The success of the mRNA vaccines for COVID-19 led to explosive growth in lipid nanoparticle (LNP)-mediated drug delivery for RNA vaccines and therapeutics. As these projects scale into clinical trials and, eventually, commercialization, developers will be challenged to ensure consistency in LNP formulation as the necessary quantities increase.

Cytiva is addressing that issue by adding the commercial formulation system with NxGen™ technology to its NanoAssemblr® family of systems. It produces between 0.5-liter and 400-liter batches of LNPs, enabling ample quantities for commercial production as well as appropriate quantities for clinical studies, thereby minimizing process development during scale-up.

One Tech Ensures Scalable Mixing

“Cytiva’s NxGen technology…enables controlled, reproducible mixing conditions that employ the same mixing architecture across a scalable family of formulation systems designed for all stages of drug development, minimizing process development and helping accelerate time to market,” Scott Ripley, PhD, nucleic acid therapeutics and precision nanosystems leader, Cytiva, tells GEN, adding that biopharma developers and manufacturers can be assured of the formation of consistent nanoparticles that maintain critical quality attributes throughout development.

The NanoAssemblr® commercial formulation system was designed to enable efficient changeover and robust manufacturing processes for the clinical and commercial production of lipid nanoparticles under cGMP conditions, say officials at Cytiva.

The NanoAssemblr commercial formulation system relies upon the same NxGen mixing technology used in the NanoAssemblr® Ignite™ (for preclinical development) and Blaze™ (for process development) “… allow(ing) the same fluidic conditions to be scaled from flow rates and batch sizes appropriate for preclinical to commercial manufacturing,” Ripley says. The mixing system uses a series of low-pulsation pumps to precisely control flow rates, enabling consistent mixing parameters for reproducible self-assembly of LNPs.

This new addition, he says, “enables high flow rates required for large-scale production batches with built-in automation that standardizes GMP manufacturing workflows.” That includes automated priming, calibration, formulation and in-line dilution to simplify GMP manufacturing and help reduce errors; in-process flow rate monitoring to provide real-time feedback; and intuitive software to enable electronic batch records (pending third party audit).

The NanoAssemblr commercial formulation system’s “single-use flow path reduces the need for sanitizing and performing cleaning validation between production runs while minimizing the risk of cross-contamination, which is particularly important for genomic medicines in which trace amounts of nucleic acids would impact the quality of the drug product,” he says. The flow path can be installed and ready in less than one hour, thus providing flexibility to support multi-product and multi-process workflows. The system can be integrated with Cytiva’s FlexFactory single-use manufacturing line.

The NanoAssemblr commercial formulation system is expected to ship in Q1 2024.

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