Periodic Reporting for period 5 - NORMOPERF (Normothermic Perfusion Device for Renal and Hepatic Preservation and Viability Assessment)
Reporting period: 2022-12-01 to 2023-08-31
Despite the global success of organ transplantation, this technique is being severely hampered by remarkable constraints. The foremost limitation is the lack of sufficient organs, which is known worldwide as the organ shortage crisis. Furthermore, the short preservation time complicates the logistics of the organ transport and gives rise to out-of-hours activity of the medical team and a non-optimal use of the operating rooms. Also, the lack of objective information about the viability of the organ makes that potentially viable organs are discarded. All these constraints also involve huge costs to healthcare systems.
These limitations are all related to static cold storage (SCS), which is traditionally used to preserve the organ. Instead, EBERS has developed an organ preservation technology based on normothermic perfusion, which is based on maintaining the normal metabolic and functional activity of the organ during the ex vivo preservation to avoid the limitations of SCS. Thanks to our technology, it is possible to transplant more organs, with better clinical outcome, in safer conditions, with simpler logistics and lower costs.
The specific goals of the project are:
- Technical: industrialization of the process for manufacturing the commercial version of the product at a large scale.
- Clinical validation
- Regulatory & Commercial: CE marking and start negotiations for commercialization with potential customers and distributors.
The project has finished successfully, having achieved the following goals:
- The fabrication of the product is fully industrialized and can take place at large scale.
- The product has been validated clinically in a pilot clinical study using human discarded kidneys. In addition, a second multi-center controlled clinical study has been started and is currently undergoing. The goal of the clinical studies of the project was to provide sufficient evidence on the safety, efficacy and performance of the device such as to gain regulatory approval in the EU, and this goal has been achieved, as explained below.
- Regulatory approval: the company currently operates an ISO 13485 quality management system, has obtained a license of the Spanish Minister of Health for its manufacturing facilities and, most importantly, has obtained the CE mark for the ARK Kidney medical device. Obtaining the CE mark is a major milestone for the company that exceeds the goals of the project.
- Commercialization: the company has already started selling the device for research applications and is currently negotiating the first sales for clinical use to several customers in the EU. Furthermore, the company has made substantial progress towards the construction of a distributor network in the EU.
These limitations are all related to static cold storage (SCS), which is traditionally used to preserve the organ. Instead, EBERS has developed an organ preservation technology based on normothermic perfusion, which is based on maintaining the normal metabolic and functional activity of the organ during the ex vivo preservation to avoid the limitations of SCS. Thanks to our technology, it is possible to transplant more organs, with better clinical outcome, in safer conditions, with simpler logistics and lower costs.
The specific goals of the project are:
- Technical: industrialization of the process for manufacturing the commercial version of the product at a large scale.
- Clinical validation
- Regulatory & Commercial: CE marking and start negotiations for commercialization with potential customers and distributors.
The project has finished successfully, having achieved the following goals:
- The fabrication of the product is fully industrialized and can take place at large scale.
- The product has been validated clinically in a pilot clinical study using human discarded kidneys. In addition, a second multi-center controlled clinical study has been started and is currently undergoing. The goal of the clinical studies of the project was to provide sufficient evidence on the safety, efficacy and performance of the device such as to gain regulatory approval in the EU, and this goal has been achieved, as explained below.
- Regulatory approval: the company currently operates an ISO 13485 quality management system, has obtained a license of the Spanish Minister of Health for its manufacturing facilities and, most importantly, has obtained the CE mark for the ARK Kidney medical device. Obtaining the CE mark is a major milestone for the company that exceeds the goals of the project.
- Commercialization: the company has already started selling the device for research applications and is currently negotiating the first sales for clinical use to several customers in the EU. Furthermore, the company has made substantial progress towards the construction of a distributor network in the EU.
From the beginning of the project, we have performed the following tasks:
- Redesign of the complete product to obtain a final commercial version.
- Industrialization of the manufacturing process of the complete product
- Implementation and certification of a quality management system based on the ISO 13485 standard. The system was first implanted according to the EU MDD and was later successfully updated according to the MDR.
- Management of the regulatory process in the EU: the CE mark of the new medical device under the new MDR regulation has been obtained in the course of the project, which exceeds the main regulatory goal of the project, which was just to submit the regulatory application.
- Management of the regulatory process in the US: a pre-submission request was submitted to FDA to obtain guidance about the expected regulatory path of the product in the US and receive feedback on the design of the clinical study of the project.
- Pilot clinical study with human discarded organs, which has allowed us to obtain evidence on the safety and performance of the device, critical to gain regulatory approval.
- (Re)-Design of a second clinical study. The design of the controlled study has been changed with regards to the proposal of the project for two reasons: (i) the unexpected requirement of the notified body of a clinical trial to obtain the CE mark and (ii) feedback received by FDA. Thus, instead of a randomized controlled trial we have decided to conduct a single-arm study (due to the lack of CE mark) with a historical control arm and a longer follow-up period (FDA requirements).
