Periodic Reporting for period 1 - PRISMA (PERISTALTIC MULTISTAGE MICRO-MECHANICAL PUMP FOR NEXT GENERATION DIABETES MANAGEMENT)
Reporting period: 2021-04-01 to 2022-09-30
Diabetes is a major global problem, directly responsible for more than 1.6 million deaths, and other 2.2 million due to high blood glucose levels. It is estimated that around 422 million people are affected by this disease globally, with an incidence of about 8.5% of the adult population.
This condition can be treated with a lifestyle change and life-long insulin administration, but the correct amount of insulin requested is patient-specific and has a highly dynamic evolution over time, due to various factors, such as the composition of meals, sleep cycles and physical activity. Although progress has been made in this area, the ultimate smart patches still have large dimensions and lack of precision, which discourages patients who need them most.
In particular, current micro-pumps in insulin smart patches are mechanical. Their large volume is the major constraints to reduction of the total size of these devices. In addition, they are not so reliable in insulin infusion, so that patients who are very sensitive to the drastic increase/decrease in blood glucose are discouraged in their use. Pumps are the most important but also energy-consuming part of the insulin smart patches, forcing patient to recharge the entire device after a maximum of three days.
The PRISMA project was aimed to develop a new single electrostrictor membrane, which acts as insulin micro-pump. This completely new approach to insulin infusion could enables the development of the first fully functional artificial pancreas. The Prisma solution provides ideal regulation of the blood glucose concentration overcoming the limitations of standard solutions such as pen-based technology, as well as of standard pumping patch systems.
This condition can be treated with a lifestyle change and life-long insulin administration, but the correct amount of insulin requested is patient-specific and has a highly dynamic evolution over time, due to various factors, such as the composition of meals, sleep cycles and physical activity. Although progress has been made in this area, the ultimate smart patches still have large dimensions and lack of precision, which discourages patients who need them most.
In particular, current micro-pumps in insulin smart patches are mechanical. Their large volume is the major constraints to reduction of the total size of these devices. In addition, they are not so reliable in insulin infusion, so that patients who are very sensitive to the drastic increase/decrease in blood glucose are discouraged in their use. Pumps are the most important but also energy-consuming part of the insulin smart patches, forcing patient to recharge the entire device after a maximum of three days.
The PRISMA project was aimed to develop a new single electrostrictor membrane, which acts as insulin micro-pump. This completely new approach to insulin infusion could enables the development of the first fully functional artificial pancreas. The Prisma solution provides ideal regulation of the blood glucose concentration overcoming the limitations of standard solutions such as pen-based technology, as well as of standard pumping patch systems.
Within the 18 months of the project, two WP were active in parallel: WP1 and WP2, respectively focused on business and technological feasibility validation.
Concerning WP1, the business feasibility study started with an analysis of the insulin delivery scenario, considering all the devices now available and different approaches to insulin infusion. Then, a list of stakeholders including patients, diabetologists and insulin delivery device manufacturers were selected and then contacted, following a user centred design approach. Starting from the information collected, it was possible to define two typical end-users’ customer journeys – discovering their pains and gains – and to map performances and limitations of current insulin delivery device, until to profile an ideal insulin pump. All the qualitative information gathered, along with what was found on competitors, were then translated into technical specifics for the R&D using the House of Quality analysis tool. Despite preliminary assumptions, the analysis revealed that current devices are very advanced for what concerns all the hardware components - especially patient’s data management software – but not so much in infusion performances. Regarding the intellectual property assessment, the PRISMA micro-pump was firstly analysed as project result using a specific Key Exploitable Result (KER) table. This result was then compared with all the pertinent IPs, with focus on tri-hormones closed-loop system, smart patch technology and algorithms regulating the drug administration. On the other hand, the preliminary Freedom to Operate (FTO) analysis carried out did not reveal any patent potentially in contrast with PRISMA technology.
A preliminary Health Technology Assessment (HTA) followed, analysing cost-effectiveness and cost-utility for patient and health systems deriving from an improvement in Continuous Subcutaneous Insulin Infusion (CSII), such as that promised by PRISMA micro-pump adoption. In this sense, both systematic reviews and on modelling-based results were considered.
The assessment confirmed the potentially key role of the pump’s performances, even in economic terms. A in depth market analysis was then carried out, collecting information on market share and trends of diabetes therapy’s market, listing also the most relevant insulin pump manufacturers and the specifics of their devices.
This paved the way to the definition of a Product development roadmap, in which development status is resumed and the best way to exploit the project result was suggested.
As for the WP2, the first task performed was gathering knowledge on insulin therapy and the products available. The goal was to identify the necessary figures of merit to define our device specifications. We investigated the insulin standard dosage and the bolus mechanism. Then we studied the feasibility of a three-hormone therapy, which quickly resulted in not being practicable. We compared several closed-loop systems already available for diabetes patients and identified the minimal technical requirements for our device. We evaluated the feasibility of microneedles patches as delivery vectors. The idea of a small-sized and painless injection device is attractive, but after interaction with suppliers, physicians and literature review discarded the idea. We came to know microneedles are not suitable for long contact with the skin and are considered unreliable for continued insulin administration. CeOx and Day One were in close contact during these tasks to share useful information. Once identified the minimum and market-ready specification of an insulin pump, we integrated the information with our electrostriction knowledge and designed a base model. Through simulation we evaluated the performances of our pump in terms of energy consumption and flow rate. As the results were not satisfying for a market-ready device, we performed a parametric study of the model to optimize the features of the pump. The performances achieved were above the requirements defined, so we proposed an optimized final model.
