Custom Development & Manufacturing Organization services have been one of the key areas of Indena’s expertise since the 1990s. 

Leveraging its analytical and manufacturing capabilities, Indena positions its services in a niche to produce complex molecules having a very high value and requiring strong expertise for R&D, industrialization, high-containment handling and production of highly-potent active pharmaceutical ingredients (HPAPIs) from early stage to commercialization. 

Indena’s goal is to offer its customers the possibility of carrying out synthetic processes in a wide range of conditions for both natural molecules that require  semisynthetic steps and for total-synthetic molecules. The great differentiator as a reliable Western European producer is on HPAPIs produced down to 20 ng/m3 (Occupational Exposure Limit [OEL]), irrespective of their source, for which Indena is highly skilled and well equipped. 

Indena has been investing in expertise and equipment for its CDMO services for years. The most recent expansion program includes the construction of a brand-new R&D development laboratory of 400 m2 equipped with 12 fumehoods, 2 walk-in fumehoods, 1 laminar-flow fumehood, and 2 gloveboxes that will be able to host 15 R&D scientists.  

This laboratory has been built specifically to handle HPAPIs, and the project will be up and running by mid-2024. 

Indena first pioneering CDMO project 
Indena’s CDMO experience dates back many years, and the first project the company managed in this field was related to the first oncological blockbuster drug, paclitaxel. The challenge included the development of a sustainable supply chain for the ingredient, the development of a method of insulation under high-containment conditions, and the analytical methodology of control according to stringent pharmaceutical protocols in terms of purity and stability. 

During the development phase, the drug was extracted from the bark of the Pacific Yew Tree in a way that was not sustainable. To make the drug available on a commercial scale, the first challenge Indena had to face was to build a robust supply chain for the biomass, and this meant developing its own Yew Tree cultivations. The second challenge was related to the development of a strong industrial method to extract and purify the intermediate 10-deacetylbaccatin III.  

The third problem was the development of a robust and clean analytical frame for the project, complying with the most stringent regulations for pharmaceutical products. Moreover, Indena had also to develop its own synthetic methods to convert the intermediate 10-deacetylbaccatin III into the final API. 

The solution devised by Indena for paclitaxel was an extraordinary result as there were no alternatives for a real and sustainable production of the ingredient with the traditional method, from the bark of the Pacific Yew Tree. The solution found by Indena was the only one possible, and it has created a totally unique expertise: what Indena has learned in this experience of working with Nature has taught the company to manage complex molecules of any type, from both analytical and production perspectives. 

The success of its paclitaxel experience allowed the company to deeply change and enlarge its capacities and to face the market’s needs through a specific approach, which makes Indena a reliable partner for pharma and biotech companies’ success. 

The current CDMO scenario and Indena’s strategy and resources to face market needs 
As a matter of fact, the increasing number of oncology new chemical entities (NCEs) and antibody-drug conjugates, coupled with a growing focus on personalized medicine, is shaping the demand for CDMO services. The HPAPI market is undergoing a shift towards NCEs characterized by higher potency, growing molecular diversity, and segmentation for specific populations.  

As shown by its long story and expertise, and unlike newcomers in the field, Indena can provide an extensive know-how in safely handling HPAPIs, complemented by state-of-the-art equipment and installations.  

Within its long-term strategy, Indena has kept ahead of the curve by timely investing in specialized containment facilities that guarantee that both employees and the external environment are safe from exposure, capitalizing on more than 30 years of know-how in high containment. 

Nowadays, Indena manufactures 12 commercial HPAPIs: fully synthetic, semi-synthetic, and fermentation-based molecules. This area is now one of the core areas of expertise of the company. Each substance within Indena is assigned an Occupational Exposure Level (OEL) and allocated to the proper production line according to the required handling and containment rules. At its Settala facility in Italy, Indena can handle HPAPIs with an OEL from 1 mcg/m3 to 20 ng/m3

Moreover, Indena has a fermentation department to carry out living cells-based bio-transformation or secondary metabolites production. 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 fermentation-based HPAPI development. 

Indena’s CDMO services: the formula for clients’ success 
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. 

To always meet its clients’ expectations, Indena continues to invest, every year, in innovative technologies and services. The quality and efficiency of its equipment and facilities, however, are only half the story. 

At Indena, it’s well-understood that highly qualified, motivated, and trained technical staff, supported by a corporate culture that is strongly oriented to 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 interfaces with the most important national and worldwide health agencies such as AIFA, ANSN, FDA, and PDMA. 

The strengths of Indena’s CDMO are then supported by manufacturing-excellence programs, high standards of CDMO assets and qualified human resources. 

Sustainability: a concrete commitment, starting from energy management at Indena’s plants   
Climate change is one of the most urgent sustainability challenges that people, governments, and companies have to face, and this involves a responsible use of energy. Indena has always been oriented and committed to reducing fossil-fuel consumption and use, saving energy and achieving high levels of energy self-production.  

Such commitment is achieved mainly thanks to the company’s plant management, starting from its most important one, located at Settala near Milan in Italy, where Indena’s CDMO activities are implemented. 

Among the actions taken for the smart use of energy at the Settala site is a natural gas cogenerator plant, operational since 2016: it produces 16,566,000 kilowatt-hours per year, both electric and thermal energy, and enables a reduction of 1.699 Tons Equivalent Petrol (PET), which means a reduction of 2,500 Tons of CO2 emissions per year. 

Another important action for sustainability is the use of renewable energy, and Indena is equipping all its European sites with state-of-the-art photovoltaic panels.  

All the Indena’s European factories are certified ISO 14001 Environmental Management System and ISO 45001 Occupational Health and Safety Management System. 

All the actions taken in favor of sustainability also enable Indena to be fully reliable in terms of business continuity, and therefore to be a solid partner for all its clients.