- Approval and start of recruitment of the second clinical study. The clinical study has already been approved by the Ethics’ Committee, the Spanish Agency of Drugs and Medical Devices (AEMPS) and the Spanish National Transplant Organization (ONT). Contracts have been signed with participant centers and recruitment is currently undergoing.
- Intellectual property: we currently have three families of patents with international extension.
- Dissemination of the new technology and the results obtained so far among the clinical community and stakeholders (exhibition in conferences, participation in scientific, medical and investing forums, signature of distribution agreements, etc.).
- First research customers have started using our device: clinical (e.g. Clínic Hospital in Barcelona or Royal Infirmary of Edinburgh) and industry (e.g. the UK/US company Ochre-Bio). We have recently expanded our list of research customers with US clinical research centers (Mt. Sinai Hospital in NY).
- Commercial agreements: we are currently negotiating with a German-Spanish consortium of two companies, both with worldwide sales operations, a potential agreement including the distribution of our product and potential further co-developments and investments.
- Public Procurement of Innovation (PPI) contract granted: the company, in cooperation with two subcontractors, was granted a 2.5M€ PPI contract by the Spanish funding agency CDTI for the development of a second generation of normothermic perfusion machines.
- Redesign of the complete product to obtain a final commercial version.
- Industrialization of the manufacturing process of the complete product
- Implementation and certification of a quality management system based on the ISO 13485 standard. The system was first implanted according to the EU MDD and was later successfully updated according to the MDR.
- Management of the regulatory process in the EU: the CE mark of the new medical device under the new MDR regulation has been obtained in the course of the project, which exceeds the main regulatory goal of the project, which was just to submit the regulatory application.
- Management of the regulatory process in the US: a pre-submission request was submitted to FDA to obtain guidance about the expected regulatory path of the product in the US and receive feedback on the design of the clinical study of the project.
- Pilot clinical study with human discarded organs, which has allowed us to obtain evidence on the safety and performance of the device, critical to gain regulatory approval.
- (Re)-Design of a second clinical study. The design of the controlled study has been changed with regards to the proposal of the project for two reasons: (i) the unexpected requirement of the notified body of a clinical trial to obtain the CE mark and (ii) feedback received by FDA. Thus, instead of a randomized controlled trial we have decided to conduct a single-arm study (due to the lack of CE mark) with a historical control arm and a longer follow-up period (FDA requirements).
- Approval and start of recruitment of the second clinical study. The clinical study has already been approved by the Ethics’ Committee, the Spanish Agency of Drugs and Medical Devices (AEMPS) and the Spanish National Transplant Organization (ONT). Contracts have been signed with participant centers and recruitment is currently undergoing.
- Intellectual property: we currently have three families of patents with international extension.
- Dissemination of the new technology and the results obtained so far among the clinical community and stakeholders (exhibition in conferences, participation in scientific, medical and investing forums, signature of distribution agreements, etc.).
- First research customers have started using our device: clinical (e.g. Clínic Hospital in Barcelona or Royal Infirmary of Edinburgh) and industry (e.g. the UK/US company Ochre-Bio). We have recently expanded our list of research customers with US clinical research centers (Mt. Sinai Hospital in NY).
- Commercial agreements: we are currently negotiating with a German-Spanish consortium of two companies, both with worldwide sales operations, a potential agreement including the distribution of our product and potential further co-developments and investments.
- Public Procurement of Innovation (PPI) contract granted: the company, in cooperation with two subcontractors, was granted a 2.5M€ PPI contract by the Spanish funding agency CDTI for the development of a second generation of normothermic perfusion machines.
Our organ preservation method improves the quality of the organ during the preservation and avoids the ischemic damage caused to the organ by SCS, enhancing the post-transplant clinical results. For this same reason, our technique is compatible with suboptimal organs, which allows increasing significantly the donor pool. Also, the preservation time can go beyond 24 h, which makes simpler the logistics of transplantation. Furthermore, it is possible to perform real-time measurements of the organ function and estimate its viability. In this way, our technology also becomes a useful clinical decision support system for surgeons. All these positive impacts on the health of patients and activity of transplant surgeons and hospitals will also have a direct impact on the costs of healthcare systems, as we estimate that the use of our device will provide to our clients net savings of 15-30k€ per transplant procedure.
At end of the project, we have obtained regulatory approval for the new medical device in the EU. From a financial perspective, the launch of this product will involve a huge step forward for the company, as it will be our first medical device product, it will give us access to a new market of huge size and we expect to multiply by x10 our revenues in 3-4 years.
At end of the project, we have obtained regulatory approval for the new medical device in the EU. From a financial perspective, the launch of this product will involve a huge step forward for the company, as it will be our first medical device product, it will give us access to a new market of huge size and we expect to multiply by x10 our revenues in 3-4 years.