Creating a genetic medicine manufacturing ecosystem: part 4

Consider the explosion in 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.

From little things big things grow

When a cognisant few 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 at the lab scale, but seamlessly and efficiently for global population volumes.

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, may be the key. It’s far from the glitzy and glamourous archetypal corporate we imagine, but rather a collection of clever engineers, scientists and pharma process control experts designing a new way to solve the puzzle.

Precision-engineered, crossflow micro-mixing 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 good 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.

Jennifer Huen of Beagle Scientific wrote a review of current and emerging technologies in her article ‘Fast, Controlled, and Consistent: An Exploration of Current mRNA Vaccine Production Technologies’.¹ Perhaps this is indicating the way forward.

Around the grounds

The article ‘RNA’s importance to Australia’², published last year in Lab+Life Scientist, largely focused on the beginnings of the UNSW RNA Institute. Clearly more funding is now being allocated — the NSW Government recently announced Australia’s first-of-its-kind $96 million RNA research and pilot manufacturing facility will be built at Macquarie University and operated by Myeloid Therapeutics.³

Following a multitude of meetings discussing this facility from the very early days of planning, former Minister for Health Brad Hazzard worked tirelessly to bring this to fruition for many years, likely before my letter in 2020 discussing the need to create a genetic medicine manufacturing ecosystem was forwarded to him by the Hon Gabrielle Upton. Hazzard stated, “Investing in RNA research and manufacturing will ensure NSW remains a world leader in the development of medical technologies and therapeutics, which will ultimately deliver better patient outcomes, particularly for cancer and rare genetic diseases.”³

This accomplishment includes the appointment of the CEO of Myeloid Therapeutics, Dr Daniel Getts — who was raised in the Shire, educated at the University of Sydney and has held a research position at the Centenary Institute. Getts said, “This partnership with NSW and its Health Infrastructure team for the creation of a state-of-the-art RNA manufacturing facility represents a significant milestone. It positions Myeloid to become a leading GMP manufacturer and developer of RNA-based immunotherapies across the globe.”⁴

Down the Hume to Canberra and the Shine-Dalgarno Centre for RNA Innovation integrates world-leading RNA biology research with advanced enabling infrastructure, allowing us to meet future biomedical challenges in partnership with industry, government and academia.⁵ This is continuing the legacy of the 1973 Nature article ‘Conserved Terminal Sequence in 18S rRNA May Represent Terminator Anticodons’⁶, as this ribosomal binding site in bacterial messenger RNA became known as the Shine-Dalgarno (SD) sequence. This year represents 50 years since this discovery, and Professor Thomas Preiss informed me of a terrific event — the Shine-Dalgarno Launch Symposium.⁷

The ecosystem continues to grow with the Queensland Government announcing a partnership with healthcare giant Sanofi to create a Translational Science Hub. Minister for Science Meaghan Scanlon stated, “This agreement will make Queensland science even more competitive by accelerating the commercialisation of local research by linking university partners with a global industry leader to test and develop new heath technologies.”⁸ This is capacity building which complements the brilliant work of the Translational Research Institute, Griffith University, The University of Queensland (UQ) and UQ’s BASE facility.

The continued funding from the Victorian Government, the location of the Moderna, Pfizer and CSL facilities, and the existing excellence at Monash University, the Monash Institute of Pharmaceutical Sciences, The University of Melbourne, the Doherty Institute, CSIRO, St. Vincent’s Institute of Medical Research, the Hudson Institute and RNA Victoria are creating an incredible stronghold on RNA science in Australia. I agree with a recent guest’s comments, hailing from the US and embedded in RNA science: “Melbourne is likely second only to Boston when it comes to RNA science in the world.”

What this suggests is that Australia can pivot, and build a thriving industry given the drive of the cognisant few. Let us not forget the ANZRPC (Australian and New Zealand RNA Production Consortium) — the original driving force of these incredible developments.⁹

Evolution

We are on the precipice of an explosion in local manufacturing of genetic medicines on a scale never seen before, with global equitable access. To do this, a material change in how the drugs or vaccines are manufactured will be necessary. Imagine 1500 litres an hour, translating to 58,000 doses of vaccine every minute — from something that can fit into a small briefcase.¹⁰ Now that really is ‘From Little Things Big Things Grow’.

^{1. Fast, Controlled, and Consistent: An Exploration of Current mRNA Vaccine Production Technologies. https://www.selectscience.net/application-articles/fast-controlled-and-consistent-an-exploration-of-current-mrna-vaccine?artID=57809 Accessed 6 Mar 2023}

^{2. RNA’s importance to Australia. https://issuu.com/westwick-farrowmedia/docs/lab_and_life_scientist_aug_sep_2022/26 Accessed 6 Mar 2023}

^{3. Global leader to operate $96 million RNA facility at Macquarie University. https://www.nsw.gov.au/enterprise-investment-trade/media-releases/global-leader-to-operate-96-million-rna-facility-at-macquarie-university Accessed 9 Mar 2023}

^{4. Myeloid Therapeutics and New South Wales (NSW) Government in Australia Announce Collaboration. https://www.myeloidtx.com/post/myeloid-therapeutics-and-new-south-wales-nsw-government-in-australia-announce-collaboration Accessed 9 Mar 2023}

^{5. The Shine-Dalgarno Centre for RNA Innovation. https://jcsmr.anu.edu.au/research/centres/sdcri Accessed 9 Mar 2023}

^{6. Conserved Terminal Sequence in 18S rRNA May Represent Terminator Anticodons. https://www.nature.com/articles/newbio245261a0 Accessed 9 Mar 2023}

^{7. 50 Years Shine-Dalgarno: The impact of RNA Science and Innovation. https://www.shine-dalgarno-symposium.org.au/ Accessed 9 Mar 2023}

^{8. Queensland and Sanofi to establish global vaccine hub. https://statements.qld.gov.au/statements/96732 Accessed 9 Mar 2023}

^{9. Creating a Genetic Medicine Manufacturing Ecosystem. https://issuu.com/westwick-farrowmedia/docs/lab_and_life_scientist_apr_may_2021/6 Accessed 9 Mar 2023}

^{10. The Product Development Journey, Micropore Technologies. https://youtu.be/1aaNwVTFCFg Accessed 9 Mar 2023}

Image credit: iStock.com/Design Cells