As a strategic partner, Indena goes beyond the mere client/supplier relationship and is committed to developing new HPAPIs (down to 20 ng/m3 OEL) and APIs from the early clinical stages to commercial-scale manufacturing.
Leveraging its analytical, development and manufacturing capabilities, Indena offers added value when producing complex molecules. Indena helps its customers to optimise synthetic processes in a wide range of conditions for both naturally derived and chemical molecules.
This expertise includes payloads for ADCs, reverse integration, fermentation, freeze-drying and high-level containment.
Indena manufactures 10 commercial HPAPIs and 12 clinical phase ones (fully synthetic to fermentation-derived molecules). Each substance is assigned an Occupational Exposure Level and allocated to the proper production line according to the required handling and containment rules.
At its Settala facility, Indena can handle HPAPIs with an OEL as low as 1 ng/m3. Indena’s fermentation department can handle cell-based biotransformations or secondary metabolite production for the in-house production of toxins used in ADC payloads.
GMP capabilities are available thanks to the company’s high-level containment lines for downstream processing.
Indena has been investing in know-how, personnel and equipment for many years. Its most recent expansion includes the construction of a state-of-the-art 400 m2 R&D laboratory equipped with high performance/containment fume hoods and gloveboxes able to host 15 R&D scientists.
Furthermore, a new industrial GMP line with 10,000 L reactors will allow the company to produce and commercialise many more APIs and HPAPIs.
The challenges of a growing market and the importance of ADCs
Owing to the increasing prevalence of complex diseases and the development of targeted therapies, the HPAPI market is growing. HPAPIs now account for more than 30% of the drug development pipeline.
Indena is at the forefront when it comes to addressing current market challenges as its HPAPI production derives from more than 30 years of experience and the first oncological blockbuster: Paclitaxel.
Producing Paclitaxel was challenging; issues included developing a sustainable supply chain, ensuring isolation under high-containment conditions and implementing an analytical control methodology to meet the stringent purity and stability protocols.
Indena’s solution for Paclitaxel was an extraordinary result and created a unique proficiency within the company.
Based on its experience of working with nature, Indena has learned to manage — both analytically and production-wise — complex molecules of any type.
Today, Indena’s ambitions also extend to ADCs (antibody drug conjugates), which represent a significant advancement in targeted therapy and holds 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-payloads and provide services such as
- development and clinical supply batches: payload-linker process development, scale-up, analytical development, preliminary non-GMP bioconjugation trials
- GMP manufacturing: payload-linker clinical and commercial production (from 50 g to 5 kg)
- outstanding analytical development capability
- scale: from 10 mg to 100 g
Indena is already present on the market with certain payloads
- Maytansinoids: DM1 and DM4 manufactured at the Indena plant (including fermentation and synthesis)
- CDMO payload-linker: production of a GMP payload-linker in Phase I
- bioconjugation: ADC preclinical research (bioconjugation trials).
Recent state-of-the-art equipment implementation
Since 2019, Indena’s main production site has been equipped with a GMP pilot plant that includes 2 x 1000 L stainless steel reactors, 400 and 1000 L glass-lined reactors, a 250 L Hastelloy reactor, a 500 L chromatographic column and a Hastelloy centrifuge.
The P8 plant is being expanded, which will enable the facility to handle reactions/syntheses up to 10 times the actual capacity, produce larger volumes of HPAPIs (small molecules to OEB5) and offer higher production capacities for products made in other departments.
In addition, more technologies will be added for the chemical synthesis and purification of APIs/HPAPIs, including contained centrifugation and reactor loading (glove boxes), isolation, filter dryer, purification and hydrogenation.
The importance of people
In terms of providing quality CDMO services, a key factor for Indena is its people. This means the human and professional resources of everyone involved, where lifelong professional experience is fused with the enthusiasm and fresh skills of many young scientists.
Indena understands that highly qualified, motivated and trained technical staff, supported by a corporate culture that’s 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 with the most important national health authorities, such as FDA, EMA, AIFA, ANSN and PDMA.
Sustainability: a firm commitment for the environment and for business continuity
Climate change is one of the most urgent sustainability challenges that people, governments and companies alike must face.
Key to addressing this is the responsible use of energy. Indena has always been oriented and committed to reducing fossil fuel consumption and use, saving energy, achieving high levels of 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. In fact, the Indena Group will implement more than 4 MW of photovoltaic systems with a total estimated output of 4,000,000 kWh per year.
In addition, all Indena’s European factories are ISO 14001 Environmental Management System and ISO 45001 Occupational Health and Safety Management System certified. All our sustainability initiatives enable Indena to be fully reliable in terms of business continuity.
More specifically, Indena is committed to adopting the EU policies regarding the fight against climate change.
The company’s first goals — and related investments — are better energy efficiency, the more effective use of resources and a fundamental change in its overall production process that allows greater energy or resource efficiency.
The programme includes the following implementations:
- for energy efficiency: a high-performance (–2 °C) chiller, efficient nitrogen production system, high-efficiency heat pumps
- for heat and water efficiency: 7–12 °C high-efficiency chiller
- for renewable energy: an additional 1.5 MW solar photovoltaic power plant.
The attention paid by Indena to the goals of business continuity, risk mitigation, the development of a dedicated plan, the capability to resume operations in a timely manner and the protection of critical assets (including data, personnel and technology) makes Indena a totally reliable partner for all its clients.
Moreover, Indena has been awarded Bronze Medal ECOVADIS certification.
ECOVADIS recognises the company’s commitment to managing ESG risk and compliance, achieve corporate sustainability goals and drive large-scale impact by fostering improved sustainability performance for the company and its value chain.
