Translating Nanomedicine Potential into a Scalable Reality with Flow Manufacturing
Mark van Eldijk, Business Unit Director, Nanomedicines, Ardena
Nanomedicines are revolutionising drug development by enhancing precision, control and therapeutic performance. This article explores how flow manufacturing overcomes the scalability and quality challenges of nanoparticle production, enabling consistent, reproducible results from lab to commercial scale. With expert insight from Ardena, it highlights strategies to ensure reliable, scalable nanomedicine manufacturing.
Nanomedicines are transforming modern drug development by enabling therapies to act with greater precision and control. As formulations become more sophisticated and the market continues to expand, developers face growing pressure to ensure nanoparticle quality and scalability. Achieving this balance between innovation and manufacturability demands production approaches that deliver consistent performance and deep process understanding.
In this article, Mark van Eldijk, Business Unit Director Nanomedicines, at Ardena, explores how flow manufacturing is reshaping nanomedicine production, offering a more controlled, scalable and reproducible path from laboratory design to commercial supply, and helping to bring advanced therapies to patients with greater reliability.
The growing role of nanomedicines in modern drug development
At the intersection of materials science and medicine, nanomedicines are reshaping how therapies are designed, delivered and controlled. By applying the tools of nanotechnology to drug development, researchers are creating medicines that can act with exceptional precision.
At its core, a nanomedicine is a therapeutic that contains nanoscale components, typically between 1 and 100 nanometres in size. With different material classes, lipids, polymers or metals, with precise control over particle size, composition and surface characteristics, developers can tailor nanoparticles to achieve specific functions. The diversity of nanomedicine platforms reflects the wide range of therapeutic goals they can address:
Lipid-based nanoparticles
Including liposomes and lipid nanoparticles (LNPs), these systems are widely used in gene delivery and vaccine formulations. They can efficiently encapsulate and protect nucleic acids or small molecules until they reach their target site.
Polymeric nanoparticles
Formed from tailored polymers, polymeric nanoparticles and dendrimers enable controlled or targeted drug release, supporting therapies that benefit from sustained delivery, such as those used to treat cancers or chronic diseases.
Metal and metal oxide nanoparticles
Comprising materials such as gold and iron oxide, these nanoparticles are primarily used in imaging and targeted cancer therapies, where their optical and magnetic properties enable precise localisation and treatment.
Each of these nanoparticle systems leverages nanoscale engineering to optimise how a formulation interacts with biological systems, influencing circulation time, cellular uptake and biodistribution to deliver a defined therapeutic response.
Meeting the demands of the expanding nanomedicine market
Nanomedicines have already demonstrated meaningful clinical success across multiple therapeutic areas. Applications now span oncology, chronic disease management, regenerative medicine and gene therapy.
More than 100 nanomedicines are already approved, and over 550 candidates are in clinical development, marking the sector’s steady evolution from early innovation to established industrial maturity. The growing diversity of nanomedicines is mirrored in the expansion of the global market, valued at approximately USD 265.9 billion in 2025 and projected to reach USD 632.1 billion by 2034, representing a compound annual growth rate of 10.1%.
As demand for nanomedicines expands, manufacturing has become a defining factor in realising their full potential. Meeting market and clinical expectations requires production processes that deliver consistency, scalability and precise control over complex nanoparticle systems. However, achieving this level of precision can be challenging, and developers and manufacturers must carefully consider the optimal approach for their nanomedicine production.
Flow manufacturing of nanomedicines
Conventional batch production often struggles to deliver the level of precision and reproducibility needed to maintain consistent nanoparticle quality at scale. Even small variations in process parameters, such as temperature or mixing dynamics, can alter key particle attributes, which in turn influence clinical performance.
Flow manufacturing offers an effective alternative. Rather than processing materials in separate steps, this method maintains a continuous flow of reactants through controlled environments, allowing nanoparticle formation to occur under steady-state conditions. The benefits of flow manufacturing are most evident in two key areas:
Scalability
Scalability remains one of the most significant hurdles in nanomedicine manufacturing. In traditional batch systems, scaling from laboratory synthesis to production quantities often requires complete process reoptimization because reaction kinetics, mixing efficiency and heat transfer behaviour change with reactor volume. This scale dependence increases development timelines and introduces variability across stages of production. Flow manufacturing minimises scalability issues, as once process parameters are optimised at a small scale, they can typically be translated directly to higher-throughput systems with only minor adjustments.
Output with flow manufacturing can also be increased by extending run time or operating multiple flow channels in parallel. This linear scalability enables developers to transition from gram-scale to kilogram-scale production without redefining critical process conditions.
Continuous flow systems also enable faster, more flexible scale transitions between early development and clinical manufacturing. As the same process parameters can be retained, formulation consistency is maintained across the product lifecycle. For nanomedicines, such predictable scalability provides a major advantage, ensuring adequate material supply for clinical phases without compromising quality or timelines.
Quality
Quality in nanomedicine manufacturing depends on achieving uniformity at the molecular and particulate level. Flow manufacturing strengthens quality assurance through continuous, tightly controlled operating conditions. Once steady-state operation is reached, process parameters such as flow rate, temperature and concentration remain constant, reducing variability and improving reproducibility across production runs.
The small internal dimensions of flow reactors create high surface-area-to-volume ratios, typically improving heat and mass transfer compared with batch reactors. This prevents local fluctuations in temperature or concentration that can lead to uneven particle formation. As a result, nanoparticles exhibit narrower size distributions and consistent encapsulation efficiency, as well as stable physicochemical properties, all of which contribute directly to clinical performance and regulatory reliability.
