Indena is a highly reliable Western European API producer, displaying a key uniqueness on HPAPIs down to 1ng/m3 OEL.
Since the 1990s, Indena has acted as a strategic partner in CDMO services, going beyond the mere client-supplier relationship, with full commitment to developing new HPAPIs and APIs, from early clinical stages to commercial-scale manufacturing.
Indena’s technological and research capacity, together, represents a unique and distinctive case in the CDMO operator sector. Its leadership and excellence in custom services lie in its commitment to continuously investing in new and updated equipment and technologies, as well as on talented researchers.
The company’s goal is to offer its customers the possibility of carrying out synthetic processes in a wide range of conditions, both for naturally-derived molecules (from botanical sources or from microbial fermentation) requiring semi-synthetic steps and for total-synthetic molecules. Leveraging on its analytical, development and manufacturing capabilities, Indena positions its services in a high added value segment, producing complex molecules requiring both leading technologies and significant expertise in R&D and industrialisation. As a highly reliable Western European API producer, Indena displays a key uniqueness on Highly Potent APIs down to 1ng/m3 OEL, irrespective of their source, for which Indena is highly skilled and well-equipped.
Nowadays, Indena manufactures ten commercial HPAPIs and 12 clinical phase HPAPIs: fully synthetic, semi-synthetic and fermentation molecules. This is now one of the company’s core areas of expertise. Each substance within Indena is assigned an Occupational Exposure Level and allocated to the proper production line according to the required handling and containment rules. At the Settala facility, Indena can handle HPAPIs with an OEL starting from 1 ng/m3. Indena’s expertise includes payloads for Antibody Drug Conjugates (ADCs), with a backward integration on fermentation for toxins requiring this step and freeze-drying ability in high containment.
As for the equipment, since 2019 in Indena’s main production site is a GMP plant that can handle a wide range of synthetic reactions within a temperature ranges of -80 °C/+150 °C. The plant includes two 1000 L reactors in stainless steel, 400 and 1000 L glass lined reactors, 250 L hastelloy reactor, 500 L chromatographic column and a hastelloy centrifuge, and can be also used for small-scale commercial productions.
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 glass-lined 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 bio-transformation 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 bio-transformation, 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 of the conditions that use HPAPIs include: cancers, auto-immune disorders, infectious diseases and rare diseases.
In addition, Indena is at the forefront in addressing the latest market challenges, as its capability in HPAPIs production comes from the experience done more than 30 years ago with the first oncological blockbuster drug, Paclitaxel.
The production of Paclitaxel involved some challenges: the development of a sustainable supply chain for the ingredient; the development of a method of isolation under high-containment conditions; and the analytical methodology of control according to stringent pharmaceutical protocols in terms of purity and stability. The solution devised by Indena for Paclitaxel was an extraordinary result and created a unique expertise of the company – from its experience of working with nature, Indena has learned to manage complex molecules of any type, from both the analytical and the production perspectives.
Today, Indena’s ambition is to extend its expertise to ADCs, which represent a significant advancement in targeted therapy, holding immense promise for the pharmaceutical industry. These engineered molecules combine the specificity of monoclonal antibodies with the potent cytotoxicity of chemotherapeutic drugs, offering a more precise and potentially less toxic approach.
One of the most important factors for the quality of the CDMO services delivered by Indena is people. It means the human and professional resources of the whole teams working on CDMO activities, where lifelong professional experiences are fused with the enthusiasm and fresh skills of many young scientists.
Because at Indena it is well-known that highly qualified, motivated and trained technical staff, supported by a corporate culture, strongly oriented toward quality and rigorous HSE policies, is essential to ensure that operations run safely, seamlessly and efficiently.
