SAMPLE REQUIREMENTS FOR BIOCOMPATIBILITY …

1 SAMPLE REQUIREMENTS FOR BIOCOMPATIBILITY testing This chart is designed as a convenient quick guide for some of our most commonly ordered tests (and does not list all available tests). SAMPLE REQUIREMENTS represent total number extracts/replicates needed. For example, Partial Thromboplastin Time requires 3 replicates at 4 cm each. The SAMPLE sizes reflect the minimum amount of SAMPLE , depending on the test being performed. For liquid samples , contact Client Services. Turnaround times for GLP testing are shown in brackets with each test listing. If not GLP testing , turnaround times would be approximately 7 days shorter. If you have questions, before submitting samples , contact Client Services at WuXi AppTec s St. Paul facility: 651-675-2000 or 888-794-0077. TESTS PERFORMED USING EXTRACTION RATIOS < thickness Ratio: 6cm /1mL thickness Ratio: 3cm /1mL Irregularly Shaped Ratio: Membranes/Textiles Ratio.

2 CYTOTOXICITY MEM Elution Using L-929 Mouse Fibroblast Cells ISO/USP [18 days] 1 x 30cm 1 x 15cm 1 x 1g 1 x MEM Endpoint Dilution Using L-929 Mouse Fibroblast Cells [18 days] 1 x 48cm 1 x 24cm 1 x 1 x MTT Cytotoxicity Using L-929 Mouse Fibroblast Cells [26 days] 1 x 36cm 1 x 18cm 1 x 1 x Neutral Red Uptake (NRU) [26 days] 1 x 42cm 1 x 21cm 1 x 1 x GENOTOXICITY Bacterial Mutagenicity (Ames) [28 days] 2 x 24cm 2 x 12cm 2 x 2 x In-Vitro Chromosome Aberration [62 days] 2 x 42cm 2 x 21cm 2 x 2 x In-Vitro Mouse Lymphoma with Extended Treatment [39 days] 2 x 60cm 2 x 30cm 2 x 2g 2 x 1g In-Vivo Mouse Micronucleus [48 days] 2 x 120cm 2 x 60cm 2 x 4g 2 x 2g IRRITATION Intracutaneous Irritation ISO/USP [29 days] 2 x 36cm 2 x 18cm 2 x 2 x Vaginal Mucosal Irritation ISO [54 days] 10 x 60cm 10 x 30cm 10 x 2g 10 x 1g PYROGENICITY Materials Mediated Rabbit Pyrogen ISO [26 days] 900cm 450cm 30g 15g SENSITIZATION Maximization Sensitization (Guinea Pig) ISO [47 days] 6 x 60cm 6 x 30cm 6 x 2g 6 x 1g Murine Local Lymph Node (LLNA) [32 days] 6 x 30cm 6 x 15cm 6 x 1g 6 x SYSTEMIC TOXICITY Acute Systemic Toxicity ISO/USP [27 days] 2 x 48cm 2 x 24cm 2 x 2 x Subchronic Intravenous Toxicity (Mice)

3 5 Dose [82 days] 5 x 48cm 5 x 24cm 5 x 5 x Subacute Intraperitoneal Toxicity (Mice) 5 Dose [82 days] 5 x 30cm 5 x 15cm 5 x 1g 5 x Subchronic Intravenous Toxicity (Mice) 14 Dose [82 days] 14 x 48cm 14 x 24cm 14 x 14 x Subacute Intraperitoneal Toxicity (Mice) 14 Dose [82 days] 14 x 30cm 14 x 15cm 14 x 1g 14 x Subchronic Intravenous Toxicity (Rats) 14 Dose [82 days] 14 x 270cm 14 x 135cm 14 x 9g 14 x Subacute Intraperitoneal Toxicity (Rats) 14 Dose [82 days] 14 x 90cm 14 x 45cm 14 x 3g 14 x MHLW Cytotoxicity Test Colony Microassay by Elution [31 days] 120cm 120cm 2g 2g MHLW Hemolysis [32 days] 3 x 120cm 3 x 60cm 3 x 4g 3 x 2g MHLW Intracutaneous Irritation [29 days] 2 x 36cm 2 x 18cm 2 x 2 x MHLW Primary Skin Irritation [30 days] 2 x 30cm 2 x 15cm 2 x 1g 2 x MHLW Materials Mediated Rabbit Pyrogen [26 days] 900cm 450cm 30g 15g MHLW Acute Systemic Toxicity [27 days] 2 x 48cm 2 x 24cm 2 x 2 x MHLW Subacute Intravenous Toxicity (28 Day / 28 Dose) [105 days] 28 x 600cm 28 x 300cm 28 x 20g 28 x 10g TESTS PERFORMED USING EXHAUSTIVE EXTRACTION METHODS Pretest Method 1 Method 2 MHLW Bacterial Reverse Mutation (Ames Assay) [40 days] 10g The pretest result can be used for any one or all of these tests.

4 TO BE DETERMINED SAMPLE REQUIREMENTS based on the amount of residue obtained in the pretest will be communicated to the client by a WuXi AppTec representative. 1g MHLW In-Vitro Mouse Lymphoma [53 days] 2g MHLW In-Vitro Chromosome Aberration [62 days] 2g MHLW In-Vivo Mouse Micronucleus [48 days] 5g MHLW Maximization Sensitization [81 days] 20g HEMOCOMPATIBILITY / BLOOD COMPATIBILITY TESTS thickness Ratio: 6cm /1mL > thickness Ratio: 3cm /1mL Irregularly Shaped Ratio: Complement Activation C3a and SC5b-9 [25 days] 6cm * 3cm * * Hemolysis: ASTM Direct Contact [21 days] 3 x 42cm 3 x 21cm 3 x Hemolysis: ASTM Extract [21 days] 3 x 60cm 3 x 30cm 3 x 2g In-Vitro Hemocompatibility [25 days] 3 x 12cm * Partial Thromboplastin Time [25 days] 3 x 4cm * Platelet and Leukocyte Count [25 days] 3 x 12cm * Thromboresistance (In-Vivo) [28 days] 1 test SAMPLE and 1 comparison SAMPLE per animal *Concurrent testing of sponsor-supplied comparison product is recommended.

5 (Required for thromboresistance studies.) SAMPLE size of the comparison product should be the same as that of the test article. TESTS PERFORMED USING THE PATCH METHOD (SKIN CONTACTING) Agarose Overlay Using L-929 Cells ISO/USP [14 days] Sufficient material to produce 3 patches, 1cm x 1cm each Primary Skin Irritation ISO [30 days] Sufficient material to produce 7 patches, x each Repeated Patch Dermal Sensitization Test Buehler [57 days] Sufficient material to produce 116 patches, x each IMPLANTATION TESTS (Note: Turnaround times are in addition to implant duration.) Intramuscular/Subcutaneous Implantation (3 Rabbit) ISO [42 days] Sufficient material to produce 15 implants, approx. 10mm x 3mm each Intramuscular/Subcutaneous Implantation (5 Rabbit) ISO [49 days] Sufficient material to produce 25 implants, approx.

6 10mm x 3mm each Intramuscular Implantation USP [21 days] Sufficient material to produce 12 implants, approx. 10mm x 3mm each MHLW Intramuscular / Subcutaneous Implantation [42 days] Sufficient material to produce 20 implants, approx. 10mm x 3mm each 083115