of 4 extracts; 2. Intracutaneous injection of 4 extracts 3. Intramuscular implantation for 7 days

Table 4 Tecothane ® Biostability Data – Tensile Strength and Elongation of 30-Day and 90-Day Implants and the Corresponding Controls.

 

30-DAY IMPLANTS

 

90-DAY IMPLANTS

 

MATERIAL

CONTROL

EXPLANTS

CONTROL

EXPLANTS

Ult. Ten.

Elong.

Ult. Ten.

Elong.

Ult. Ten.

Elong.

Ult. Ten.

Elong.

(psi)

(%)

(psi)

(%)

(psi)

(%)

(psi)

(%)

TT-1074A

3984

602

4522

626

3965

598

3818

600

TT- 1085A

5168

528

6175

575

4998

499

5054

543

TT- 1095A

6004

347

6003

360

6251

336

6351

347

TT- 1055D

6547

308

6266

313

6855

300

6216

285

TT- 1065D

6705

250

6582

255

6462

222

6692

222

TT-1075D

6432

214

6293

212

6127

198

5470

150

Carbothane ® Resin Results

BIOCOMPATIBILITY: The biocompatibility results from the MEM Elution, Hemolysis, USP Class VI tests for the five Carbothane ® grades of resins are shown in Table 5. All materials passed the battery of tests. Also included in Table 5 are the histopathology results for the 30-day and 90-day implants. The results of the 90-day subcutaneous implant studies showed a non-inflammatory response to the Carbothane ® implants. There were no signs of hemorrhage or necrosis in any implant. The numbers of macrophages and giant cells were negligible in all implants indicating no chronic inflammation at the 90-day time point. The Carbothane ® samples were within one scoring point of the USP polyethylene controls in all categories at 90 days, indicating its biocompatibility as a soft-tissue implant material for up to 90 days.

BIOSTABILITY: The Carbothane ® explants from the 30-day and 90-day subcutaneous implant study were retrieved and evaluated in terms of ultimate tensile strength and elongation. The explanted samples were compared with control samples which had been treated in exactly the same manner as the test samples except that they had not undergone implantation. The results indicate that the bulk properties of Carbothane ® polyurethanes remain unaffected by the physiological environment during a 90-day implant period. The data for the Carbothane ® resins are presented in Table 6. Electron micrographs were taken to determine if any surface biodegradation of the explanted Carbothane ® materials had occurred. The electron micrographs showed no change in surface morphology after 90 days of implantation for the PC-3575A, PC-3585A, PC-3595A, PC-3555D and PC-3572D. The physical test data and electron micrographs for Carbothane ® materials explanted after 90 days indicate that the PC-3575A, PC-3585A, PC-3595A, PC-3555D and PC-3572D materials may be biostable implant materials for up to 90 days.

Table 5 Carbothane ® Biocompatibility Test Results – Including 30-Day and 90-Day Histopathology Results.

TEST

MATERIAL

MEM

USP CLASS VI 1

30-DAY

90-DAY

AMES

ELUTION

HEMOLYSIS

IMPLANT

IMPLANT

MUTAGENICITY

PC-3575A

PASS

PASS

PASS

PASS

PASS

PC-3585A

PASS

PASS

PASS

PASS

PC-3595A

PASS

PASS

PASS

PASS

PASS

PC-3555D

PASS

PASS

PASS

PASS

PC-3572D

PASS

PASS

PASS

PASS

PASS

1 USP Class VI includes three tests:

1. Systemic injection of 4 extracts; 2. Intracutaneous injection of 4 extracts 3. Intramuscular implantation for 7 days

Table 6 Carbothane ® Biostability Data – Tensile Strength and Elongation of 30-Day and 90-Day Implants and the Corresponding Controls.

 

30-DAY IMPLANTS

 

90-DAY IMPLANTS

 

MATERIAL

CONTROL

EXPLANTS

CONTROL

EXPLANTS

Ult. Ten.

Elong.

Ult. Ten.

Elong.

Ult. Ten.

Elong.

Ult. Ten.

Elong.

(psi)

(%)

(psi)

(%)

(psi)

(%)

(psi)

(%)

PC-3575A

4691

508

3888

510

4253

458

4230

490

PC-3585A

4587

326

5270

410

5694

350

5888

386

PC-3595A

5339

283

5443

295

6807

263

6988

294

PC-3555D

5132

226

5793

257

6331

225

7333

255

PC-3572D

6364

180

6242

167

7132

118

7028

140

Lubrizol Advanced Materials, Inc. disclaims any warranty of its products (Tecoflex ® , Tecothane ® , Carbothane ® , Tecoplast ® , Tecophilic ® and Tecogel ® ) for merchantability or fitness for any particular application. Any person who intends to use these resins in the manufacture of implantable or any other medical device must independently determine the suitability of these resins for such applications. Each person is responsible for obtaining all necessary FDA and other approvals for the use of these resins in such an application and for complying with all applicable laws relating to the manufacture and sale of medical devices.