Additionally, flow systems lend themselves to real-time process monitoring and control. Inline analytical tools can track parameters such as particle size or composition during production, allowing operators to adjust conditions immediately if deviations occur. This capability supports a quality-by-design (QbD) approach to nanomedicine manufacturing, one that ensures quality is built into the process rather than tested into the final product.
Selecting flow technologies for nanoparticle production
Realising the full potential of flow manufacturing in nanomedicine production depends on selecting the right system configuration for the specific nanomedicine being produced. While the principles of continuous processing remain consistent, the performance of a flow setup can vary greatly depending on the choice of pumps, mixing geometry and reactor design. Understanding how each component influences particle formation is, therefore, critical to achieving the desired product characteristics and maintaining flexibility as formulations evolve.
Flow systems, whether commercially available or custom-built, typically share three key functional elements:
Pumps
Precision pumps ensure a continuous, controlled flow of reactants. In nanomedicine production, this is typically achieved using either syringe pumps or high-pressure dosing pumps. Syringe pumps are favoured in early formulation work, where smaller volumes and high dosing precision are critical for screening process parameters. High-pressure dosing pumps, by contrast, enable higher throughput and stable operation over longer production runs, making them suitable for scale-up and GMP environments. Selecting between the two depends on the desired throughput and process stability.
Mixing configurations
The mixing configuration determines how materials combine to form nanoparticles and directly affects particle size and uniformity. Commonly used designs in flow manufacturing include: microfluidic chips, T-junction mixers, impingement jet mixers and multi-inlet vortex mixer (MIVM). Microfluidic systems employ microscale channels that enable rapid, controlled mixing, making them ideal for fine-tuning formulations during early development. T-junction mixers are the simplest mixer units and provide scalable manufacturing. Impingement jet mixers and multi-inlet vortex mixers also provide scalability but offer improved mixing. The impingement jet mixers operate by colliding liquid streams at high velocity to create intense turbulence, achieving efficient mixing at higher flow rates, a configuration well-suited to larger-scale nanoparticle production.
A modular design
The overall flow architecture determines the system's flexibility and cost-efficiency. Commercial platforms often feature modular designs, allowing pumps and mixers to be interchanged as process needs evolve. This adaptability supports iterative optimisation without major capital investment. As development progresses, custom-built flow systems can be tailored to specific formulation and throughput requirements, providing improved control, process robustness and long-term efficiency.
A clear understanding of how each component interacts is fundamental to process design. Early assessment of system architecture helps developers balance performance, flexibility and cost-effectiveness, ensuring that processes established during formulation can be efficiently scaled to clinical and commercial manufacturing. Partnering with experienced contract development and manufacturing organisations that understand flow technologies and system components can give developers a valuable edge, helping translate strong design principles into reliable, scalable nanomedicine production.
A case study: Evaluating a multi-inlet vortex mixer (MIVM) for nanoparticle production
Understanding the influence of flow system design on nanoparticle formation was central to a study carried out by Ardena using a multi-inlet vortex mixer (MIVM). This mixer combines multiple inlet streams within a confined chamber, generating rapid vortex mixing that promotes uniform contact between solvent and antisolvent phases. Ardena applied the system to produce a liposomal formulation comparable to a liposomal formulation of doxorubicin, assessing how total flow rate, solvent ratio and lipid concentration influenced particle characteristics.
Results showed clear relationships between process conditions and product quality. Increasing flow rate reduced particle size until turbulent flow was reached, while higher antisolvent ratios and lower lipid concentrations produced smaller, more homogeneous liposomes. All test conditions yielded polydispersity index (PdI) values below 0.2, confirming consistent particle uniformity.
The study demonstrated how detailed knowledge of mixer geometry and flow behaviour supports informed component selection and process optimisation, key factors in achieving scalable, reproducible nanomedicine manufacturing.
Preparing for the future of nanomedicines
Looking to the future, the nanomedicine space can be expected to continue advancing rapidly, with increasingly complex formulations and expanding therapeutic applications. As innovation accelerates, the challenge will be to translate these scientific advances into consistent, scalable products that meet both clinical and commercial expectations. Achieving this will rely on manufacturing approaches that combine precision, reproducibility and control.
Flow manufacturing provides a strong foundation for this next stage of development. By maintaining continuous control over critical parameters, flow systems deliver the consistency and flexibility needed to support the production of complex nanoparticle formulations while meeting evolving regulatory standards for quality and process understanding.
However, realising these advantages relies as much on expertise as on technology. Working with partners who combine practical experience in flow manufacturing with a deep understanding of system components enables processes to be designed and scaled with confidence and precision. As demand for nanomedicines grows, such collaboration will be key to delivering advanced therapies efficiently, reliably and at the scale needed to reach patients worldwide.
References:
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3. Hertig, J.B., Shah, V.P., Flühmann, B., Mühlebach, S., Stemer, G., Surugue, J., Moss, R. & Di Francesco, T. (2021) ‘Tackling the challenges of nanomedicines: are we ready?’, American Journal of Health-System Pharmacy, 78(12), pp. 1047–1056.
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Author Bio
Mark van Eldijk is the Business Unit Director of Nanomedicines at Ardena. He earned his PhD for his work on biopolymer-based nanoparticles and completed a postdoctoral fellowship at the California Institute of Technology. Mark joined Ardena in 2016 as a scientist and project leader before transitioning into business development for the company’s nanomedicine services. Since January 2023, he has served as the Business Unit Director of Nanomedicines.
