Periodic Reporting for period 1 - Para-T System (The Para-T System A quick blood group device to match in situ the donor bag and the receptor arm during a blood transfusion, avoiding major incompatible errors.)
Reporting period: 2018-06-01 to 2018-11-30
Summary of the context and overall objectives of the project
One in four people will need a blood transfusion at some point in his/her live. Blood transfusion save patients life and prevent the complications of severe blood loss in surgeries and cancer patients. In most cases, blood transfusion is safe, preventing negative consequences for patients; however, severe adverse events occasionally occur. Most severe events in blood transfusion come from human errors, when blood transfused do not match the patient´s ABO blood type. These errors affect the recipient's immune system destroying the red blood cells from donor, with severe and harmful consequences even the death of patient. This is known as an acute haemolytic reaction due to ABO incompatible red blood cell (RBC) transfusion. and although unusual (1 in 10.000 RBC transfusions) and avoidable, it is the most frequent cause of death derived from transfusions.
The Para-T System is defined as a medical device to perform a direct, quick and permanent ABO group identification in a bag containing whole blood or red blood cells and/or in the catheter inserted in the vein of a patient, to identify the patient´s ABO group and to prevent incompatible ABO transfusions between the transfusion bag and the recipient.
The Para-T System is based in disposable transfusion set, comprising two parts: the bag device and the patient device and a reading and control unit. By a simple visual inspection or using a reading QR device (PDA that command a solenoid valve), the blood group (A, B, AB or O) of the bag and the blood group of the patient can be permanently compared before transfusion, preventing incompatible ABO transfusions (visually in the cheapest solution or automatically in the more complex solution). The market of the Para-T System can be classified into clinical laboratories, blood banks, hospitals, blood transfusion services and all public organization which help to save lives in low incomes countries and during wars, conflicts and emergencies. It could help to save many lives and is very cost effective.
The following specific goals are pursuit in the Para-T project phase II:
• Product refinement of the biochemical process to identify the blood ABO group using reaction chambers with solid/gel anti-reagents.
• Manufacturing of advance plastic cassettes including the reaction chambers and the readable chambers with a QR code impressed to identify the ABO group and the patient’s identification data.
• Fully adapt our current near-to-industrialized system for industrial production, for which we will work with the technological center AIMPLAS, to manufacture the complete Para-T medical device. The Para-T system compares the ABO group in the donor bag containing Whole Blood or Red Blood Cells (RBCs) and the ABO group in the catheter inserted in the vein of a patient, preventing incompatible transfusions between both. PROPOSIT and AIMPLAS will work together in the design of the pre-industrial production line addressed to facilitate the parallel negotiations with the selected manufacturer.
• Development of the computing program (APP-based) to check compatibility between bag and patient’s cassettes and interconnection with all the additional medical components (magnetic valve release device coupled, luer connections, anti-return valves, etc) to allow a robust and reliable identification system.
• Performing material tests to find the best plastics and anti-reagents for a feasible ABO group checking and later, lab and pilot massive trials with whole blood and RBCs to create evidence of the effectiveness of the Para-T system, improving recognition for the new product to reduce the morbidity and mortality rates of blood recipient patients. Clinical trials with real patients are not necessary to get certification (as there is not interaction between reactants and main blood line due to the anti-return valves) although real patients will provide accredited consent to use their blood for research purposes. The Centre for Hemotherapy and Hemodonation of the Castilla and Leon region has agreed to perform almost 9.000 trials around Para-T with their patients’ blood. The results of these trials will be published in high impact scientific journals, giving a high visibility and prestige to the PROPOSIT Para-T solution among physicians.
• Extend the on-going European Patent to selected countries (10) where the number of donations represent the 83% of the whole donations in Europe. Establish distribution agreements inside Europe after the freedom to operate analysis.
• Overcome the certification barrier. We will take the actions needed to prepare the CE marking with the Medicament Spanish Agency (AEMPS) at the end of the project.
• Accelerate the international expansion by disseminating the results among the doctors, pharma companies, Hematology educators, Hospitals, Transfusion centres, sectorial associations, etc. PROPOSIT is in touch with some key stakeholder showing great interest. Among others, we must highlight the interest of the Minister of Health of Argentina (Prof. Dr. Jorge Daniel Lemus), the Spanish Federation of Blood Donors, the world leading transfusion companies, Terumo and Technoflex, the Richi Foundation of Boston (strong health accelerator), the Spanish Military Transfusion Centre and several hospitals (please check letters of support in annex section 4-5).
