Finer than sand

Production Innovation never stops. Finer than sand Text Michael Mildner and Qureshi Shamshuddin. Photos and Videos Lemonic. As the designated launch site for this innovative covalent binder, the Novartis Technical Operations site in Ljubljana has successfully integrated state-of-the-art wet-media milling technology to achieve nano-particle precision. This advanced capability not only enhances the molecule’s solubility and bioavailability but also positions the Ljubljana site as a key contributor in accelerating the delivery of novel therapies to patients worldwide.

An operator inspects the solution containing the drug substance and excipients using high-intensity light to ensure that it is fully dissolved and free of any agglomerates. This process is followed by the wet-media milling step.

At the core of the manufacturing process is the wet-media mill, a critical piece of equipment that enables particle size reduction. During this step, as the drug substance enters the mill, it undergoes a remarkable transformation: Powerful, precision-engineered milling reduces the particles to an extremely fine size. This significantly enhances bioavailability by accelerating drug dissolution. It is a shining example of how advanced technology, expert craftsmanship, and scientific innovation come together to deliver smarter, faster, and more impactful medicines.

Inside the wet-media mill, zirconia beads act as the grinding media that mechanically reduce the drug substance to its targeted particle size. Before every production run beads are undergoing inspection.

After carefully assembling the wet media mill and verifying the quality of the prepared solution, the operator records and documents all the completed steps performed in the manufacturing execution system.

To prevent the grinding media beads from entering the drug product during milling, a specially designed four-layer sieve cartridge is installed inside the wet-media mill. This high-precision component features a 50 µm (0,05 mm) mesh, providing an effective barrier while allowing the processed suspension to flow through seamlessly.

During the wet media milling process, operators monitor the critical process parameters to ensure optimal performance. The operator closely observes the flow of the suspension.

A small glass observation window allows operators to continuously monitor the closed recirculating system throughout the milling operation. An entire batch of approximately 175 kilograms is cycled through the wet-media mill around 80 times before the final particle size process is finalized.

Operators and technicians Tilen Bučar, Rok Zajc, Alen Pivk, Safet Zahirović (from left to right) are thoroughly trained to ensure the quality, safety and efficacy of the drug product.