IMA Active and Alfasigma: a passion for research and technological innovation

A sense of belonging, curiosity, passion and responsibility are just some of the values guiding Alfasigma, one of the 5 main players in Italy’s pharmaceutical industry, with sales of over a billion Euro in 2021. Alfasigma was first set up by Marino Golinelli in Bologna in 1948 and it is still firmly rooted in a long history of innovation and success: traditionally focused on medical prescription specialities, self-medication products and nutraceuticals, the company became a major player with its Contract Manufacturing division, manufacturing for other Italian and multinational pharmaceutical companies, which praise its level of quality and service. It follows a two-pronged business strategy:

• internally, a strong focus on research and development and manufacturing around certain proprietary molecules, which today account for over 50% of sales (Rifaximin, Sulodexide, Carnitine, L- methylfolate, Parnaparin);
• for external lines, a solid strategy of mergers and acquisitions with other Italian and international companies.

Founded in 2015 from the aggregation of the Alfa Wassermann and Sigma-Tau groups – two of Italy’s longest-standing pharmaceutical companies – the company acquired its current form in subsequent years by capitalising on the know-how, potential and specialisations of the companies it acquired and quickly became one of the main private players in the pharmaceutical sector. It now has branches and distributors in approximately 90 countries. The company has approximately 3,000 employees, half of whom are based in 5 premises in Italy: the business centre in Bologna and the international division headquarters in Milan, while its production facilities are located in Pomezia (RM), Alanno (PE) and Sermoneta (LT).
A few months ago, the Pomezia site inaugurated the new Labio 4.0, a multifunctional laboratory dedicated to the study of new formulations named after the founder Marino Golinelli. The new laboratories dedicated to pharmaceutical technology and analytical chemistry cover an area of 5,600 m2 and required an initial investment of over 17 million Euro.
“The inauguration of the new Labio 4.0 Marino Golinelli laboratory is part of the company’s strategy to invest more in research and development,” says Gabriele Petronio, Process Technology Development and Pilot Plant Manager at Alfasigma. “The new hub houses laboratories for developing innovative formulations, analytical chemistry labs and a new pilot plant, to which biotech and nanotech labs will be added at a later stage. The IMA Active technologies used at the new laboratory enable us to calibrate clinical and test batch production for new specialities in various oral forms (granular, coated and uncoated tablets, capsules, pellets/minitabs), allowing Alfasigma to stand out on the national and international stage when it comes to technological innovation and development.”

Such a comprehensive and structured plant certainly have been complex to design and build. What were your requirements?

Gabriele Petronio: “One of the key aspects of Labio 4.0 is that it can operate midway between the size of a technological development laboratory and the size of semi-industrial production, thereby speeding up the intermediate steps between the idea and its creation. The plant can also carry out mini-production runs with innovative pharmaceutical forms in Scale-Up and Scale-Down to optimise existing processes and better characterise those developed in tech labs prior to industrialisation, with consequent benefits for resources and timing. Finally, the laboratory can be used to produce small batches for clinical studies. All this called for an entire high-containment plant (OEB 4) with separate working centres that could operate at different pressures and keep the flow of personnel and the flow of material completely separate. In addition, since we have to operate at various scales of production, the same plant had to be capable of processing very different batches whilst being versatile and flexible: we do not know what product we will be working with in the future, so the laboratory had to be equipped to handle all possible oral forms. The collaboration with IMA Active enabled us to do all of this”.

How is the plant structured and what technologies does it use?

Gabriele Petronio: “The entire plant was built in containment from active ingredient dispensing with Bag Dumping Station (IMA, Italy) and powder mixing, which is done with the Cyclops Mini (IMA, Italy). Subsequently in the laboratory we can make tablets with the Prexima 80 tableting machine (IMA, Italy) suitable for small batches and R&D applications. The machine can be equipped with different punches depending on the product being processed while offering complete flexibility. If necessary, we can coat the tablets using the Perfima Lab (IMA, Italy) with a 30-litre perforated drum. This coating machine has a compact size and an interchangeable drum (from 3 to 70 litres), making it suitable for laboratory batches and small production batches. Perfima Lab guarantees maximum efficiency and precision thanks to the design of the drums and the positioning of the paddles. In addition to the perforated drum, the Perfima Lab is also equipped with a wedge wide screen drum for film coating of pellets and mini/micro-tablets and having flexibility over the different types of solid oral forms that can be made. In addition to tablets, we can also produce powder or pellet-filled capsules. The Zanasi 16 Plus capsule filling machine (IMA, Italy) has a very simple yet versatile configuration, enabling it to dose powders, pellets, tablets, mini/micro-tablets and liquids into the same capsule (including in several combinations). This capsule filling machine is extremely compact and easy to use and can dose different products with extreme precision and at high speeds. Furthermore, in a laboratory like Labio 4.0 it is important to be able to change configuration quickly, optimising the time needed to clean the machine.
Last but not least, we should highlight how the products are handled inside the laboratory. Since we often work with active products, it is essential to safeguard workers’ safety so that they never come into contact with the powders or products being handled. All the materials are handled and moved inside bins supplied by IMA, which are fitted with split valves that prevent product escaping. These bins are then lifted by Hercules columns (IMA, Italy) for loading the tablet press and capsule filling machine by gravity, once again preventing product leakage.
Finally, all supplied parts can be washed in complete safety thanks to the Hydrowash (IMA, Italy), which is designed to operate standalone inside or as a feeding group to wash other on-site machinery”.

What is the added value of the collaboration with IMA Active on this project?

Fabrizio Giorgi: “To be honest, IMA was not our immediate choice for this project. We certainly knew IMA and had worked with them several times, but initially we were looking at a number of competing candidates. When we came to the final decision, we chose IMA Active for three main reasons: IMA Active presented itself as a single and real one-stop-shop supplier. It could supply us all the machines we needed, teaming quality and versatility. As we have said, this laboratory is designed to be an R&D hub, so we cannot know now what product we will be working with in the future. IMA Active machines enable us to process different formats now and be able to work with others in the future with minimal adjustments (e.g. on the Zanasi capsule filling machine we will be able to fit other units in the future and fill powders and pellets in the same capsules). Secondly, the entire IMA Active team, from the sales staff to the technicians, have always demonstrated great skill and experience. Last but not least, the professionalism of the IMA technicians who helped us start up the plant and worked alongside our technologists to set up the machines. In short, the climate and relationship of trust created between us and IMA enabled this great project to be created.