A bio-artificial liver machine that has already worked in pre-clinical trials is being redesigned so that all its patient-contact parts are single-use, sterile disposables ready for first-in-human testing. Liver failure kills thousands of people each year in the UK, and the only long-term treatment is transplantation. Donor organs are scarce. This machine—the UCL Bio-Artificial Liver—is designed to temporarily take over the liver’s functions, buying time for a patient’s own liver to regenerate or bridging them to a transplant. The current reusable chamber cannot be used in patients because it cannot be sterilised reliably. The team is now engineering a disposable biocartridge, a giving-set to connect the patient, and a cryocassette to store the liver-cell biomass. A purified hydrogel powder, produced under clean-room conditions, will support the cells. All components must meet CE-mark regulatory standards. If the disposable system passes in-vitro tests with human blood, the device can enter a first-in-man clinical trial. Success would give clinicians a commercially viable, off-the-shelf bridge therapy for acute liver failure, potentially reducing deaths on the transplant waiting list and easing pressure on the organ donation system.
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To bring our novel BioArtificial Liver machine (UCLBAL) to a first-in-man clinical trial we need to translate the "hardware-components" of our "clinical-scale UCLBAL" - already proven in pre-clinical trials - from reusable to single-use disposables. This requires regulatory compliant materials delivered from drawings-to-tools to sterile-packaged disposables suitable for use in patients. Whilst we have existing Solidworks engineering drawings of our reusable chamber, design changes are required to accommodate disposable materials, and limitations of tool design. This applies to chamber, giving-set providing the interface, and cryocassette, i.e. each aspect of the necessary disposable components. A work-station to hold the BAL will be designed with PPI and stakeholder involvement. Plan of investigation, deliverables and milestones WP1: Tools for manufacture of Biocartridge. (Europlaz, with UCL design and testing). Tool design and production will start with a prototype tool-set in soft-steel, with the first chamber prototype produced from those tools, enabling the "finishing" process (addition of connectors/tubing etc.) to be designed and tested, and temperature compatibilities of the different materials assessed. After any necessary modifications the final tool set will be produced out of hardened-steel, to provide fully testable disposable chambers for use in the laboratory, and subsequently clinical trials and mass production. WP2: Design and prototype CE-mark ready "giving-set". (Allmed, UCL). Use re-usable circuitry to model disposable for clinical use. WP3: BAL workstation design. (RGi). Clinician/Patient-centred design, Usability design to BS.EN.62366. Engineering/prototype design. Formative usability study. Prototype (P1&P2) production. WP4: Design semi-rigid/flexible cryopreservation container (UCL with Origen). The cryocasette design is based on our accumulated data for cooling and warming that leads to acceptable BAL biomass recovery. Work involves engineering solidworks drawings from our functional design, tools and prototype production, and biological testing. Milestone 1: design and implementation of tool manufacture leading to disposable biomass chamber, cryocassette and giving-set. WP5: Purify hydrogel powder needed to enable biomass production (University of Miskolc, Hungary: subcontractor; UCL). Hydrogel dry powder will be purified using our existing SOP in a clean-room environment (MHRA/EMA guidelines), suitable for production of material that will be terminally-sterilised prior to incorporation into the UCLBAL. Biomass prepared from this material will be compared, from the perspective of supporting cellular organoid production and appropriate metabolic viability, with current batches prepared according to same SOP outside a cleanroom environment, Milestone 2: Purified packaged hydrogel powder meeting regulatory requirements WP6: Demonstration of biomass production and effective interface with apheresis machine (UCL). With these tasks completed, demonstrate the disposable "package" supports biomass production (n=3), interfaces with apheresis machine, and functions for ~ 8h using human blood/plasma in-vitro, to rigorously test the robustness of the system. Milestone 3: disposable hardware that is fit for purpose meeting regulatory requirements and delivered as a sterile product for clinical use. WP7: Cost analyses, and commercialisation, R. Fagan-UCLB (IP) and commercial co-applicants). The cost-of-goods for disposables for the clinical UCLBAL will be established by commercial co-applicants. Our health economics modelling has provided confidence that the UCLBAL will meet NICE guidelines for a commercially viable new therapy; our existing commercialisation plan will be extended, and IP generation completed. WP8: Regulatory Development: D.F,TRO, and Kinesys Regulatory Consulting Following completion of WPs 1-6, the technical file will be produced for disposable components making up the med
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