RNA manufacturing has, throughout its history, been an area of considerable difficulty for pharmaceutical manufacturers owing to the long development periods and high associated costs. These limiting factors often stifle the commercialisation of such products, with the medicines that do make it to market being unaffordable or unavailable for a significant proportion of the global population.
Therefore, the need to optimise the in vitro transcription (IVT) process, which facilitates RNA production, is profound. Enhancing the development process with AI has been proven to be successful and, now, Exothera believes it has cracked the procedure from end-to-end with its novel platform.
To find out how Ntensify can enhance productivity, reduce costs and accelerate development times, Annabel Kartal-Allen spoke to Darren Leva, Chief Business Officer at Exothera.
Who is Exothera?
Exothera is a Belgian contract development and manufacturing organisation (CDMO) that specialises in the production of nucleic acids and viral vectors. The company has access to multiple novel manufacturing technologies via its parent company: Univercells.
And, with this under its belt, the company endeavours to accelerate discovery and optimise process development to get therapeutics to a wider group of patients quicker.
Reducing costs
Businesses need to balance production costs with profit, with this concept being particularly prevalent in the pharmaceutical industry owing to the intensity of regulations and extended development times. Therefore, slashing costs is often paramount to driving success:
“When discussing the price of goods,” notes Darren, “our platform allows for a dramatic reduction — probably around half. When you think of running a process for a sizeable clinical trial, or even just at commercial scale, you’re able to deliver therapeutics to places where it was previously not economically viable.”
Lowering production costs also allows companies to allocate these funds towards other initiatives, as well as giving them the option to minimise therapeutic prices for the public: “Depleting costs in this way allows you to make different financial decisions. With more money available in the pipeline, it will suddenly make financial sense to treat a patient population in Africa with a vaccine that would usually be targeted at a more developed region.” 
Darren Leva, Chief Business Officer at Exothera
In a rare disease context, the cost of goods is heavily scrutinised because of the expenses associated with personalising medicines:
“Producing one customised therapeutic per patient is an expensive and laborious method compared with manufacturing generalised medicines. Bringing down the cost of these methods and enhancing their process efficiency greatly benefits patients
whose lives may depend on it.”
Reducing the hassle of scaling up
Creating RNA products on a large scale often involves procedure alterations, which can cause extensive commercialisation delays. However, scalability is not a factor when utilising Exothera’s technology: “With Ntensify, you never have to scale-up. You're always running the same volume, just in multiple reactions that are running in parallel.”
Ntensify allows companies to produce anything between a milligram and 12 grams of RNA, which can allow for adjustments depending on business requirements: “Although the equipment size will be contingent on the manufacturing scale, everything else is the same. Smaller equipment can be supplied for organisations focusing on ultra-rare diseases, as you’re likely to be working on small
patient cohorts. However, to convert to a medium or large market, the only necessary alterations
would be to source larger equipment."
"This allows for a seamless shift from a miniature manufacturing context to developing a vaccine at commercial levels within a short time. The flexibility of the platform means that companies of all sizes can optimise their RNA production capabilities.”
“When the platform is running, it’s all robotic, so up or downstream elements can be combined into one piece of equipment. Instead of running a single batch — such as in a vessel — you’re running a batch in small tubes and it scales out. You could be running ten 20 mL tubes in parallel robotically. They’re then pooled together at the end after the purification step.”
Expediting development
In general, IVT involves an extended process development period and necessary time to determine how to optimise scalability. This can hold manufacturers back from releasing products rapidly, which may discourage innovation. Darren explains how Exothera’s procedure can work to ameliorate these issues:
“Because Ntensify is standardised, it means that any mRNA or assay RNA product can be used, with an identical process used for any product. Eliminating one aspect of process development and scale-up, which can take up to 2 years to complete, both saves time
and greatly reduces the associated costs. Companies can get therapies to patients years quicker and that’s a big deal.”
Beyond development and scale-up, the manufacturing procedure has also been optimised to increase speed, Darren states: “Just from a process perspective, running the equipment takes half the time of a standard IVT reaction. The ability to process specimens in parallel, with purification at the end and then pooling, saves a lot of time. This is true for very small-scale material all the way
up to commercial use … even at the pandemic level.”
Cleaner and cheaper purification
Another benefit of this platform is its associated purification method. Darren continues: “The usual methodology in IVT is to use standard purification columns that involve multiple steps. Because our process is clean on the upstream and has been optimised, we can use beads for purification instead. This allows for a sizeable reduction in the cost of goods because of the decrease in
material use.”
The multi-contextual feasibility of using the Ntensify platform
The possibilities are endless in RNA production and can offer patients novel treatments that can vastly improve quality of life: “The obvious application of RNA that’s been exploding in popularity recently is in vaccines. Personalised cancer immunisations are huge now, as targeting genetic aberrations directly related to the patient’s disease pathology could notably enhance patient prognosis and standard of life."
"Reducing production costs whilst enhancing process efficiency could get therapeutics to patients whose lives depend on it. Another industry focus is on RNA therapeutics that modulate the genes implicated in specific diseases; this drug type is becoming
more prevalent in current clinical trials. It’s a space to watch.”