• After this stage, private investment will be negotiated (Phase 3), additionally to the investment round we are in process to carry out in the frame of the entrepreneur program called Richi Social Entrepreneur launched by the Richi Foundation (summer 2018). Please check annex in section 4-5.
The Para-T System is defined as a medical device to perform a direct, quick and permanent ABO group identification in a bag containing whole blood or red blood cells and/or in the catheter inserted in the vein of a patient, to identify the patient´s ABO group and to prevent incompatible ABO transfusions between the transfusion bag and the recipient.
The Para-T System is based in disposable transfusion set, comprising two parts: the bag device and the patient device and a reading and control unit. By a simple visual inspection or using a reading QR device (PDA that command a solenoid valve), the blood group (A, B, AB or O) of the bag and the blood group of the patient can be permanently compared before transfusion, preventing incompatible ABO transfusions (visually in the cheapest solution or automatically in the more complex solution). The market of the Para-T System can be classified into clinical laboratories, blood banks, hospitals, blood transfusion services and all public organization which help to save lives in low incomes countries and during wars, conflicts and emergencies. It could help to save many lives and is very cost effective.
The following specific goals are pursuit in the Para-T project phase II:
• Product refinement of the biochemical process to identify the blood ABO group using reaction chambers with solid/gel anti-reagents.
• Manufacturing of advance plastic cassettes including the reaction chambers and the readable chambers with a QR code impressed to identify the ABO group and the patient’s identification data.
• Fully adapt our current near-to-industrialized system for industrial production, for which we will work with the technological center AIMPLAS, to manufacture the complete Para-T medical device. The Para-T system compares the ABO group in the donor bag containing Whole Blood or Red Blood Cells (RBCs) and the ABO group in the catheter inserted in the vein of a patient, preventing incompatible transfusions between both. PROPOSIT and AIMPLAS will work together in the design of the pre-industrial production line addressed to facilitate the parallel negotiations with the selected manufacturer.
• Development of the computing program (APP-based) to check compatibility between bag and patient’s cassettes and interconnection with all the additional medical components (magnetic valve release device coupled, luer connections, anti-return valves, etc) to allow a robust and reliable identification system.
• Performing material tests to find the best plastics and anti-reagents for a feasible ABO group checking and later, lab and pilot massive trials with whole blood and RBCs to create evidence of the effectiveness of the Para-T system, improving recognition for the new product to reduce the morbidity and mortality rates of blood recipient patients. Clinical trials with real patients are not necessary to get certification (as there is not interaction between reactants and main blood line due to the anti-return valves) although real patients will provide accredited consent to use their blood for research purposes. The Centre for Hemotherapy and Hemodonation of the Castilla and Leon region has agreed to perform almost 9.000 trials around Para-T with their patients’ blood. The results of these trials will be published in high impact scientific journals, giving a high visibility and prestige to the PROPOSIT Para-T solution among physicians.
• Extend the on-going European Patent to selected countries (10) where the number of donations represent the 83% of the whole donations in Europe. Establish distribution agreements inside Europe after the freedom to operate analysis.
• Overcome the certification barrier. We will take the actions needed to prepare the CE marking with the Medicament Spanish Agency (AEMPS) at the end of the project.
• Accelerate the international expansion by disseminating the results among the doctors, pharma companies, Hematology educators, Hospitals, Transfusion centres, sectorial associations, etc. PROPOSIT is in touch with some key stakeholder showing great interest. Among others, we must highlight the interest of the Minister of Health of Argentina (Prof. Dr. Jorge Daniel Lemus), the Spanish Federation of Blood Donors, the world leading transfusion companies, Terumo and Technoflex, the Richi Foundation of Boston (strong health accelerator), the Spanish Military Transfusion Centre and several hospitals (please check letters of support in annex section 4-5).
• After this stage, private investment will be negotiated (Phase 3), additionally to the investment round we are in process to carry out in the frame of the entrepreneur program called Richi Social Entrepreneur launched by the Richi Foundation (summer 2018). Please check annex in section 4-5.
Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far
The feasibility study addressed in phase have included the following actions:
1. Validate the technology and refine the product features according to the market study. Although several explorations have already been made in the market and the preliminary product has been presented to several stakeholders, with a positive feedback (please check annex), it is necessary to clarify the most interesting applications for the device and on that basis, determine its final characteristics.
2. Implement the Market Study. Asking the potential clients (big Pharma´s, blood donation centres and/or hospital transfusion units) the degree of interest in a product like this. These customers must be polled, checking also opinion of regulatory bodies and public administrations. Finally, the Health Organizations involved in developing countries are relevant where the Para-T system could be a simple, cheap and quick method for the ABO blood group determination. Potential competitors, sales channels, manufacturing requirements, suppliers, etc. must be checked and identified.
