35 TWENTYFOURSEVENBIOPHARMA Issue 1 / March 2025 INDENA The GMP plant is being expanded in steps, starting from a first revamping in early 2024, then with further upgrades in the beginning of 2025. This expansion will allow the plant to enlarge the capacity of reactions/chemical synthesis up to ten times the actual capacity, produce larger scale HPAPIs obtained by both synthesis and purification (small molecules to OEB5) and offer higher production capacity for products actually made in other departments. More technologies have been added for the chemical synthesis and purification of APIs and HPAPIs: centrifugation under containment (reverse bag centrifuge); reactor loading under containment (glove boxes); isolation and drying on filter dryer; purification on 2000 litres; low/medium pressure columns (up to 9 bars); and two 2500 litre glasslined reactors. For hydrogenation, Indena has recently acquired a Biazzi hydrogenator, able to work up to 10 barg. Another point of strength for Indena as far as the production plant is concerned is the LK2 plant at the Settala site. Started in 2024, the kilolab LK2 has been further enhanced with equipment that allows Indena to work with highly potent molecules, guaranteeing an OEL of 1 ng/m³. This is a significant development, considering that the previous containment level for highly potent compounds was 20 ng/m³. After the addition of a small freeze dryer in the LK2 plant, already operational for the lyophilisation of HPAPIs guaranteeing an OEL of 1 ng/m³, the next project involves the installation of a larger-scale commercial freeze-drying line in 2026. Looking ahead, two further production lines will be added, always designed for research and processing of highly potent molecules. The first, which will be operational in 2026, will have a 65 litre reactor and a 100 litre reactor, both inserted inside glove boxes, and a 40 cm diameter filter dryer in Hastelloy C22. This configuration allows for filtration and drying under dynamic conditions, and the new equipment integrates with the existing systems in the plant. A second production line includes a freeze dryer with a capacity of 10 kg of ice in 24 hours, also located inside a glove box. This line will be equipped with a spray dryer inside the glove boxes, which will allow work on HPAPIs, guaranteeing an OEL of less than 1 ng/m³. Indena’s most recent expansion program also includes the construction of a state-of-the-art new 400 sq m R&D laboratory equipped with high performance and high containment fumehoods (12 bench-top fumehoods and two walk-in fumehoods), one laminar flow fumehood and two gloveboxes able to host the large team of scientists working at Indena. A new industrial GMP line with reactors up to 10.000 L will allow the company to produce and commercialise many higher volume APIs and HPAPIs. Moreover, Indena has a fermentation department for carrying out living cells-based biotransformation or secondary metabolite production, which can be exploited for the in-house production of toxins used in ADCs payload, guaranteeing an integrated and independent supply chain. Indena masters GMP microbial fermentation and biotransformation, and thanks to the availability of high containment lines for the downstream phase, it is the ideal partner for precision fermentation HPAPI development. The market for HPAPIs is actually growing due to the increasing prevalence of complex diseases and the development of targeted therapies. It has been estimated that HPAPIs may now account for more than 30% of the drug development pipeline. Some
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