Medical Devices
Technical Challenges in Developing an Artificial Pancreas System
Recreating the precise and dynamic glucose-regulating function of a healthy pancreas is a challenging task. This task is further complicated by the numerous behavioral and biologic factors that impact diabetes management, and by the current limitations of the devices that are components of the artificial pancreas.
Current FDA approved or cleared diabetes management devices used as intended have dramatically changed the quality of life for people with type 1 diabetes. While the FDA has determined them safe and effective in their individual uses, these devices have not yet been proven safe and effective working together in a closed-loop system.
Researchers have made significant progress towards combining these devices into a more dynamic system and the FDA will continue to prioritize the development of an artificial pancreas system.
The FDA's two Draft Guidance for Industry and the Food and Drug Administration Staff: The Content of Investigational Device Exemption (IDE) and Premarket Approval (PMA) Applications for Low Glucose Suspend (LGS) Device Systems and Content of Investigational Device Exemption (IDE) and Premarket Approval (PMA) Applications for Artificial Pancreas Device Systems Draft Guidance will help manufacturers and investigators develop and gain approval for low glucose suspend and artificial pancreas systems.
But, for future artificial pancreas systems that could provide more accurate glucose control, more research on the components that may make up these systems is necessary. Here are some examples of areas where more research is needed:
Glucose Sensors
Continuous glucose monitoring systems (CGMs) incorporate sensors that measure glucose levels and change in glucose levels in the fluid around the cells (interstitial fluid). These levels may differ from the levels of glucose circulating in the blood.
CGM sensors often build up organic matter on their surfaces (biofouling) or in close proximity (fibrosis) once they are inserted under the skin. Biofouling or fibrosis could potentially impact the effectiveness and implantation duration of the sensors, which may lead to inaccurate readings or cause sensors to stop working.
More research and advances in sensor technology will help continuous glucose monitoring systems more accurately and quickly measure blood glucose levels and resist biofouling and fibrosis.
Blood Glucose Devices
Currently, to get the most accurate estimates of blood glucose possible from a CGM, the patient needs to periodically calibrate the CGM using a blood glucose measurement from a blood glucose device (BGD); therefore, the BGD still plays a critical role in the proper management of patients with an artificial pancreas system. However, over time, we anticipate that improved CGM performance may obviate the need for periodic blood glucose checks with a BGD.
Infusion Pumps
The FDA has identified problems with the mechanical components and software of many insulin infusion pumps. These problems have led to improper insulin dosing and compromised patient safety.
These known problems with infusion pump software present challenges to creating the computer programs that connect insulin infusion pumps and CGMs in an artificial pancreas. The FDA has taken steps to bring safer infusion pumps to market, but more research and innovation would improve the overall safety and effectiveness of the pumps, and thus of any artificial pancreas system.
Insulin
The insulin currently used in artificial pancreas systems takes hours to completely absorb, and absorption rates can vary among patients as well as for the same patient throughout the day. Creating a control algorithm that allows the CGM to take both these factors into account is difficult. Thus the development of faster-acting insulin would compress the variability of bolus insulin absorption and improve the effectiveness of artificial pancreas systems by enabling them to calculate more effective insulin doses.
Glucagon
There is no FDA-approved glucagon formulation that can be used in an artificial pancreas system outside of a research study. There is a need for a glucagon formulation that is stable over several days and can be delivered by an infusion pump.
Control Algorithms
Further development of control algorithms could lead to safer, more reliable and robust artificial pancreas systems. For instance, adding redundancies in the control algorithm can help the system check itself and prevent dosing errors. In the absence of a fast-acting insulin, a control algorithm may need to address the variability of insulin absorption. In addition, algorithms that can allow for variations between patients by incorporating additional physiologic measures, such as physical activity, could lead to more precise control of blood glucose.
