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CDMO services are a key area of Indena’s expertise since 1990s. For the company it means not only Custom Development & Manufacturing Organization but also Curiosity for science, Development of knowledge, Mastering complexity, Obsession for quality.
In CDMO services, Indena acts as a strategic partner, going beyond the mere client/supplier relationship, with full commitment to developing new HPAPIs and APIs, from early clinical stages to commercial-scale manufacturing. 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 industrialization.
Indena’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 semisynthetic steps and for total-synthetic molecules. As a highly reliable Western European API producer, Indena displays a key uniqueness on Highly Potent APIs down to 20ng/m3 OEL, irrespective of their source, for which Indena is highly skilled and well equipped.
This expertise includes payloads for ADCs, with a backward integration on fermentation for toxins requiring this step and freeze-drying ability in high containment.
Nowadays Indena manufactures 10 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.
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.
Indena has been continually investing in know-how, personnel and equipment for its CDMO services for many years. Its most recent expansion program includes the construction of a state-of-the-art new 400 sqm R&D laboratory equipped with high performances and high containment fumehoods (12 bench-top fumehoods and 2 walk-in fumehoods), 1 laminar flow fumehood, 2 gloveboxes able to host 15 R&D scientists, completing the team of 70 scientists working at Indena.
Moreover, a new industrial GMP line with reactors until 10 000L will allow the company to produce and commercialize many more regular APIs and HPAPIs.
The challenges of a growing market and the importance of ADCs
The market for HPAPIs is 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, autoimmune disorders, infectious diseases and rare diseases.
And Indena is at the forefront in addressing the last 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 ambitions is to extend its expertise also to ADCs, Antibody drug conjugates, 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.
Indena is now able to manufacture linker-payload, that means specifically:
- Development & Clinical Supply batches: payload-linker process development, scale-up, analytical development, preliminary non GMP Bioconjugation trials.
Scale: from 10 mg to 100g. - GMP Manufacturing: payload-linker clinical manufacturing and commercial manufacturing. Scale: from 50 g to 5 kg.
- Outstanding analytical development capability
Indena is already present on the market with some payloads, as:
- Maytansinoids – DM1 & DM4 entirely manufactured in Europe at the Indena plant (including fermentation and synthesis steps)
- CDMO Payload-Linker: Manufacturing of a GMP Payload-Linker in phase 1
- Bioconjugation: ADC pre-clinical research – Bioconjugation trials.
The most recent state-of-the-art equipment implementation
Since 2019, Indena’s main production site is equipped with a GMP Pilot plant which includes 2 x 1000 L reactors in stainless steel, 400 and 1000 L glass lined reactors, 250 L hastelloy reactor, temperature ranges:
-80 °C/+200 °C, 500 L chromatographic column and hastelloy centrifuge.
The P8 plant is being expanded in some steps, starting from a first revamping in early 2024, then with further upgrades within end 2024/beginning of 2025. This expansion will allow the plant to enlarge the capacity of reactions/ chemical synthesis up to 10 times the actual capacity, produce on larger scale HPAPIs obtained both by synthesis and purification (small molecules to OEB5), higher production capacity for products actually made in other departments.
More technologies will be 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 low/medium pressure columns (up to 9 bars). For hydrogenation, we have recently acquired a Biazzi hydrogenator, able to work up to 10 barg.
The importance of People
One of the most important factor 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 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.
Indena is also well supported by a strong regulatory department that continuously interacts globally with the most important national health authorities, such as FDA, EMA, AIFA, ANSN, PDMA.
Sustainability: a concrete commitment, also for business continuity
Climate change is one of the most urgent sustainability challenges that people, governments and companies have to face.
Among the actions requested companies should take, is a responsible use of energy. Indena has always been oriented and committed to reducing fossil fuel consumption and use, saving energy, achieving high levels of energy self-production and implementing the use of renewable energy. That’s why Indena is equipping all its European sites with state-of-the-art photovoltaic panels: considering the actual equipments and the upcoming projects, the Indena Group will be equipped with over 4 MW of photovoltaic systems with a total estimated producibility of 4.000.000 kWh per year.
All of the Indena’s European factories are ISO 14001 Environmental Management System and ISO 45001 Occupational health and safety management system certified.
All the actions taken in favor of sustainability also enable Indena to be fully reliable in terms of business continuity. More specifically, Indena has the commitment to pursue the adaptation of the production system to EU policies regarding the fight against climate change.
Moreover, Indena has been awarded the ECOVADIS certification, which recognizes the company’s commitment to managing ESG risk and compliance.
