A Better Way to Nanoparticle Production: The Micropore AXF System

Efficient nanoparticle production is vital for advancing treatments to GMP standards. Lipid Nanoparticles (LNPs) show great promise in combating cancer and infectious diseases. However, the choice between single-use and reusable systems has long been problematic until the emergence of the Micropore AXF System. This pioneering technology, born from Micropore Technologies, a spin-out from Loughborough University, represents decades of research. Originally designed for various industrial applications, its potential for producing LNPs was realised during the COVID-19 pandemic. Collaborative work with Professor Yvonne Perrie from the University of Strathclyde showcased its remarkable Encapsulation Efficiency (EE) and versatility across different flow rates.

Current Methods and Challenges

Many leading mRNA vaccine manufacturers favour traditional methods such as confined impinging jet mixers (CIJMs), yet these methods face challenges including limited control, predictability and stability issues. On the other hand, microfluidic devices, while suitable for small-scale development, may encounter issues like deformation and leachable release. Also, scaling up requires adjustments to the mixing architecture to preserve a consistent Reynolds number, Dean number, and laminar flow conditions, posing difficulties in maintaining product consistency due to flow rate limitations.

Simplify Production at all Scales: At the heart of the Micropore AXF System lies a deceptively simple yet remarkably powerful principle: single-pass crossflow membrane emulsification. This innovative approach, engineered with precision-drilled 316 stainless steel membranes, enables precise control over particle size and uniformity across a diverse range of formulations including those in solvents. Through rigorous experimentation and validation, researchers have unlocked the predictive equations defining drop size as a function of shear stress, laying the foundation for scalable and reproducible nanoparticle production.

Practical Validation: Translating laboratory success into real-world applications, Micropore Technologies together with ATA Scientific collaborated with the University of New South Wales RNA Institute, Sydney, Australia. The Micropore Mini was set up with a simple syringe pump. An SM-102 formulation was created encapsulating RNA produced on site, which demonstrated remarkable results, with EE exceeding 96%. Meanwhile, ongoing collaborations with the University of Strathclyde continue to push the boundaries, achieving EE nearing 100%. It is worth noting that there is a significant cost attributed to every 1% drop in EE in the context of GMP production.

Scaling New Heights: As the demand for nanoparticle production continues to surge, the product consistency in production scale up remains a critical consideration. Herein lies the true power of the Micropore AXF System — the ability to seamlessly scale from 200 microlitres to litres without the need for consumables or cumbersome modifications. From the AXF-Mini to the Horizon™ m, a fully CFR 21 Part 11 compliant GMP production system is capable of production volumes of 2000 Litres / hr, custom built to client specification for capacity, feed system (pumped or pressure), full DQ / IQ / OQ / PQ support and PLC Integration. Whilst this is impressive, consider it is the smallest version of the AXF. The range is astonishing. The AXF-1 has a total flow rate of 2000 mL / min. Extend the AXF-1 to an AXF-4 and we begin to approach pandemic readiness. Micropore Technologies is working on resolving another major bottleneck in the production of nanomedicines. Not yet developed fully, but seductively intriguing, imagine using the AXF system as a single pass Tangential Flow Filtration.

Democratising medicine

AXF technology offers an opportunity for researchers seeking to explore novel carriers and delivery modalities, unencumbered by the constraints of traditional methods. For more information, please contact ATA Scientific Pty Ltd (phone: +61 2 9541 3500, email: enquiries@atascientific.com.au and website: www.atascientific.com.au).

_References

_{1. New Horizons in Lipid Nano Particle Production: Micropore webinar August 2021. https://www.youtube.com/watch?v=SP_4zLMzGlc}

_{2. Holdich R., Dragosavac M., Williams B., Trotter S. "High throughput membrane emulsification using a single-pass annular flow crossflow membrane" AIChE Journal, Volume: 66, Issue: 6, DOI: 10.1002/aic.16958}

_{3. WHITEPAPER: A better way to create nanoparticles for in vivo treatments. https://www.atascientific.com.au/a-better-way-to-create-nanoparticles/}