AseptiQuik G HT Connectors. Product Validation Report

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1 AseptiQuik G HT Connectors Product Validation Report Revision Date:

2 TABLE OF CONTENTS Validation Report Overview... 3 Product Specifications... 6 Microbial Ingress Test... 7 Bacterial Challenge...59 Helium Leak Test...63 Burst Test...65 Side Load Test...66 Creep Rupture Test...68 Tensile Test...70 Flow Test...71 Freeze Thaw Test...72 Systemic Injection Test (USP 88/ISO )...73 Intracutaneous Injection Test (ISO )...87 Intramuscular Implantation Test (ISO ) Physico-Chemical Test (USP 661) Elastomeric Closures for Injection (USP381) Hemolysis (ASTM F756-00) L929 MEM Elution Test (ISO and USP 87) Membrane Systemic Toxicity (ISO ) Membrane Intracutaneous Injection (ISO ) Membrane L929 MEM Elution Test (ISO ) Material Content Statement Cleanliness Statement Shelf Life and Storage Conditions Legal Statements Page 2 of 166

3 VALIDATION REPORT OVERVIEW Genderless AseptiQuik G HT Connectors enable quick and easy sterile connections, even in non-sterile environments. The easy-to-use genderless design simplifies system integration and minimizes the risk of operator error. The connector s robust construction provides enhanced user confidence and reliable performance without the need for clamps, fixtures or tube welders. Biopharmaceutical manufacturers benefit from a full range of interchangeable 1/4 to 3/4 flow solutions with the quality and market availability they expect from the leader in single-use connection technology. This report is intended to document testing that has been performed on AseptiQuik G HT Connectors. This information is valid for the following part numbers: Part Number AQG17004HT AQG17006HT AQG17008HT AQG17012HT AQG33012HT Description AseptiQuik G HT Body with 1/4 Hose Barb AseptiQuik G HT Body with 3/8 Hose Barb AseptiQuik G HT Body with 1/2 Hose Barb AseptiQuik G HT Body with 3/4 Hose Barb AseptiQuik G HT Body with 3/4 Sanitary For additional information on the AseptiQuik G HT Connectors, please contact your CPC representative. Page 3 of 166

4 SUMMARY OF TESTING: Microbial Ingress Test: AseptiQuik G HT Connectors were subjected to three types of bacterial ingress challenges (Dip, Spray and Immersion) to verify the integrity of the AseptiQuik Connectors. Halves were pre-sterilized with gamma (minimum 50kGy) prior to testing. Additional samples were autoclaved once at 130C for 60 minutes with a 15 minute dry time. The challenge organism selected for all three ingress methods was Brevundimonas diminuta at a final concentration of approximately 1 x 10 8 CFU/mL. Dip Method Each half of the connector was dipped into the challenge organism prior to connection on the membrane side. The dipped parts where then fully connected and then submerged in the challenge organism. After submersion, the growth media was introduced to each assembled connector by flushing it through the connectors and collected. Spray Method with Immersion Test Each half of the connector was sprayed on the membrane side with the challenge organism prior to connection. The halves where then connected and while the membrane was removed a 2 nd spray was applied to the top of the connectors. After removal of the membranes, the parts where then submerged in the challenge organism. After submersion, the growth media was introduced to each assembled connector by flushing it through the connectors and collected. Results of the three challenges show the units tested negative for bacterial ingress of the indicator organism after a seven day incubation period at 30-35ºC. Helium Leak Test: Helium Leak Tests were completed on connected AseptiQuik G HT Connectors that were gamma irradiated to 50 kgy and autoclaved twice at 130ºC for 60 minutes per cycle with a 15 minute dry time to demonstrate sealing performance at the temperature extremes of 1ºC (39ºF) and 40ºC (104ºF) and pressures of 5 psi (0.35 bar) and 75 psi (5.1 bar). Results show that all the test units passed the leak limit of 1.0 x 10-5 atm-cc/sec. Burst Test: To demonstrate that connected AseptiQuik G HT Connectors maintain an adequate margin of safety above the rated operating pressures of 75 psi (5.1 bar) after gamma sterilization (50 kgy nominal). Parts were also autoclaved twice at 130ºC for 60 minutes. The connectors were then pressurized until a leak was observed. All measured burst pressures observed were above the minimum acceptable level of 130 psi (9 bar). Side Load Test: To demonstrate that connected AseptiQuik G HT Connectors remain leak free while side load is applied to the hose barb termination after gamma sterilization (50 kgy nominal) and two autoclave cycles at 130ºC for 60 minutes. Connected AseptiQuik G HT Connectors were subjected to a 15lbf (for 1/4 HB only) or 25lbf side load force in three different directions to ensure that the product still provides a seal at 5 psi and 75 psi of pressure as well as under vacuum. Page 4 of 166

