The Huningue site is also the oldest biomedicine factory in France. It was the Swiss chemist Ciba, whose origins date back to the end of the 19th century and the birth of the chemical dye industry, which launched its construction in 1994, two years before merging with Sandoz to create the pharmaceutical giant Novartis. “Ciba was visionary and invested at risk, well in advance, in this field of monoclonal antibodies», relates Imre Bajusz, director of the Huningue site. He even says that the factory found itself “completely shut down for four years» in the early years, but was ready when Novartis’ first biotechnology drugs came into production. He then speaks “of an explosion, with a first industrial transfer in 2002, the first commercial batches in 2005, then a second product from 2007».
Four biomedicines
Today, four drugs are produced within the three installed production lines, with multiple indications such as severe asthma, psoriasis, kidney transplant rejection, and even rare autoimmune diseases. Before the gigantism of 15,000 liter bioreactors, everything started on a much more modest scale. The process begins in a clean room with extremely secure access. Loïc Millot, production manager, explains that it all begins “with ampoules of a few milliliters from the Novartis cell bank and containing modified mammalian cells. They are thawed and added to a culture medium for cell amplification».
In the Alsatian Novartis factory, the first cells obtained are about to start a long process during which they will continue to multiply in increasingly large bioreactors. © Como Sittler
This phase is one of the only two moments when operators are in direct contact with the product, which requires drastic cleanliness requirements, with very strict protective equipment and a real dressing and decontamination ritual. For around ten days, these cells will multiply in their culture media, knowing that a cell divides in 24 hours. They emerge from this first stage in a spinner, a sort of jar with a capacity of approximately three liters, in the form of a pink-orange solution. From there follows a journey through several ever larger bioreactors, from 25 to 2500 liters before the big plunge into a 15,000 liter, in ever fresher and more imposing culture media to nourish and multiply these cells.
10 to 15 million euros invested per year for maintenance and equipment
In Huningue, as in other monoclonal antibody factories, you have to be patient. “It’s slower than with chemical production», underlines Imre Bajusz. It is also very delicate, therefore very expensive. Manufacturing a batch can take several months in total, and any failure in the configuration can lead to very large invoices. Every year, Novartis invests “between 10 and 15 million euros» for the maintenance and equipment of the factory to guarantee the best production conditions, notes the site director.
From the top of the 15,000 liter bioreactors, all parameters are constantly monitored via strong digitalization of the equipment. © Como Sittler
These cultured cells are not used as such in the medicine. After their journey, they arrive in the largest bioreactors where, after a few days, “we will generate stress – which is not necessarily negative in the biological sense – such as the addition of ingredients, the change of certain parameters, such as temperature or pH, which will modify the behavior of the cells», explains Loïc Millot. These changes in conditions stop cell division and transform cells into mini-factories. They then take action to express the protein of interest sought, and thus produce, biologically, the active principle of the future biomedicine.
The final stages of manufacturing take place with purification phases, with chromatography and filtration stages to retain only the active ingredient, before filling into sterile bags then freezing before shipping to secondary production sites for drug formulation and packaging.
After the filtration and purification steps, the batches of monoclonal antibodies are fractionated in sterile bags before being frozen and sent to drug formulation and packaging. © Como Sittler
Novartis continues to invest in Huningue but restructures at the same time for its competitiveness
Over the last three years, Novartis has invested around 500 million euros in France, both in production, primarily for this Huningue site, and in R&D – the Swiss laboratory has nearly 2,000 employees in the region. In the Alsatian factory, since 2019, the group has for example added a third chromatography line and a second production unit, equipped with two lines, commissioned in 2020.
A new 30 million euro project is also being studied, in the field of vectorized internal radiotherapy. This segment of nuclear medicine consists of bringing a radioactive element directly into the body to tumor cells to irradiate and eradicate them. Today, Novartis is the only laboratory in the world to have two drugs of this type on this market, highly coveted by the French Orano Med in particular.
This project, which has not yet been approved, would represent a growth driver for the Huningue site, which must also work on its competitiveness. Currently, a reorganization is being studied and could lead to the elimination of up to 50 positions, out of the 700 listed today. Novartis is currently counting on voluntary departures, but not before the end of 2025, management says, while retirements will not be replaced.
