Building a commercially scalable bionic pancreas for automated diabetes management

通过波士顿大学（BU）和马萨诸塞州总医院（MGH）之间长达10年的合作，我们已经建立了纯胰岛素和双激素 我们的仿生胰腺（BP）的配置，并在住院患者，门诊患者和1型糖尿病（T1 D）患者的真实家庭使用研究中进行了广泛的测试。我们还进行了初步临床研究，测试了2型糖尿病（T2 D）患者的BP仅胰岛素配置和慢性低血糖患者的BP仅胰高血糖素配置。在过去的3年里，我们已经建立和测试了一个独立的，完全集成的BP设备，我们称之为iLet，它将我们的微精密双输注泵与连续葡萄糖监测仪集成在一起，（可选择Dexcom或Senseonics）以及我们经过临床测试的数学控制算法套件，可根据连续探头葡萄糖数据自动确定和控制胰岛素和胰高血糖素剂量。iLet平台的开发工作于2014年在BU的Co-PI实验室开始，然后于2016年1月翻译为Beta Bionics。第三代iLet（Gen 3 iLet）的开发在2017年和2018年初在Beta Bionics进行。我们在MGH和斯坦福大学的临床合作伙伴将于2018年5月开始在T1 D成人家庭环境中测试Gen 3 iLet的临床试验。该快速通道应用程序的目标是将我们在Gen 3 iLet中积累的所有经验、技术和创新整合到高度可靠、易于维修和商业可扩展的Gen 4 iLet的设计和开发中，该产品旨在在美国和其他全球市场广泛分销。本项目第一阶段的目标是利用我们从Gen 3 iLet的临床前和临床研究中了解到的信息，以告知、定义和实施我们的商业可扩展Gen 4 iLet和iLet一次性用品的最终设计和使用要求，并构建第一个适用于向FDA提交上市前批准（PMA）申请所需的最终关键试验的临床就绪器械。第二阶段的目标是逐步提高制造和分销过程的自动化和可扩展性，使第四代iLet在商业上可行并广泛使用，以满足其所需服务的最大可能需求。将通过以下具体目标实现这些目标：（1）实现我们可商业扩展的Gen 4 iLet的最终设计和使用要求（及其相关一次性用品），将通过我们的Gen 3 iLet系统的临床研究获得的数据提供信息，然后构建Gen 4 iLet系统的第一个临床可用原型，并提交试验用器械豁免（IDE）向美国FDA申请Gen 4 iLet系统，以及（2）获取、安装和验证将我们的几个手动组装过程转换为完全或部分自动化过程的制造机器，通过不断改进和提高第四代iLet的生产工艺和技术，和iLet管理套件。

Through a 10-year collaboration between Boston University (BU) and the Massachusetts General Hospital (MGH), we have built insulin-only and bihormonal configurations of our bionic pancreas (BP) and extensively tested them in inpatient, outpatient, and real-world home-use studies in people with type 1 diabetes (T1D). We have also conducted preliminary clinical studies testing the insulin-only configuration of our BP in people with type 2 diabetes (T2D) and the glucagon-only configuration of our BP in people with chronic hypoglycemia. Over the past 3 years, we have built and tested progressive generations of a stand-alone, fully integrated, BP device, which we call the iLet, that integrates our micro-precision dual-infusion pump with a continuous glucose monitor (choice of either the Dexcom or Senseonics) and our clinically tested suite of mathematical control algorithms that autonomously determine and command insulin and glucagon doses based on continuous sensor glucose data. The development effort of the iLet platform began in the Co-PI's lab at BU in 2014 and was then translated to Beta Bionics in January 2016. Development of the third-generation iLet (the Gen 3 iLet) took place at Beta Bionics throughout 2017 and into early 2018. Our clinical partners at MGH and Stanford University will begin clinical trials testing the Gen 3 iLet in a home-use setting in adults with T1D in May 2018. The objective of this Fast Track application is to integrate all of the cumulative experience, technology, and innovation that we have assembled in the Gen 3 iLet, into the design and development of a highly reliable, easily serviceable, and commercially scalable, Gen 4 iLet, which is intended for broad distribution in the US and other worldwide markets. The objective of Phase I of this project is to leverage what we learn from the preclinical and clinical studies of the Gen 3 iLet to inform, define, and implement the final design and use requirements of our commercially scalable Gen 4 iLet and iLet disposables and to build the first clinical-ready devices suitable for the final pivotal trial required for a premarket approval (PMA) application to the FDA. The objective of Phase II is to progressively improve automation and scalability in the manufacturing and distribution processes that will make the Gen 4 iLet commercially viable and widely accessible to meet the largest possible demand it will need to serve. These objectives will be achieved with the following specific aims: (1) to implement the final design and use requirements of our commercially scalable Gen 4 iLet (and its associated disposables), which will be informed by data obtained from clinical studies of our Gen 3 iLet system, and then to build the first clinical-ready prototypes of the Gen 4 iLet system and submit the investigational device exemption (IDE) application to the US FDA for the Gen 4 iLet system, and (2) to acquire, install, and validate manufacturing machinery that will transition several of our manual assembly processes to fully or partially automated processes, thus optimizing the efficiency of our manufacturing operations by continuously improving and advancing the process and technology used in the production of the Gen 4 iLet and iLet administration set.