Periodic Reporting for period 3 - ADAPTOS (ADAPTOS - Changing the way bone voids are treated)
Periodo di rendicontazione: 2021-11-01 al 2023-03-31
Bone is the second most common tissue transplant in the world coming right after blood transfusions. Due to the aging population in the western world as well as in Asia, the need for bone tissue in different surgical operations will be increased as the elderly people are more prone to bone fractures and their bone regeneration capability is weaker than with juveniles’. The standard method for bone transplantation is to harvest bone from patient itself and implant the graft where needed. In many operations and situations, the harvested amount of bone from the patient itself is insufficient and extra volume is needed to secure successful operational results. The synthetic bone substitute materials available today are hard and brittle ceramic materials or paste-like materials, both of which lack the operation flexibility the surgeons would need for reliable and successful operations. Thus, the golden standard has remained as the patients’ own bone grafts are intuitive to use and can be modified to fit any type of operation where bone is needed.
The restrictions of existing bone substitute materials can be overcome by combining the properties of different materials into a bone-like synthetic composite structure that can be manufactured in large scale without harmful chemicals and with reasonable price. The background of the technology is based on years of research dealing with new and advanced polymer and composite processing methods for bioresorbable and bioactive materials as well as collaboration with clinicians working in the surgical disciplines relating bone regeneration.
The ADAPTOS project has three main goals: scaled production capability for Adaptos® bone grafts, specific human clinical trials in highly profitable orthopaedic market segments and early activities to orthopaedic market entry.
The planned upscale of the production capability is based on developing the foaming process for the composite. We have collaborated with a leading supplier of ScCO2–processing systems and the first phase of the newly designed and upscaled ScCO2-reactor system has been setup to cleanroom environment and the process development has been successfully conducted with the new system, as there were differences between the original system and the new up-scalable system. After test runs and validating the process, a second phase upscale will then increase the production volumes to their targets.
The sales approval process today in the EU requires clinical evidence included before the CE-mark can be granted to the product. To gain the needed proof of safety and efficacy for the CE-mark, a multi-centre clinical study is conducted as part of this project. Approvals for clinical study from the national regulatory body have been granted during the project. As the global pandemic significantly affected the ability of European hospitals to conduct clinical studies in 2020-2021 the clinical study was replanned and rebuilt to focus on major hospitals in Finland.
The early influence of clinicians and the dissemination of the possibilities of technology and gained results are among the most important matters in early market entry preparations. We have flexibly searched for methods to engage surgeons and other possible influencing players in the field, to both receive feedback of the technology as well as gain early adapters and possible key-opinion leaders to our network. Methods for the early engagement today combine effective and easily accessible web-content as well as face-to-face influencing, now in the post-covid era.
The restrictions of existing bone substitute materials can be overcome by combining the properties of different materials into a bone-like synthetic composite structure that can be manufactured in large scale without harmful chemicals and with reasonable price. The background of the technology is based on years of research dealing with new and advanced polymer and composite processing methods for bioresorbable and bioactive materials as well as collaboration with clinicians working in the surgical disciplines relating bone regeneration.
The ADAPTOS project has three main goals: scaled production capability for Adaptos® bone grafts, specific human clinical trials in highly profitable orthopaedic market segments and early activities to orthopaedic market entry.
The planned upscale of the production capability is based on developing the foaming process for the composite. We have collaborated with a leading supplier of ScCO2–processing systems and the first phase of the newly designed and upscaled ScCO2-reactor system has been setup to cleanroom environment and the process development has been successfully conducted with the new system, as there were differences between the original system and the new up-scalable system. After test runs and validating the process, a second phase upscale will then increase the production volumes to their targets.
The sales approval process today in the EU requires clinical evidence included before the CE-mark can be granted to the product. To gain the needed proof of safety and efficacy for the CE-mark, a multi-centre clinical study is conducted as part of this project. Approvals for clinical study from the national regulatory body have been granted during the project. As the global pandemic significantly affected the ability of European hospitals to conduct clinical studies in 2020-2021 the clinical study was replanned and rebuilt to focus on major hospitals in Finland.
The early influence of clinicians and the dissemination of the possibilities of technology and gained results are among the most important matters in early market entry preparations. We have flexibly searched for methods to engage surgeons and other possible influencing players in the field, to both receive feedback of the technology as well as gain early adapters and possible key-opinion leaders to our network. Methods for the early engagement today combine effective and easily accessible web-content as well as face-to-face influencing, now in the post-covid era.