5 Flow Test: The Flow Test was conducted in order to determine the Cv of the AseptiQuik Connector. The Cv value for the 1/4 HB Connectors was determined to be 1.5. The Cv value for the 3/8 HB Connectors was determined to be 5.6. The Cv value for the 1/2 HB Connectors was determined to be The Cv value for the 3/4 HB Connectors was determined to be The Cv value for the 3/4 SANI Connectors was determined to be This value can be used to calculate anticipated flow rates and pressure drops. Biocompatibility Tests: The polycarbonate and platinum cured silicone materials were tested at the same time to USP Class VI criteria. All biocompatibility testing was done on parts after being exposed to 50 kgy of gamma radiation and autoclaved at 135 C (275 F) for 60 minutes. Tests performed include: Systemic Injection, Intracutaneous Injection, Intramuscular Implantation, Cytotoxicity using MEM Elution, Physicochemical studies, and Hemolysis studies. Page 5 of 166

6 PRODUCT SPECIFICATIONS Page 6 of 166

7 MICROBIAL INGRESS TEST Page 7 of 166

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59 BACTERIAL CHALLENGE Page 59 of 166

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63 HELIUM LEAK TEST Page 63 of 166

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65 BURST TEST Page 65 of 166

66 SIDE LOAD TEST Page 66 of 166

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68 CREEP RUPTURE TEST Page 68 of 166

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70 TENSILE TEST Page 70 of 166

71 FLOW TEST Page 71 of 166

72 FREEZE THAW TEST Page 72 of 166

73 SYSTEMIC INJECTION TEST (USP 88/ISO ) Page 73 of 166

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87 INTRACUTANEOUS INJECTION TEST (ISO ) Page 87 of 166

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103 INTRAMUSCULAR IMPLANTATION TEST (ISO ) Page 103 of 166

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125 PHYSICO-CHEMICAL TEST (USP 661) Page 125 of 166

126 ELASTOMERIC CLOSURES FOR INJECTION (USP381) Page 126 of 166

127 HEMOLYSIS (ASTM F756-00) Page 127 of 166

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145 L929 MEM ELUTION TEST (ISO AND USP 87) Page 145 of 166

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158 MEMBRANE SYSTEMIC TOXICITY (ISO ) Page 158 of 166

159 MEMBRANE INTRACUTANEOUS INJECTION (ISO ) Page 159 of 166

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161 MEMBRANE L929 MEM ELUTION TEST (ISO ) Page 161 of 166

162 MATERIAL CONTENT STATEMENT Material Content Statement for AseptiQuik Connectors May 2014 Animal Content The components used in the manufacture of the AseptiQuik product line are free of animal derived ingredients based upon declarations from the material suppliers which state the materials used to produce the components used in AseptiQuik Connectors are free of animal derived ingredients. Furthermore, no animal derived materials are used in the processing of the AseptiQuik product line. Facilities which mold the AseptiQuik wetted components mold other materials which may contain animal derived materials. However, purging processes, high injection pressures and the high molding temperatures (>560F) are expected to eliminate any risk from any polymers that contain animal derived ingredients used in the same equipment. Latex Content CPC has received documentation from its suppliers declaring that all materials in the AseptiQuik product line are free of Latex. RoHS CPC has received documentation declaring that all of the component materials in the AseptiQuik product line are compliant with Directive 2011/65/EU and related amendments with respect to the Reduction of Hazardous Substances (RoHS) in regard to maximum allowable concentrations of PBDEs, PBBs, lead, mercury, hexavalent chromium and cadmium. REACH SVHCs CPC has received documentation declaring that all of the flow path component materials in the AseptiQuik product line are free from substances listed on the ECHA s list of Substances of Very High Concern (SVHC) as intentionally added ingredients or as expected process impurities above concentration limit of 0.1% as of the December 16, 2013 update. Page 162 of 166

