Lipid nanoparticles have made a major impact on the pharmaceutical industry. At their core, lipid nanoparticles (LNPs) are delivery carriers that safeguard nucleic acids. As an integral part of recent mRNA vaccines, they are injected and transported to the intended site in the cell. Not only are LNPs a promising drug delivery platform (due to their capabilities of encapsulating proteins and amino acids antigens along with enhanced targeted delivery efficiencies, increased bio-availabilities, and controlled release capabilities) but they are also, in some cases, preferred adjuvants that are significantly influencing the development of next-generation vaccines and gene therapies.
Despite the many advantages of using Lipid nanoparticles as delivery systems, the pharmaceutical industry must address significant manufacturing challenges.
These challenges include:
- precisely controlled particle size/size distributions
- sterilization issues
- process repeatability and scalability
- regulatory requirements (such as cGMP regulations)
Particle size impact on LNP production
Although a superior drug delivery carrier, LNPs would not be as effective if they weren’t within certain particle size ranges. Particle size is a key factor in influencing absorption, content uniformity and shelf-life. Through particle size reduction, lipid nanoparticles achieve an efficient drug delivery system in which activities can reach and be released at their target site. This nanoparticle size reduction ensures product stability, so the final product is less likely to separate over time and therefore achieves a longer shelf life resulting in less product waste.
The strength of Microfluidizer® technology is its ability to achieve small, uniform LNPs on the nanoscale. Microfluidizer’s® technology delivers the highest shear forces and applies it consistently. At the center of this technology is Microfluidics’ Interaction Chamber™. The material processed through the Interaction Chamber™ is exposed to extreme shear rates so it requires fewer passes to achieve particle size reduction. This efficient processing saves time and money.
Sterile Filtration Challenges
As an injectable, pharmaceutical companies must evaluate sterilization consideration for their vaccine manufacturing which is often time-consuming and expensive. Due to Microfluidics’ small and narrow particle size capabilities, cost-efficient and gentle sterile filters can be applied. Since small nanoparticles can pass through sterile filters without clogging or losing product, production interruptions are preventable.
How can LNP production be replicated from research and development results to global distribution with same results achieved batch-to-batch?
Developing a new pharmaceutical is costly with recent studies estimating the average research and development cost per new drug to range from under $1 billion to more than $2 billion per drug. According to the US Congressional Budget Office, the top ten pharmaceutical companies spent over $82 billion on R&D in 2019 alone.1 With such a substantial investment made in R&D, scale-up manufacturing is a top priority in the pharmaceutical industry since achieving results in the laboratory are only useful if they can be duplicated for global distribution. Going from a few thousand doses to millions of doses per day must be seamless and the results must be consistent. Existing small-scale processing cannot meet demand and process improvements are necessary prior to full production scale-up.
Microfluidics equipment processes every batch of material under the same conditions. The fixed geometry Interaction Chamber™ ensures consistent, replicable processing with less energy to achieve the target LNP (or nanoparticle) properties. By precisely controlling the pre-mixing procedure and maintaining the same temperature conditions, the same particle size results are duplicated batch-to-batch. To scale up, the number of micro-channels increase within the Interaction Chamber™ on the processor, so repeatable, linear results can be scaled from R&D to pilot scale to production scale. In one example, a vaccine adjuvant formulation was successfully scaled up with a production scale Microfluidizer® processor in a small cGMP manufacturing facility to achieve enough batches to produce 5M doses of vaccine in just one day.2
Addressing cGMP compliance
Of considerable importance, from lab-scale to production scale, Microfluidics offers a full range of cGMP-compliant processors to specifically address the needs of the pharmaceutical and biotech market. Our team of engineering experts are updated on design regulations from required materials to cleanability and maintenance factors of each cGMP-compliant processor. Our equipment meets all sanitary equipment design and control system requirements thereby guaranteeing the quality of the product. Our engineers work with top biotech and pharmaceutical companies to provide the level and complexity of controls needed to meet all government regulations for their nanotechnology goals.
As lipid nanoparticles continue to play a key role in the medical field, top pharmaceutical companies must address the challenges of this unique delivery platform. From particle size reduction, sterile filterability, scalability and regulatory requirements, Microfluidizer® processors achieve superior LNP production. With decades of success working with top pharmaceutical companies, Microfluidizer® technology has proven to be a trusted technology to meet today’s demanding nanotechnology challenges.
References and related materials
- 1cbo.gov https://www.cbo.gov/publication/57126
- 2Pharmaceuticals | Free Full-Text | Squalene Emulsion Manufacturing Process Scale-Up for Enhanced Global Pandemic Response (mdpi.com)
- Solvent-free production methods for liposomes and lipid nanoparticles
- Using Lipid Nanoparticles to Design Vaccine Delivery Systems
- How does Microfluidizer technology support vaccine development FAQ