Ready-to-Use formulation of Sonazoid for contrast enhanced ultrasound imaging and therapy

Sonazoid is a world leading contrast agent for medical ultrasound (US) imaging comprising microbubbles, and is currently manufactured as a freezedried product, meaning that the end user (hospital nurse or pharmacy) has to reconstitute the product with water prior to use. Furthermore, the freezedrying process is lengthy (limiting manufacturing capacity), costly and also entails the emission of a powerful greenhouse gas. The primary objective of the current project is to develop and obtain regulatory approval for a Ready-to-Use, liquid formulation of Sonazoid, with the aim of providing a very significant increase in manufacturing capacity, a reduction in emission of green-house gases, a reduction in manufacturing costs and a more user friendly product. Since project start-up in October 2022, R&D efforts have focused on establishing a small-scale manufacturing process and screening of a multitude of different formulations and container/closures (CC). A wide range of formulation parameters, vial and stopper qualities have been varied over a total of > 40 different batches. These have been evaluated for critical quality parameters (s.a. microbubble characteristics, purity, ultrasound properties etc.), storage stability and biocomparability vs the current Sonazoid product. The results from these studies will be the basis for choosing a final formulation for manufacturing scale up and regulatory documentation, which will start 1Q2025. So far, the results are promising; several of the tested formulation/CC combinations show properties/characteristics which are essentially equivalent to current Sonazoid, in addition to a storage stability which indicates that the requirements to such will be met.

Sonazoid is a world leading contrast agent for medical ultrasound (US) imaging, currently manufactured at GE Healthcare AS (Norway) as a freezedried product. It is also a primary component in PS101, a therapeutic drug product for Acoustic Cluster Therapy, currently being developed by EXACT Therapeutics (Norway) for treatment of solid cancers. Sales volumes of Sonazoid are forecasted to exceed the current manufacturing capacity at GE Healthcare in the long term future which, hence, needs to be expanded. A range of commercial and environmental benefits with a Ready-to-Use (aqueous) formulation of Sonazoid (RtU-S) has been identified including; a markedly increased manufacturing capacity; a reduced CO2 emission; manufacturing cost savings, and increased user friendliness vs. competitive products. The current project is hence directed towards developing and documenting RtU-S formulation for ultimate regulatory approval. The project contains 3 phases; a pre-formulation and screening phase in order to identify candidates for further development; a lead-candidate phase where one of these is selected for full development and; full development phase where upscaling is achieved and the necessary regulatory documentation generated. Primary end-points throughout the project will be current regulatory specifications, in addition to in-vitro and in-vivo characterization of US imaging attributes and therapeutic benefit in order to demonstrate biocomparability. In the partner constellation, GEHC will be project owner and provide R&D related to formulation, manufacture and analyses of RtU-S. EXACT will provide R&D related to US characterization and the use of RtU-S as part of PS101. Academic R&D providers at LabTAU (France) and NTNU (Norway) will generate the necessary biocomparability data.