Skip to main content

Normothermic Perfusion Device for Renal and Hepatic Preservation and Viability Assessment

Periodic Reporting for period 3 - NORMOPERF (Normothermic Perfusion Device for Renal and Hepatic Preservation and Viability Assessment)

Reporting period: 2020-12-01 to 2021-11-30

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. Official estimations of the WHO confirm that only 10% of the global organ needs for transplant are being covered nowadays. 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.
From the beginning of the project, we have performed the following tasks:
- Redesign of the complete product to obtain a final commercial version that can be manufactured at a large scale and is aesthetic and usable.
- Industrialization of the manufacturing process of the complete product, including the fabrication of molds, selection of critical suppliers, the validation of critical manufacturing processes, etc.
- 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 certified by the notified body BSI. This certificate has been recently transferred successfully to a different notified body (IMQ) and has been successfully updated according to the MDR regulation.
- Management of the regulatory process in the EU: all necessary assays required by MDD were carried out successfully and the technical file was audited by BSI. Unfortunately, the outcome was negative, as BSI unexpectedly decided to require a clinical study in order to grant the CE mark, which contradicts the previous opinion given by BSI. Thus, while the required clinical trial is executed, the technical file has been adapted to the new MDR and some extra assays required by MDR have been carried out. In addition, we have submitted the new MDR technical file to our current notified body (IMQ) and we expect to receive first feedback within the next weeks.
- 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 with human discarded organs, which has served as a test before the actual clinical study.
- (Re)-Design of the clinical study. The design of the 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 the clinical study. The clinical study has already been approved by the Ethics’ Committee and the Spanish Agency of Drugs and Medical Devices (AEMPS). Contracts have been signed with participant centers and the study has officially started.
- Intellectual property: a European patent has been granted and has been validated in several EU countries. In addition, a second patent has been filed in Spain and is currently being extended internationally.
- 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. Among first customers we have both clinical researchers (e.g. Clínic Hospital in Barcelona or Royal Infirmary of Edinburgh) and industry (e.g. the UK/US company Ochre-Bio). We expect to expand our list of research customers in 2022 with US clinical research centers (e.g. Mt. Sinai Hospital in NY) and more private companies.
- Commercial agreements: we are currently negotiating with a couple of US companies with worldwide sales operations a potential agreement including the distribution of our product and potential further co-developments.
- Public Procurement of Innovation (PPI) contract granted: the company, in cooperation with two subcontractors, has been recently granted a 2.5M€ PPI contract by the Spanish funding agency CDTI. This non-dilutive funding will allow EBERS to develop and validate a second generation of the normothermic perfusion machines.
We remark here that the unexpected decision of the notified body concerning the requirement of a clinical study to obtain the CE mark and the COVID pandemic introduced a significant delay in the project and an amendment was asked for to the European Commission, which was granted.
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 -older or asystolic donors, donors with previous comorbidities, etc., which allows increasing significantly the donor pool. Also, the preservation time can go beyond 24 h, which makes simpler the logistics of transplantation. Furthermore, since the organ is working normally while it is connected to our device, it is possible to perform real-time measurements of its function and quality and, thanks to the use of proprietary artificial intelligence algorithms developed by EBERS, 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.
By end of the project, we expect to have finished the clinical validation study with satisfactory results that support the product launch. From a financial perspective, the launch of this product to the market 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.
Logo of the NORMOPERF project
Front view of the final version of the device (open)
Front view of the final version of the device (closed)