02 9541 3500Simplifying Large Scale Genetic Medicine Manufacturing
Consider the explosion Nanomedicine where huge advances are being made daily. Under the veneer of global acceptance is the growth of a few giants whose products were perfectly matched to the emerging needs of the pandemic. Their juggernaut continues with little indication it will slow. A key driver is the Pandora’s box of opportunities now possible to address a multitude of diseases currently untreatable.
When a cognisant few identify, recognise and act to make material change to the accepted paradigm it echoes the sentiment of Paul Kelly’s classic song ”From Little Things Big Things Grow”.
What is needed is an elegant disruptor to influence the market, something to resolve what seems to be the only choice in Nanoparticle production, something that can encapsulate the RNA and other molecules not only in the lab scale, but do so seamlessly and efficiently for global population volumes. Imagine 1,500 Litres an hour, translating to 58,000 doses of vaccine every minute – from something that can fit into a small briefcase!
What is Micropore Technologies?
Micropore Technologies is a UK based company with its roots in micro-mixing and emulsions expanding developments in the fundamental understanding of crossflow mixing technology research at Loughborough University. Far from the glitz and glamourous archetypal corporate we imagine but a collection of clever engineers, scientists and pharma process control experts designing a new way to solve the puzzle. Tucked away in a former chemical company’s site on the Tees, near Middlesbrough is a rich history of scientific endeavour that has served the UK and indeed the world well. Fitting yet another discovery emanates from here.
Advanced crossflow (AXF™) mixing has solved the problem of how to create micro and nano-spheres, emulsions and crystals with a very narrow size distribution around a chosen size with a robust, cost-effective manufacturing-scale technology. Whilst firmly rooted in micro-emulsions the team at Micropore answered the call of the pandemic tweaking the technology to produce Lipid Nano Particles (LNP) that encapsulate genetic material with efficiencies over 95%, peptides and small molecules. Micropore’s precision engineered, crossflow micromixing equipment allows for thorough, reproducible nano-formulation at scales ranging from microlitres up to hundreds of litres using gentle laminar flows. The intuitive design and stainless-steel construction make GMP production of narrowly dispersed, accurately sized nanomedicines easier than ever before.
Given such a small footprint required and the simplicity of design, this will likely be the future of production; no need to build a factory even if it is a Flex Factory! This technology makes a deal of sense, in a GMP setting it is Clean In Place (CIP) or Steam In Place (SIP) – making it possible to achieve without the need to continuously buy consumables at exorbitant prices of hundreds of thousands of dollars just to run a single batch.
Global Leaders In Lipid Nanoparticle Production
Recognising global leaders in LNP creation and research were close by, they collaborated with The University of Strathclyde and a giant in this field Prof Yvonne Perrie. Yvonne stated the AXF has “A true workhorse capability. Easy to operate and very stable in operation”. Her research also found there was “No mRNA degradation in LNP production using AXF™ advanced crossflow mixing”. It is ticking fundamental boxes, but what about scaling up?
There are a few platforms that create excellent lab scale LNPs that may be parallelised to create higher volumes. Some alter the dimensions to achieve higher volumes, much like increasing the diameter in microfluidic channels. Others stack a multitude of lab scale systems to attain the desired outcome. Essentially, they all experience the ‘microfluidic roadblock’, not purposefully, but as a result of a few laws in fluid dynamics and the desire to expand capacity using the same conditions employed to create lab scale batches. I recall seeing a program during the pandemic exploring a Pfizer facility where their vaccine was produced, starkly, I recall what could be described as a warehouse with enormous racks and rows of hundreds of pumps and Impinging Jet Mixers. I pondered how on earth are they controlling size, PDI, encapsulation amongst a myriad of other parameters? The enormity of this project was astounding and a feat of intent. The world certainly gained from this endeavour. I can’t help but admit I also felt there must me a more efficient way.
When we discovered Micropore serendipitously, I knew they were an answer.
Micropore differs from all the other technologies, consider they started with volume and worked backwards to lab scale. Envisage a 316 stainless steel pipe with another pipe with 100s of 1000s of electropolished holes inside (called a membrane), attach 2 fluid streams, one as a continuous phase through the pipes and one at 90 degrees – forcing the second stream through the membrane into the continuous phase. Brilliantly engineered, so simply by design. You can put several together to achieve 1,500 L/hour, or you can make a Mini version and run from 600 µl up. Therefore, lab scale and population scale in something that as noted previously, can fit into a small briefcase!
To develop nanomedicines requires a deal of research, countless formulations and tweaking to fine tune not only the drug but the carrier such as a lipid encapsulating it. Each iteration will need to be produced and analysed. This likely equates to 100’s of runs and in microfluidic systems this may be tens of thousands of dollars in consumables such as cartridges to achieve the candidate for further development. There are no consumables in the Micropore system aside from a few PTFE ‘O’ rings. And the membrane is used over and over, it lasts for years – it is stainless steel after all. Micropore Technologies recognised the need to build a system that will not only direct LNPs created into a test tube but assist in the development of the formulation. The result is aptly named, the Pathfinder. Imagine you can ramp up through a range of flow rates collecting samples into a 96 well plate as you go, effectively running over 90 experiments in less than a minute! Now that is accelerating research and development!
Perhaps we should understand the Micropore Technologies’ corporate culture as this is incredibly important when accessing the organisation and investing in their technology. The CEO received an MBE from the newly minted King of England – the MBE was awarded by the Queen, but COVID got in the way of the ceremony. Notably the Chairman of their board also has an MBE- I understand you don’t find these in a cereal box. From what I have observed, their actions match their ethos to ‘improve life by delivering innovative technical solutions for better & more affordable products’.
The Micropore AXF system is promising to be a true in country manufacturing option- think Island nations – poor countries – lets democratise medicine … Again. With this in mind, it is fitting to use the Paul Kelly protest song, we can stand up against a few global giants trying to control what it will cost to produce medicines.
For further information call Peter Davis, Applications Specialist, T: 02 9541 3500 or email pdavis@atascientific.com.au