AdvanCell Isotope Generator

The challenge for the next-generation AdvanCell Generator was to enhance the capabilities of its predecessor by significantly increasing the number of units that could fit into a defined manufacturing environment. This was achieved by reducing the system’s physical footprint through optimised internal components and configuration, and integrating with a new external third-party fluidics system for processing. It required a modular, stackable system design to fit within standard lead-lined radioisotopic production cabinets. The generator needed to be mechanically operated, use materials that prevent trace metal contamination, and maintain the aesthetic and functional design language of the earlier model while improving usability and access. These factors were crucial to advance the generator’s operational efficiency and production capacity, meeting the growing demand for reliable and scalable targeted alpha therapeutics.

The AdvanCell Generator was engineered to upscale clinical dose production while minimising its footprint to fit standard hot-cell cabinets. This development responded to the critical need for a compact yet powerful device capable of delivering commercial scale output. Key engineering challenges involved integrating the system with an external fluidics unit to ensure GMP compliance and designing robust internal shielding with a tungsten container for safety. The design journey included configuring accessible modules for easy maintenance, and addressing the need for continuous operation with a refuelling schedule every 12-18 months, allowing the generator to meet the critical demand for increased, reliable production of lead-212 for targeted alpha therapeutics.

The AdvanCell Generator substantially increases production from a standard footprint, significantly enhancing the availability of targeted alpha therapies for cancer. This advancement boosts local production capabilities, substantially mitigating challenges linked to the short half-life of Lead-212 and its transportation, thus reducing environmental impact. By enabling scalable and redundant production of the active pharmaceutical ingredient (API) Lead-212 radiopharmaceutical under Good Manufacturing Practice (GMP) standards, the generator broadens access to scarce but crucial treatments. This scalable production meets high commercial demand and improves societal health outcomes by providing timely access to novel targeted alpha therapies for patients who need it most.

Mechanical Design: The generator operates pneumatically, minimising electronic dependencies which enhances reliability and reduces potential electronic failure points. The unique internal configuration allows the system to switch effectively from isotope collection cycle to wash cycle, whilst maintaining a sealed environment for the safe handling of radioactive materials and fluids including hydrochloric acid. Material Selection: Emphasis on non-metal components where possible to prevent trace metal contamination, critical for maintaining the purity of the radiopharmaceuticals produced. Ease of Servicing: Designed with front and side access panels that simplify the process of servicing and component replacement, ensuring that maintenance can be carried out quickly and safely. Advanced Safety Features: Includes a comprehensive shielding strategy using tungsten and additional robust materials to protect operators from radiation exposure during production. Multiple interlock and failure mode sensors ensure process and operator safety. Modular Configuration: Each module can be independently maintained or replaced, allowing for continued operation of the system even during servicing of individual components. Integration with Existing Systems: Designed to seamlessly integrate with third-party systems like the MultiSyn, enhancing its functionality and allowing for flexible adaptation to different production environments. Automated Processes: Features an automated sequence for isotope harvesting and processing, reducing operator workload and minimising the risk of human error. International Recognition: Targeted alpha therapies are among the most promising in oncology and reliable and scalable alpha emitting isotope supply is one of the biggest challenges. This generator, designed in Australia, is and will be recognised globally for its impact on the fight against cancer.