“The market for lipid nanoparticles really exploded during COVID-19,” says Alexander Aust, LNP manufacturing expert.
Alexander Aust, a consultant specialising in lipid nanoparticle (LNP) manufacturing, brings years of experience from companies like Sigma-Tau Pharmaceuticals and Exelead. His expertise spans from commercial liposomal drug products to cutting-edge mRNA and gene editing technologies.
In the latest PharmaSource podcast episode, Alexander explains why LNPs have become crucial in drug delivery, particularly for mRNA vaccines, and shares insights on manufacturing challenges, regulatory considerations, and future applications of this technology.
The Rise of Lipid Nanoparticles in Vaccine Development
LNPs became a critical component in mRNA vaccine development during the COVID-19 pandemic. Alexander explains:
“MRNAs ultimately gave everybody with COVID that ability to develop immunity. But mRNA is physiochemically negatively charged. One of the main building blocks of the lipid nanoparticle is a cationic lipid, which is positively charged. When mixed, this allows the lipid nanoparticle to completely form a lipid layer around the actual RNA and then form another on the outside.”
This encapsulation process protects the mRNA and facilitates its delivery into cells, making LNPs an ideal vehicle for mRNA vaccines.
Manufacturing Challenges and Scale-up Considerations
As companies look to scale up LNP production, they face several challenges. Alexander highlights:
“One of the ever-present challenges has been screening different lipids for specific purposes and conducting tests to make a small amount of sample go a long way. There was a void of applicable technology that could get down to really small levels for formulation optimisation.”
He also notes the complexities in transitioning from small-scale to large-scale production:
“You have to generally go from that microfluidic or smaller mixing process to a GMP batch scale. You have to switch the mixing technologies, which costs time and money. You have to make sure that when you’ve changed the manufacturing process, you haven’t changed the drug itself.”
Regulatory Considerations for LNP Manufacturing
While there are no specific FDA guidelines for LNP manufacturing, Alexander points to relevant documents:
“The FDA came out with a draft guidance for platform technologies. These platform technologies, meaning, what do you need to bring on a regular regulatory basis if you use this LNP that’s proven to deliver this mRNA and swap out the mRNA while the LNP is the same?”
He advises companies to be cautious when setting specifications:
“Don’t set your specifications too tight in the beginning, because you can always tighten them. The FDA doesn’t like it when you try to back them off.”
Future Applications and Innovations in LNP Technology
Alexander sees significant potential for LNPs beyond vaccines:
“Cell immune therapy, with CAR-T and everything else like that, has not even really been tapped yet. Being able to target the immune cells in immunotherapies is going to be huge.”
He also highlights the potential for personalised cancer vaccines and gene therapies:
“We’ll be able to take some sample from someone, sequence it, get your RNA, get it encapsulated, get it filled, get back to the patient in less than two weeks. I really see the gene therapy and gene editing market only ever growing.”
For those looking to innovate in the field, Alexander advises generating data in order to stand out.
“This industry is saturated in good ideas, but not in data.” he says.
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