163 Melamine CPC has received documentation declaring that all of the flow path component materials in the AseptiQuik product line are free from melamine as an intentionally added ingredient. Phthalates CPC has received documentation declaring that all of the flow path component materials in the AseptiQuik product line do not contain the below listed Phthalates as intentionally added ingredients or as expected process impurities above a concentration limit of 0.1%. Chemical Name CAS number Butyl benzyl phthalate (BBP) Dibutylphthalate (DBP) Bis (2-ethylhexyl) phthalate (DEHP) ,2-Benzebeducarboxylic acid diiscodecyl ester (DIDP) Diisononyl phthalate (DINP) Di-n-octyl phthalate (DNOP) Diisobutyl phthalate (DIBP) Di-N-pentyl phthalate (DNPP) Extractables Testing CPC has performed extractables testing on the flow path component materials used in the AseptiQuik product lines. Please us at info@cpcworldwide.com to request a copy of the report. Page 163 of 166

164 CLEANLINESS STATEMENT Cleanliness Testing Performed on All AseptiQuik Product Lines CPC manufactures the AseptiQuik product lines in an ISO Class 7 cleanroom. In addition to ISO Class 7 specifications, CPC tests product for particulate, bioburden, and endotoxin cleanliness levels during product validation. Please see criteria below. Particulate For items produced in the ISO Class 7 cleanroom CPC has the following particulate requirements. Testing performed per USP<788>. <25 particles / ml for particulates greater than or equal to 10µm in size <3 particles / ml for particulates greater than or equal to 25µm in size Endotoxin For items produced in the ISO Class 7 cleanroom CPC allows a maximum endotoxin content of EU / ml. This test is conducted per USP <85>. Bioburden For items produced in the ISO Class 7 cleanroom CPC allows a maximum microbial load or bioburden content of 10 CFU / 100ml. This test is conducted per USP <1231>. Page 164 of 166

165 SHELF LIFE AND STORAGE CONDITIONS Statement Regarding Storage Conditions and Shelf Life of AseptiQuik G HT Connections The shelf life of a connector is dependent upon the connector materials and the storage conditions. In general, it is best to store any product in an environment shielded from light at a temperature between 50 o F and 90 o F. The shelf life of CPC s AseptiQuik G HT connections is estimated to be 3 years minimum from date of manufacture based on accelerated aging testing, if the storage conditions comply with these shown above. Aging was performed post gamma sterilization. Page 165 of 166

166 LEGAL STATEMENTS Further Information: For additional information regarding the AseptiQuik G HT Connector, please contact CPC or your bag manufacturer/local distributor. CPC Warranty Statement: Colder Products Company warrants its products against defects in workmanship and materials a period of 12 months from the date of sale by CPC to its initial customer (regardless of any subsequent sale of the products). This warranty is void if the product is misused, altered, tampered with or is installed or used in a manner that is inconsistent with CPC s written recommendations, specifications and/or instructions, or fails to perform due to normal wear and tear. CPC does not warrant the suitability of the product for any particular application. Determining product application suitability is solely the customer's responsibility. CPC is not liable for special, indirect, incidental, consequential or other damages including, but not limited to, loss, damage, personal injury, or any other expense directly or indirectly arising from the use of or inability to use its products either separately or in combination with other products. ALL OTHER WARRANTIES EXPRESS OR IMPLIED, WHETHER ORAL, WRITTEN OR IN ANY OTHER FORM, INCLUDING BUT NOT LIMITED TO WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, ARE EXPRESSLY EXCLUDED. CPC Patent Statement: CPC takes pride in its innovative quick disconnect coupling solutions, many of which have been awarded United States and International patents. Colder Products Company has a strong tradition of leadership in the quick disconnect market, and aggressively pursues and protects its proprietary information and intellectual property. In cases where it is practical and as a benefit to its customers, CPC has licensed its proprietary technology. Please contact CPC to discuss your unique needs. Copyright and Trademark Statements: Copyright 2015 by Colder Products Company. All rights reserved. Colder Products Company, Colder Products and CPC are registered trademarks with the US Patent & Trademark Office. Page 166 of 166