Feasibility of Supercritical Carbon Dioxide Sterilization for Absorbable Suture M

描述(申请人提供)：在过去的几十年里，医疗器械灭菌领域的创新相对较少。环氧乙烷(ETO)和 伽马辐照是唯一可用于医疗设备的商业技术。特别是，由于伽马辐射引起的不良化学降解和/或机械变化，合成聚合物医疗设备几乎完全由ETO灭菌。伽马辐照需要钴-60，这些设施通常设在与这项技术相关的运营成本较高的大型工业或研究机构中。由于灭菌产品中残留的ETO的短期和长期负面影响，缝合线制造商表示有兴趣放弃这一过程，因为它是公认的致癌物，而且需要采取预防措施，绕过ETO的毒性和爆炸性。最近，环境保护局和其他政府机构已经开始监测ETO，以应对个人和环境问题。因此，开发能够达到经过验证的10-6(SAL6)无菌保证水平--医疗器械的基准--而不使用危险的ETO或破坏性辐照的替代灭菌工艺是非常重要的。目前提议的努力旨在推进NovaSterilis的超临界二氧化碳(ScCO2)灭菌技术，并生产一种可行的方法，在保持缝合机械性能的同时对缝合材料进行灭菌。NovaSterilis的过程是环保的，只使用二氧化碳和一种化学消毒剂，在这个过程中会分解成无害的化合物。第一阶段的工作确定了使用超临界二氧化碳(ScCO2)灭菌技术的最佳条件，该技术对按照ISO指南灭菌的SAL6缝合线的机械性能和细胞毒性没有不利影响。因此，第一阶段使我们能够展示超临界二氧化碳作为一种克服目前用于缝合的灭菌选择的限制的方法的可行性。使用我们的超临界二氧化碳工艺的终端灭菌有可能为缝合制造商和分销商增加一步验证的终端灭菌工艺，同时降低与当前环氧乙烷灭菌工艺相关的成本和负担。NovaSterilis准备开始体内和体外第二阶段高级测试，以评估scCO2灭菌缝合材料的商业准备情况，为医疗器械行业提供一种毒性更低、更温和的替代当前灭菌技术的方法。该项目的牵头公司NovaSterilis将其由经验丰富的工程师、化学家和生物学家组成的团队配对，其中包括顾问 康奈尔大学的Chu教授，缝合线开发领域的公认专家，以及动物毒性和有效性测试、放大和保质期测试方面的其他专家。TE第一阶段的合作已被证明非常成功，合理的商业化下一步将在第二阶段完成。主要目标是通过体内和体外商业准备测试，确保使用NovaSterilis超临界二氧化碳技术消毒的缝合线的安全性和有效性。

DESCRIPTION (provided by applicant): Over the past several decades there has been relatively little innovation in the arena of medical device sterilization. Ethylene oxide (ETO) and gamma irradiation (¿ irradiation) are the only technologies commercially available for medical devices. In particular, synthetic polymeric medical devices are sterilized almost exclusively by ETO due to undesirable chemical degradation and/or mechanical changes caused by gamma-irradiation. Gamma-irradiation requires cobalt-60 and these facilities are generally housed in large industrial or research institutions that have high operating costs associated with this technology. Suture manufacturers have expressed interest in moving from this process due to the short- and long-term negative effects of residual ETO in sterilized products, the fact that it s a recognized carcinogen, and the precautionary measures needed to operate around the toxic and explosive nature of ETO. Recently the EPA and other government agencies have started to monitor ETO in response to personal and environmental issues. Thus, development of alternative sterilization processes that are capable of achieving validated sterility assurance levels of 10-6 (SAL6) - the benchmark for medical devices - without the use of dangerous ETO or damaging ¿-irradiation is of great importance. The current proposed effort aims to advance NovaSterilis' supercritical carbon dioxide (scCO2) sterilization technology and produce a viable method to sterilize suture materials while maintaining suture mechanical properties. The NovaSterilis process is environmentally friendly and uses only carbon dioxide and a chemical sterilant that breaks down into benign compounds during the process. The Phase I work has established the optimal conditions using supercritical carbon dioxide (scCO2) sterilization technology that have no adverse effects on the mechanical properties and no cytotoxicity of sutures sterilized to SAL6 under ISO guidelines. Thus, the Phase I has allowed us to show feasibility of supercritical carbon dioxide as a method of overcoming the current limitations on sterilization options currently used for sutures. Terminal sterilization using our supercritical carbon dioxide process has the potential to add a one-step validated terminal sterilization process to suture manufacturers and distributors while decreasing the costs and burdens associated with current ethylene oxide sterilization processes. NovaSterilis is ready to begin Phase II in vivo and in vitro advanced testing to assess commercial- readiness of scCO2-sterilized suture materials to provide the medical device industry with a less toxic and more gentle alternative to current sterilization technologies. NovaSterilis, the lead company for this project, will pair its team of experienced engineers, chemists and biologists, including consultant Prof. CC Chu of Cornell University, a recognized expert in the arena of suture development, with additional experts in animal toxicity and efficacy testing, scale-up and shelf-life testing. Te Phase I partnership has proven highly successful, and the logical next steps towards commercialization will be accomplished in the Phase II. The primary goal is to ensure the safety and efficacy of sutures sterilized using NovaSterilis supercritical carbon dioxide technology through in vivo and in vitro commercial-readiness testing.