Lipid Nanoparticle Manufacturing – Continuous vs. Microfluidics Batch Processing

Lipid nanoparticles (LNPs), spherical constructs less than 100 nm in diameter, are promising new drug delivery mechanisms offering significant advantages. When compared with traditional drug delivery methods, LNP delivery offers:

  • Superior drug encapsulation for a wide range of drug molecules;
  • Enhanced bioavailability ensures a larger portion of the administered dose reaches its target site, and by protecting the drug payload from degradation and rapid clearance, LNPs increase the concentration of the drug in the bloodstream, thereby enhancing its therapeutic efficacy;
  • Targeted delivery to diseased tissues while sparing healthy tissues to reduce systemic side effects and improve treatment outcomes;
  • Reduced toxicity because LNPs are composed of biocompatible lipids as opposed to toxic excipients or solvents used in some traditional drug delivery methods;
  • Stability and longer shelf life as their lipid bilayers protect the encapsulated active pharmaceutical ingredient (API) from degradation by enzymes and other environmental factors; and
  • Drugs can be released sustainably, reducing the need for frequent dosing, enhancing patient compliance, and maintaining a consistent therapeutic concentration of the drug in the body.

LNPs played a pivotal role in developing mRNA-based COVID-19 vaccines. Additionally, LNPs deliver chemotherapeutic agents directly to cancer cells, minimizing damage to healthy tissues and reducing side effects. LNP encapsulation of genetic material facilitates the delivery of therapeutic genes into target cells and offers potential treatments for genetic disorders and rare diseases. Also, because LNPs can cross the blood-brain barrier, they have tremendous potential for delivering drugs to the central nervous system to treat neurological diseases.

LNP manufacturing challenges

While LNPs are promising drug payload delivery mechanisms, microfluidics-enabled batch processing poses significant manufacturing challenges like high batch-to-batch variability that impacts products’ critical quality attributes (CQAs), laborious multistep processes, and the need for expert operators.

In addition, batch-to-batch variability presents challenges scaling production, difficulty controlling particle size and distribution,  frequent sterilization issues, and common barriers to complying with GMP and other regulatory requirements.

How DIANT Jet continuous LNP processing resolves batch manufacturing challenges

Unlike traditional microfluidics batch processing, DIANT’s technologies integrate, creating a continuous processing skid that eliminates the need for open transfers and human interaction.

Proprietary DIANT®  Jet turbulent mixing technology is at the forefront of the solution, optimizing production speeds by mixing lipids and nucleic acids at high speed to form uniform particle size LNPs efficiently. Built-in PAT via In Process-LSP’s NanoFlowSizer enables in-line particle size monitoring and control, ensuring product quality throughout DIANT’s closed-loop process.

DIANT’s systems are also customizable with add-ons to facilitate a truly continuous manufacturing process. Specifically, DIANT tangential flow filtration (2TFF) technology concentrates particles using a proprietary multi-stage flow system to reduce biofouling and allow for long-duration runs. DIANT systems can also incorporate an internal external modification (IEM) module enabling conjugation for precise tissue targeting, all within a closed system.

DIANT’s continuous processing-based technology is seamlessly scalable from the lab bench LARU system to the commercial LiFT processing skid. It is advancing nanoparticle manufacturing by facilitating highly scalable LNP production, resulting in:

  • High-quality drug products
  • Faster speed to market
  • Greater control during the manufacturing process
  • Smaller vessel sizes
  • Smaller footprint for equipment (and therefore facilities)
  • Less waste
  • Reduced costs

DIANT technology – poised to revolutionize LNP manufacturing

While LNP drug delivery offers significant advantages over traditional drug delivery methods, microfluidics-enabled batch LNP production is limited by batch-to-batch variability and scaling challenges. DIANT’s continuous processing technology overcomes these challenges, and regulators and industry are taking notice.

For example, in 2023, the US Food and Drug Administration acquired a LiFT system, and the agency is conducting hands-on internal research to understand the system’s operation better and possibly inform future approval processes and guidance.

DIANT continuous LNP manufacturing systems are quickly becoming the industry benchmark. The technology supports highly efficient production with uniform particle sizes, producing higher-quality drug products. Contact us if we might support your LNP development, formulation, or production journey.