The focus in the third period has been in ramping up the new system and developing the processing parameters and the overall foaming process to yield porous structures suitable for the clinical study and further for final sales approval process. The process development with the new system needed the reinventing the process leading high pore formation as we noticed major differences between the effects of different parameters between the original old system and the up-scalable new reactor system. The work conducted so far and overcoming the challenges related to the foaming process has resulted in the ability to manufacture superior porous composites with the new system in larger quantities than before. After the process validation, i.e. mandatory process to successfully conduct before the clinical study, the products for the clinical study can be delivered to the collaborating hospitals.
In the third period all documentation mandatory for the clinical study was generated and the mandatory processes of first receiving the approval from the ethical committee and further from the national regulatory body (Fimea) were received. The start of the patient recruitment will start immediately after the process validation for the new foaming process and the first validated foam structures are ready.
The commercial team has been significantly changed during the last period and more focus has been put to the ability to engage surgeons by people more capable of the engagement and background in the field of medicine and implantable medical devices.
The patent application and all rights for the invention were transferred from Tampere University to the company and several patents were issued globally, including in USA and China.
In the third period all documentation mandatory for the clinical study was generated and the mandatory processes of first receiving the approval from the ethical committee and further from the national regulatory body (Fimea) were received. The start of the patient recruitment will start immediately after the process validation for the new foaming process and the first validated foam structures are ready.
The commercial team has been significantly changed during the last period and more focus has been put to the ability to engage surgeons by people more capable of the engagement and background in the field of medicine and implantable medical devices.
The patent application and all rights for the invention were transferred from Tampere University to the company and several patents were issued globally, including in USA and China.
This project initiates a fundamental change in bone surgery as it is resolving a missing part of existing operation techniques – the graft usability, ability to tailor a synthetic bone graft similar fashion than the natural bone graft. The material is part of a broader material technology platform, which possibilities, e.g. antimicrobial properties, are studied in the future.
From a scientific perspective the health-related effects of the forthcoming clinical trial will be prominent, while the lack of high-quality, randomized, controlled clinical trials essentially impairs the interpretation of the results and reliable decision making of the orthopaedic surgeons. By means of this study we will provide strong evidence of the performance, safety, and usability of the Adaptos and juxtapose it with one of the notable bone graft substitutes currently on the market.
Clinical study regulations for medical devices are under strong shifting towards pharmaceutical regulation and at the same time they are made mandatory to reach the sales approval. The expertise gained in this project about the conduction and network building of a multicentre clinical study gives the conductive team a strong market position as the process itself is very demanding. Also due to the extremely expensive process many of the potential competitors cannot enter the market, which gives the successful teams clearing the clinical study phase better market entry possibilities than before.
From a health economic perspective, the use of synthetic bone grafts can render cost-saving in patients, when it provides enhanced, less risky surgical operations, less painful healing process and avoids the use of autogenous (patient’s own) bone. Comparison of patients treated with AdaptosOrtho or without a bone graft filler will provide health economic evaluation for the AdaptosOrtho in OWHTO surgery, but more importantly, this study will gather information for the Adaptos bone graft substitutes in orthopaedic surgery in wider perspective.
From a scientific perspective the health-related effects of the forthcoming clinical trial will be prominent, while the lack of high-quality, randomized, controlled clinical trials essentially impairs the interpretation of the results and reliable decision making of the orthopaedic surgeons. By means of this study we will provide strong evidence of the performance, safety, and usability of the Adaptos and juxtapose it with one of the notable bone graft substitutes currently on the market.
Clinical study regulations for medical devices are under strong shifting towards pharmaceutical regulation and at the same time they are made mandatory to reach the sales approval. The expertise gained in this project about the conduction and network building of a multicentre clinical study gives the conductive team a strong market position as the process itself is very demanding. Also due to the extremely expensive process many of the potential competitors cannot enter the market, which gives the successful teams clearing the clinical study phase better market entry possibilities than before.
From a health economic perspective, the use of synthetic bone grafts can render cost-saving in patients, when it provides enhanced, less risky surgical operations, less painful healing process and avoids the use of autogenous (patient’s own) bone. Comparison of patients treated with AdaptosOrtho or without a bone graft filler will provide health economic evaluation for the AdaptosOrtho in OWHTO surgery, but more importantly, this study will gather information for the Adaptos bone graft substitutes in orthopaedic surgery in wider perspective.