3. Define the business model, risks and the industrialization pathway. All large pharmaceutical companies interviewed to date (please check letters of interest in annexes), perceive the product as an upgrade to their current transfusion safety systems, providing an added value to differentiate them from competitors, and consequently, able to increase their market share. However, it is paramount to analyse also the business model from the point of view of PRoPosit and to that end, it is needed to identify where is placed within the value chain where the most added value is reached. The industrialization pathway for the developed product and all the associated risks arising from the market uptake of the new product will be also revised (pricing, costs, who manufacture, alliances, risks, etc).
4. Stablish a clear strategy for the IPR, certification process and freedom to operate. At the time this proposal is written, the Spanish patent is finalized and approved officially shortly. The European patent is ongoing with also good expectations. However, the market study must provide the extra protection needs and the freedom to operate in those areas determined by the market study. The business model finally selected will also affect the protection needs. Hence, the feasibility study will help to identify this IPR strategy in collaboration with the current patent office contracted. The certification process will be also revised and included in such strategy.
Main results have been:
The Para-T system has been very well received in the market. It is considered as a great idea that can reduce the number of fatal mortality and/or high morbidity events at low cost and very easy to implement. The Spanish patent has been yet taken and the European is on the right track. Technically, the first prototypes have been 90% successful and it is intuited that they will be able to be developed with the necessary quality in phase II if acceded. As a result of the surveys carried out by experts, a strategic alliance with one of the global pharmaceutical companies is necessary since several tier 1 suppliers are required as partners to close the complete supply chain. It is necessary to leave the blood bags prepared to attach the cassettes (also manufactured at the plastics’ converter) from the very beginning at the premises of the tier 1 supplier. Then introduce the reagents at PRoPosit factory and then send back to the blood bag manufacturer when finished the operation. Then the final product could be commercialized by the tier 1 distributor (in case of a white brand) or using PRoPosit own distributor (in case of its own brand). That supposes to manage a large number of suppliers that requires the push of large pharma if possible. For this reason, many interviews with these companies are in place during the preparation process.
1. Validate the technology and refine the product features according to the market study. Although several explorations have already been made in the market and the preliminary product has been presented to several stakeholders, with a positive feedback (please check annex), it is necessary to clarify the most interesting applications for the device and on that basis, determine its final characteristics.
2. Implement the Market Study. Asking the potential clients (big Pharma´s, blood donation centres and/or hospital transfusion units) the degree of interest in a product like this. These customers must be polled, checking also opinion of regulatory bodies and public administrations. Finally, the Health Organizations involved in developing countries are relevant where the Para-T system could be a simple, cheap and quick method for the ABO blood group determination. Potential competitors, sales channels, manufacturing requirements, suppliers, etc. must be checked and identified.
3. Define the business model, risks and the industrialization pathway. All large pharmaceutical companies interviewed to date (please check letters of interest in annexes), perceive the product as an upgrade to their current transfusion safety systems, providing an added value to differentiate them from competitors, and consequently, able to increase their market share. However, it is paramount to analyse also the business model from the point of view of PRoPosit and to that end, it is needed to identify where is placed within the value chain where the most added value is reached. The industrialization pathway for the developed product and all the associated risks arising from the market uptake of the new product will be also revised (pricing, costs, who manufacture, alliances, risks, etc).
4. Stablish a clear strategy for the IPR, certification process and freedom to operate. At the time this proposal is written, the Spanish patent is finalized and approved officially shortly. The European patent is ongoing with also good expectations. However, the market study must provide the extra protection needs and the freedom to operate in those areas determined by the market study. The business model finally selected will also affect the protection needs. Hence, the feasibility study will help to identify this IPR strategy in collaboration with the current patent office contracted. The certification process will be also revised and included in such strategy.
Main results have been:
The Para-T system has been very well received in the market. It is considered as a great idea that can reduce the number of fatal mortality and/or high morbidity events at low cost and very easy to implement. The Spanish patent has been yet taken and the European is on the right track. Technically, the first prototypes have been 90% successful and it is intuited that they will be able to be developed with the necessary quality in phase II if acceded. As a result of the surveys carried out by experts, a strategic alliance with one of the global pharmaceutical companies is necessary since several tier 1 suppliers are required as partners to close the complete supply chain. It is necessary to leave the blood bags prepared to attach the cassettes (also manufactured at the plastics’ converter) from the very beginning at the premises of the tier 1 supplier. Then introduce the reagents at PRoPosit factory and then send back to the blood bag manufacturer when finished the operation. Then the final product could be commercialized by the tier 1 distributor (in case of a white brand) or using PRoPosit own distributor (in case of its own brand). That supposes to manage a large number of suppliers that requires the push of large pharma if possible. For this reason, many interviews with these companies are in place during the preparation process.
Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)
Para-T System is disruptive because for the first time the identification of the ABO group is attached to the blood bag (as a constitutive element) and to the vein of the patient, providing a fast-visual identification of the major ABO groups and allowing easy matching. This system eliminates 4 typing confirmatory ABO checks from donor to patient resulting on high cost savings at hospital level and to the health system. In the complex solution, when reading the cassettes chambers by a PDA software system and connecting the output results to a solenoid valve, the complete Para-T System prevents the infusion of inappropriate blood to any recipient automatically without requiring special skills from bedside nurses. The novelty is also connected with the special anti-reagent chambers with a biocompatible and ommiophobic polycarbonate and ABO reagents, applied by PRoPosit Bio, which provide a quick and feasible ABO group identification. This novelty has been confirmed by the Spanish Patent 201630992 (also, European patent in process). The number of institutions and organizations attracted by the idea, opens great business opportunities as proponents believe that this simple system could be approved by the World Health Organization as a standard for all RCBs bags sold worldwide.
Economic impact for Hospitals and the Health Service
In the whole donation process , the blood is typed 7 times from donor to patient. However, 4 of the test are “confirmatory”, only to verify that there isn’t an error of identification with pernicious consequences for the patient. Each of these four identification processes consume on average 5 minutes of staff plus the material used. As a way of example, the Puerta de Hierro Hospital carry out somehow 15.000 transfusions per year. That means; (4*5 min*15.000 /60) = 5.000 h of staff dedication unnecessary if we had used Para-T. This is around 2,8 persons /year with an average cost of 22.000 € each. In addition, the blood typing kit cost for a hospital rounds 0,1€/test, representing additional 6.000 €/year (assuming 15.000 donations per year). The Para-T system will cost as well around 0.7€/unit (simple version) and 1.4 €/unit (complex solution). In our calculations for a business case of 3.750 patients with an average of 2,5 bags per patient, the total cost of bed side tests should be 11,598 € (unefficient to detect errors), if we use an electronics quality management system, the cost should be 49,098 € whilst using Para-T could be 20,813 € (basic system) and 30,563 € (complex system), comparable or even surpassing the electronic management system in terms of errors detection but 38% cheaper.
As is proven every year, despite current transfusion safety systems, errors continue to occur with dramatic consequences for the sick patients and legal consequences for the doctors or nurses involved. A patient affected by an error of the ABO group with high morbidity is generally admitted between one and two days in the intensive care unit, with the extra cost involved (approximately 1,500 € per day of hospitalization). Medical personnel may also be accused of malpractice which generates additional working pressure since they can go to jail. In low-incomes countries, the Para-T (simple solution) could be a really cheap option to prevent ABO identification errors.
Economic impact for Hospitals and the Health Service
In the whole donation process , the blood is typed 7 times from donor to patient. However, 4 of the test are “confirmatory”, only to verify that there isn’t an error of identification with pernicious consequences for the patient. Each of these four identification processes consume on average 5 minutes of staff plus the material used. As a way of example, the Puerta de Hierro Hospital carry out somehow 15.000 transfusions per year. That means; (4*5 min*15.000 /60) = 5.000 h of staff dedication unnecessary if we had used Para-T. This is around 2,8 persons /year with an average cost of 22.000 € each. In addition, the blood typing kit cost for a hospital rounds 0,1€/test, representing additional 6.000 €/year (assuming 15.000 donations per year). The Para-T system will cost as well around 0.7€/unit (simple version) and 1.4 €/unit (complex solution). In our calculations for a business case of 3.750 patients with an average of 2,5 bags per patient, the total cost of bed side tests should be 11,598 € (unefficient to detect errors), if we use an electronics quality management system, the cost should be 49,098 € whilst using Para-T could be 20,813 € (basic system) and 30,563 € (complex system), comparable or even surpassing the electronic management system in terms of errors detection but 38% cheaper.
As is proven every year, despite current transfusion safety systems, errors continue to occur with dramatic consequences for the sick patients and legal consequences for the doctors or nurses involved. A patient affected by an error of the ABO group with high morbidity is generally admitted between one and two days in the intensive care unit, with the extra cost involved (approximately 1,500 € per day of hospitalization). Medical personnel may also be accused of malpractice which generates additional working pressure since they can go to jail. In low-incomes countries, the Para-T (simple solution) could be a really cheap option to prevent ABO identification errors.