ISO 10993 Biocompatibility and Biostability Studies Three classes of Lubrizol medical-grade polyurethane resins –

ISO 10993 Biocompatibility and Biostability Studies

Three classes of Lubrizol medical-grade polyurethane resins – Tecoflex ® , Tecothane ® , and Carbothane ® – were evaluated for biocompatibility and biostability in accordance with ISO 10993 standards. Tecoflex ® is a family of aliphatic polyether-based polyurethanes offered in seven standard grades. Tecothane ® is a family of aromatic polyether-based polyurethanes offered in eight standard grades. Carbothane ® is a family of five standard grades of aliphatic polycarbonate-based polyurethanes. Tecoplast ® , an aromatic polyether-based resin specifically designed for molding applications, was submitted for MEM testing only.

Representative samples from each of the families were selected (See Note 1) and tested in accordance with the various ISO test procedures identified inside. All test materials were extruded into tapes and rods using processing conditions recommended by Lubrizol. These samples were ETO sterilized prior to testing. This was done in order to conform to common fabrication and sterilization procedures used for polyurethane medical device components.

The resins were tested in accordance with the International Organization for Standardization, Biological Evaluation of Medical Devices. The tests were performed by Toxicon Inc. (Bedford, MA, USA). Complete test procedures and results are available upon request to The Lubrizol Corporation.

USA). Complete test procedures and results are available upon request to The Lubrizol Corporation. www.estane.com 06/07

www.estane.com

06/07

BIOCOMPATIBILITY

TESTING

MEM Elution Testing:

This study was conducted based on the procedures described in ISO 10993 – Part 5, (1999); Tests for In Vitro Cytotoxicity.The tests were performed on all clear, standard grades of Tecoflex ® , Tecothane ® , Carbothane ® , and Tecoplast ® resins.

The biological reactivity of mammalian monolayers towards test samples was determined. Minimum Essential Medium (MEM) extracts of extruded tape were layered onto L-929 mouse fibroplast cells grown on a solid support.

No evidence of toxicity above the negative control material was observed for Tecoflex ® , Tecothane ® , Carbothane ® or Tecoplast ® resins.

Indirect Hemolysis Testing:

The assays were conducted based on the procedures described in ISO 10993 – Part 4, (1992); Selection of Tests for Interactions with Blood. Extraction procedures were based upon ISO standard 10993-12(1996).

After an incubation period, fresh diluted rabbit blood was then added to the extracts and the percent hemolysis was determined.

All Lubrizol test articles were considered non-hemolytic.

In Vitro Hemocompatibility:

This test was conducted in accordance ISO 10993 – Part 4 (1992); Selection of Tests for Interactions with Blood.

The test articles were evaluated for their potential to adversely affect selected hematological parameters of human blood in comparison with two controls; untreated control and blood exposed to the negative control article (Negative Control Plastic). The hematological parameters evaluated were Complete Blood Count (CBC), Hematocrit, Erythrocyte indices, Platelet count and Plasma Hemoglobin. The test articles did not have any adverse effects on any of the hematological parameters tested.

All Lubrizol test articles passed the test for in vitro hemocompatibility under the experimental conditions employed.

Systemic Injection Study – ISO (2 extracts):

The test was conducted in accordance with ISO 10993 – Part 11 (1993); Tests for Systemic Toxicity. Extraction procedures were based upon ISO standard 10993-12 (1996).

The extracts were injected i.v. (intravenous) (0.9% USP Sodium Chloride – NaCl) and i.p. (intraperitoneal) (Cottonseed Oil – CSO) in groups of 5 mice. Similarly, groups of 5 mice were injected with the control articles (vehicles). The animals were observed for signs of biological reactivity for 72 hours post inoculation. None of the animals injected with NaCl or CSO extracts, or the control articles (vehicles) exhibited any signs of toxicity through the observation period.

All Lubrizol test articles meet the requirements for the Systemic Injection Test.

Intracutaneous Test/2 Extracts:

The test was conducted in accordance with ISO 10993 – Part 10 (1995); Tests for Irritation and Sensitization Tests. Extraction procedures were based upon ISO standard 10993-12 (1996).

The Intracutaneous Test is designed to evaluate local responses to the extracts of the test articles, following intracutaneous injection into rabbits. The test sites injected with the test article extracts did not exhibit any signs of erythema, edema or necrosis through the seventy-two hour observation point. The primary Irritation Index for both NaCl and CSO extracts of the test articles was 0.0.

The Lubrizol test articles are considered a negligible irritant.

Pyrogen Test:

The tests were conducted in accordance with ISO 10993 – Part 11 (1993); Tests for Systemic Toxicity and upon the standards set by the current version of the United States Pharmacopia. Extraction procedures were based upon ISO standard 10993-12 (1996).

The purpose of this test is to detect the risk to a patient of a febrile reaction as a result of the administration of the test article extracts. Extracts of Tecoflex ® EG-80A, EG-60D, Tecothane ® TT-1085A, Carbothane ® PC-3585A were administered by intravenous injection.

None of the rabbits injected with the test article extract exhibited any signs of pyrogenic response.

