Periodic Reporting for period 4 - ADAPTOS (ADAPTOS - Changing the way bone voids are treated)
Reporting period: 2023-04-01 to 2024-09-30
Bone is the second most common tissue transplant in the world coming right after blood transfusions. Due to the aging of our population, 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.
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 in preparations of orthopaedic market entry.
The upscaling 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 newly designed and upscaled ScCO2-reactor system has been setup to cleanroom environment and the process development and process validations have been successfully conducted with the new system, as there were differences between the original system and the new up-scalable system.
The sales approval process 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 engaged 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.
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 in preparations of orthopaedic market entry.
The upscaling 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 newly designed and upscaled ScCO2-reactor system has been setup to cleanroom environment and the process development and process validations have been successfully conducted with the new system, as there were differences between the original system and the new up-scalable system.
The sales approval process 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 engaged 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.
The focus in the fourth period has been in validating and ramping up the manufacturing processes to produce porous structures suitable for the clinical study and further for final sales approval process. The actions taken with the newly developed and up-scaled processing system enable production volumes that can serve the early market entry of the Adaptos®-technology.
The agreement processes were finalized during the fourth reporting period with the leading hospital in the clinical study and the patient recruitment and surgical procedures were started. New teams at other clinical study locations were trained after the initiation at the leading site, and a second site also started patient recruitment.
Main part of the quality and regulatory documentation was finalized for both EU and US markets during the fourth reporting period and a pre-submission was filed for the US Food and Drug Administration (FDA). The broadening of the early market segment entry strategy from initial EU markets to also US markets, based on the work conducted during the project, enables also possibly faster sales approval process as the pre-market notification (510k) requires preclinical studies instead of broad clinical studies.
The surgeon engagement has been significantly boosted by a collaboration contract between Biomendex and Mayo Clinic that are agreed to engage in collaborative clinical studies.
The project significantly boosted both the manufacturing as well the actions needed to gain the sales approval, not only for the EU-markets, but also for the US-markets.
The technology developed, validated and scaled-up during the project has seemingly impacted the surgeons already with early results. The advancements in the manufacturing, regulatory affairs as well as the clinical results have enabled to build up a foundation for the future clinical collaboration with major healthcare providers. Despite the hurdles in building the clinical study network, a strong foundation for impactful clinical study was established that has the potential to generate high-level clinical data for the benefit of clinicians as well as the patients. Through the results generated within this project the healthcare system can provide better and easier treatments for patient population that is significantly growing.
The agreement processes were finalized during the fourth reporting period with the leading hospital in the clinical study and the patient recruitment and surgical procedures were started. New teams at other clinical study locations were trained after the initiation at the leading site, and a second site also started patient recruitment.
Main part of the quality and regulatory documentation was finalized for both EU and US markets during the fourth reporting period and a pre-submission was filed for the US Food and Drug Administration (FDA). The broadening of the early market segment entry strategy from initial EU markets to also US markets, based on the work conducted during the project, enables also possibly faster sales approval process as the pre-market notification (510k) requires preclinical studies instead of broad clinical studies.
The surgeon engagement has been significantly boosted by a collaboration contract between Biomendex and Mayo Clinic that are agreed to engage in collaborative clinical studies.
The project significantly boosted both the manufacturing as well the actions needed to gain the sales approval, not only for the EU-markets, but also for the US-markets.
The technology developed, validated and scaled-up during the project has seemingly impacted the surgeons already with early results. The advancements in the manufacturing, regulatory affairs as well as the clinical results have enabled to build up a foundation for the future clinical collaboration with major healthcare providers. Despite the hurdles in building the clinical study network, a strong foundation for impactful clinical study was established that has the potential to generate high-level clinical data for the benefit of clinicians as well as the patients. Through the results generated within this project the healthcare system can provide better and easier treatments for patient population that is significantly growing.
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 clinical study initiated in the project will be prominent, as at the moment, the lack of high-quality and 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 Adaptos®Ortho or without a bone graft filler will provide health economic evaluation for the Adaptos®Ortho 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 clinical study initiated in the project will be prominent, as at the moment, the lack of high-quality and 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 Adaptos®Ortho or without a bone graft filler will provide health economic evaluation for the Adaptos®Ortho in OWHTO surgery, but more importantly, this study will gather information for the Adaptos® bone graft substitutes in orthopaedic surgery in wider perspective.