Editorial Article: Streamlined formulation of mRNA-filled lipid nanoparticles with precise pumping technology

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Dr. Florian Glauche, product manager at KNAUER

As a relatively new drug delivery system, lipid nanoparticles (LNPs) have been increasingly recognized for their ability to encapsulate and transport complex active ingredients to target cells in the human body. This has led to a growing demand for their production, exacerbated by their pioneering role in the delivery of mRNA-based vaccines against the SARS-CoV-2 virus.

Critical to LNP production using impingement jet mixing is the precise and controlled injection of specific lipid formulations into flowing systems, a process that relies heavily on the accuracy and flexibility of dosing pumps throughout the pharmaceutical workflow.

In this article, we hear from Dr. Florian Glauche, product manager at KNAUER Wissenschaftliche Geräte GmbH, about the pivotal role dosing pumps play in this process and the features of KNAUER dosing pumps that support the mass production of high-quality LNPs containing active pharmaceutical ingredients such as mRNA.

Rising to new challenges

Following the onset of global vaccination programs to curtail the spread of COVID-19, pharmaceutical companies have been under immense pressure to meet the demand for vaccine production. Among the COVID-19 vaccines currently approved, mRNA-based vaccines represent the first large-scale use of mRNA and lipid nanoparticles in vaccination history, bringing unique challenges to these efforts. “Before the COVID-19 pandemic, the production of LNPs had only been performed on a laboratory scale, and for us at KNAUER, this subject was completely new,” explains Glauche. “As a result, we had to design, manufacture and validate a system for LNP production in a very short timeframe to provide our biopharmaceutical partners, who own the chemistry and the process, with customized hardware.”

Lipid nanoparticles are being used to encapsulate the mRNA-based vaccines, protecting them from degradation and improving their chances of uptake by cells in the body. However, their synthesis is a highly complex process and depends on the fast and reliable switching of liquids under tightly controlled conditions. “Scaling up LNP production is not simple, as the quality of LNPs is determined by multiple parameters, including the liquid flow stability, the mixer geometry and the fluid velocity profile,” Glauche adds.

In particular, very stable liquid flow and excellent mixing are essential to the process, requirements which KNAUER’s portfolio of dosing pumps are optimized to meet, asserts Glauche.

 “KNAUER dosing pumps precisely deliver fluids at a wide range of flow rates and pressures, and when used in combination with a mass flow controller, exceptional flow accuracy and precision can be achieved,” he says. “The resulting integration of the pumps and mass flow controllers into the process control environment ensures optimal conditions for lipid nanoparticle formation.”

Leveraging this technology, KNAUER has been able to quickly adapt to the needs of its pharmaceutical partners, helping them to accelerate the production and subsequent rollout of essential COVID-19 vaccines. Glauche summarizes: “Looking at where we are at right now, I think everyone at KNAUER has done an amazing job. Being able to deliver equipment for a crucial step in COVID-19 vaccine production makes us all very proud.” 

Supporting the wider workflow

In addition to dosing pump technology, KNAUER also offers chromatography solutions for the biopharmaceutical industry. “Vaccine production contains several chromatographic steps, and we support both quality assurance with our analytical HPLC systems and the purification of intermediates with our preparative systems,” says Glauche. “For GMP approval, we offer services including acceptance tests, such as factory acceptance tests (FATs) and site acceptance tests (SATs), as well as material documentation of the system’s wetted parts.”

Future outlooks

KNAUER dosing pumps are suitable for a wide range of applications within the process industry, from polymer production to the formulation of radiopharmaceuticals. As such, Glauche suggests one of KNAUER’s main priorities going forwards is reducing the environmental impact of its products. He concludes: “We have always produced long-lasting instruments, but today we consider many different angles to improve sustainability when designing a new product. Simplified maintenance and long-term availability of wear parts are just two examples of our efforts to decrease the carbon footprint of our devices, and we’re excited to build upon this in the future.”

Find out more about how KNAUER can support LNP production >>

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