All Lubrizol test articles meet the requirements for the absence of pyrogens as specified for the Pyrogen Test.

Physiochemical Test for Plastics:

The tests were conducted in accordance with United States Pharmacopoeia 24, National Formulary 19, pp. 1932 – 1933, 2000.

The test articles were extracted in sterile Water for Injection (WFI), after rinsing in WFI and drying. Non-volatile Residue, Residue on Ignition, Heavy Metals and Buffering Capacity Tests were conducted in order to determine physical and chemical properties of the test articles and their extracts.

All Lubrizol test articles pass USP 24 Physiochemical Test for Plastics based upon the methods used.

BIOSTABILITY TESTING

Implantation Test; 2-week with Histopathology:

These tests were conducted in accordance with ISO standards 10993 – Part 6 (1994); Tests for Local Effects After Implantation.

The Implantation Test is designed for the evaluation of plastic material in direct contact with living tissue. Five strips of the test articles (1 x 1 x 10mm sterilized with a 70% v/v Ethanol solution) were implanted into the paravertebral muscles using a hypodermic needle. Five strips of Negative Control Plastics were also implanted. The excised implant sites were examined for the following biological reactions; inflammation, fibrosis, hemorrhage, necrosis, degeneration foreign debris and relative size of the involved area.

The results of macroscopic observations showed no signs of inflammation, encapsulation, hemorrhaging, necrosis, or discoloration were observed for any of the Lubrizol test articles. Microscopic evaluations of the test article implant sites did not show any increase in Biological reaction as compared to the control article sites at a 14 Day time period.

All Lubrizol test articles meet the ISO 10993-12 requirements for the Tests for Local Effects After Implantation.

See Testing Summary on back

TESTING SUMMARY

MEM Elution Test Results: ISO 10993-5

Tecoflex ®

Strips

EG-80A

Pass

EG-85A

Pass

EG-93A

Pass

EG-100A

Pass

EG-60D

Pass

EG-65D

Pass

EG-72D

Pass

Tecothane ®

Strips

TT-1074A

Pass

TT-1085A

Pass

TT-1095A

Pass

TT-1055D

Pass

TT-1065D

Pass

TT-1069D

Pass

TT-1072D

Pass

TT-1075D-M

Pass

Carbothane ®

Strips

PC-3575A

Pass

PC-3585A

Pass

PC-3595A

Pass

PC-3555D

Pass

PC-3572D

Pass

Tecoplast ®

Strips

TP-470-000

Pass

Biocompatibility and Biostability Test Results

Tecoflex ®

Tecoflex ®

Tecothane ®

Carbothane ®

EG-80A TPU

EG-60D TPU

TT-1085A TPU

PC-3585A TPU

Hemolysis

Pass

Pass

Pass

Pass

ISO 10993-4

Systemic

Injection

Pass

Pass

Pass

Pass

ISO 10993-11

Intracutaneous Test

 

ISO 10993-10

Pass

Pass

Pass

Pass

Implantation – 2 Week ISO 10993-6

Pass

Pass

Pass

Pass

Pyrogen

Pass

Pass

Pass

Pass

ISO 10993-11

In Vitro Hemocompatibility ISO 10993-4

Pass

Pass

Pass

Pass

Physiochemical

Pass

Pass

Pass

Pass

USP 24

NOTES:

1) The test articles used for all the tests, with the exception of the MEM tests, were Tecoflex ® EG-80A, Tecoflex ® EG-60D, Tecothane ® TT-1085A and Carbothane ® PC-3585A TPUs. Two versions of Tecoflex ® TPUs were used for testing as there are two basic types of medical-grade polyurethanes under the Tecoflex ® trademark. Both types of resins are made using the same diisocyanate (HMDI), the same chain extender (BDO) and the same additives (catalysts, antioxidant and lubricant). The difference is that the EG-80A and EG-85A resins use a PTMEG-2000 molecular weight polyol component while the EG-93A, EG-100A, EG-60D, EG-65D and EG-72D use a PTMEG-1000 molecular weight polyol. Within a given type of resin (PTMEG-1000 or PTMEG-2000) all reacting chemicals are the same. Only the ratios of the raw materials change in order to vary the hardness (durometer) of the urethane polymer. Therefore, there is no difference in biocompatibility between EG-80A and EG-85A. Nor is there any difference in biocompatibility among EG-93A, EG-100A, EG-60D, EG-65D and EG-72D. By the same token, blends of the resins within a given resin type have the same basic biocompatibility as the pure resin.

2) Lubrizol Advanced Materials, Inc. disclaims any warranty of its products (Tecoflex ® , Tecothane ® , Carbothane ® , Tecoplast Tecophilic ® and Tecogel ® ), for merchantability or fitness for any particular application. Any person who intends to use these resins in the manufacture of implantable or any other medical device must independently determine the suitablilty of these resins for such applications. Each person is responsible for obtaining all necessary FDA and other approvals for the use of these resins in such an application and for complying with all applicable laws relating to the manufacture and sale of medical devices.

®

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