We assembled then two types of prototypes: a multi-membrane one, working on peristaltic mode, and a single membrane one. Both modes were tested in a real fluidic circuit, using an optical microscope to measure the flow rate. The peristaltic pump did not show pumping action, probably due to inconsistency in each membrane module. The single pump instead, achieved a satisfactory flow rate.
Concerning WP1, the business feasibility study started with an analysis of the insulin delivery scenario, considering all the devices now available and different approaches to insulin infusion. Then, a list of stakeholders including patients, diabetologists and insulin delivery device manufacturers were selected and then contacted, following a user centred design approach. Starting from the information collected, it was possible to define two typical end-users’ customer journeys – discovering their pains and gains – and to map performances and limitations of current insulin delivery device, until to profile an ideal insulin pump. All the qualitative information gathered, along with what was found on competitors, were then translated into technical specifics for the R&D using the House of Quality analysis tool. Despite preliminary assumptions, the analysis revealed that current devices are very advanced for what concerns all the hardware components - especially patient’s data management software – but not so much in infusion performances. Regarding the intellectual property assessment, the PRISMA micro-pump was firstly analysed as project result using a specific Key Exploitable Result (KER) table. This result was then compared with all the pertinent IPs, with focus on tri-hormones closed-loop system, smart patch technology and algorithms regulating the drug administration. On the other hand, the preliminary Freedom to Operate (FTO) analysis carried out did not reveal any patent potentially in contrast with PRISMA technology.
A preliminary Health Technology Assessment (HTA) followed, analysing cost-effectiveness and cost-utility for patient and health systems deriving from an improvement in Continuous Subcutaneous Insulin Infusion (CSII), such as that promised by PRISMA micro-pump adoption. In this sense, both systematic reviews and on modelling-based results were considered.
The assessment confirmed the potentially key role of the pump’s performances, even in economic terms. A in depth market analysis was then carried out, collecting information on market share and trends of diabetes therapy’s market, listing also the most relevant insulin pump manufacturers and the specifics of their devices.
This paved the way to the definition of a Product development roadmap, in which development status is resumed and the best way to exploit the project result was suggested.
As for the WP2, the first task performed was gathering knowledge on insulin therapy and the products available. The goal was to identify the necessary figures of merit to define our device specifications. We investigated the insulin standard dosage and the bolus mechanism. Then we studied the feasibility of a three-hormone therapy, which quickly resulted in not being practicable. We compared several closed-loop systems already available for diabetes patients and identified the minimal technical requirements for our device. We evaluated the feasibility of microneedles patches as delivery vectors. The idea of a small-sized and painless injection device is attractive, but after interaction with suppliers, physicians and literature review discarded the idea. We came to know microneedles are not suitable for long contact with the skin and are considered unreliable for continued insulin administration. CeOx and Day One were in close contact during these tasks to share useful information. Once identified the minimum and market-ready specification of an insulin pump, we integrated the information with our electrostriction knowledge and designed a base model. Through simulation we evaluated the performances of our pump in terms of energy consumption and flow rate. As the results were not satisfying for a market-ready device, we performed a parametric study of the model to optimize the features of the pump. The performances achieved were above the requirements defined, so we proposed an optimized final model.
We assembled then two types of prototypes: a multi-membrane one, working on peristaltic mode, and a single membrane one. Both modes were tested in a real fluidic circuit, using an optical microscope to measure the flow rate. The peristaltic pump did not show pumping action, probably due to inconsistency in each membrane module. The single pump instead, achieved a satisfactory flow rate.
In the DoA, the main impact was expected in the area of wearable medical devices for diabetics, with the introduction of a multi-hormone device made possible by the new PRISMA micro-Pump.
The studies carried out and the interactions with physicians and patients revealed that the incorporation of the PRISMA micro-pump into current wearable devices - now too heavy, energy-consuming, and inaccurate - could generate a significative impact in the diabetic device market. The interest expressed by the companies contacted and the results of the market analysis led to a possible new exploitation strategy in which to focus development on a new micropump - always coupled with similar ones for infusion of multiple hormones - that could be integrated into their existing devices.
Therefore, the best way to exploit the realised technology would be to become a micro-pump supplier for one of the existing companies. Since a similar project dedicated solely to the development of a micro-pump has already emerged from the original FET OPEN BioWings project, PRISMA's know-how could complement that already present in that FET Transition project.
The studies carried out and the interactions with physicians and patients revealed that the incorporation of the PRISMA micro-pump into current wearable devices - now too heavy, energy-consuming, and inaccurate - could generate a significative impact in the diabetic device market. The interest expressed by the companies contacted and the results of the market analysis led to a possible new exploitation strategy in which to focus development on a new micropump - always coupled with similar ones for infusion of multiple hormones - that could be integrated into their existing devices.
Therefore, the best way to exploit the realised technology would be to become a micro-pump supplier for one of the existing companies. Since a similar project dedicated solely to the development of a micro-pump has already emerged from the original FET OPEN BioWings project, PRISMA's know-how could complement that already present in that FET Transition project.