Flagship project for Bio-S strategy

Flagship project for Bio-S strategy

The French pharmaceutical company Servier is expanding its business model. As it moves towards becoming a recognized player in oncology, as part of its BIO-S strategy it is investing in production capacities for biologics and small molecules. The greatest degree of flexibility possible is ensured by a MultiUse line that can fill injectable solutions into syringes and vials. Servier opted for a complete system including a high-potent isolator and freeze dryer, the likes of which only Optima can supply.
'Les Laboratoires Servier Industrie' operates worldwide, employing 22,500 workers. The pharmaceutical company has historically had a strong presence in treating cardiovascular diseases, and it reinvests over 20 percent of its sales in research and development. The Servier Group has an exceptional manufacturing strategy, with a network of 16 production sites. 98 percent of its active ingredients are produced in France.
Even with its current expansion of its strategic direction into oncology the French pharmaceutical firm is sticking to this line. Servier has also expanded its oncology and hematology pipeline by making several acquisitions: Shire, Ireland's oncology business in 2018, and Symphogen, Denmark, in 2020 and Agios, USA in spring 2021 In Gidy, around 15 km north of the city of Orléans, Servier operates its largest factory with three manufacturing facilities.
One of these has been under conversion since 2018: In the future, the production facility known as Bio-S will be producing monoclonal antibodies for preclinical and clinical phases for cancer treatments, among other things. Servier's first biopharmaceutical manufacturing facility is scheduled to start operating in 2023.
The development of its capacity for the biotechnological production of living cells is not the only challenge facing the manufacturer, which so far has focused on solid forms of drug administration. The filling of the new drugs in the future also poses different requirements than in the past, because they are intended for injection. Christophe Aussourd, Head of Pharmaceutical Industrial Development explained: "We wanted a flexible production line to meet initial clinical needs for biologicals and small molecules, as well as potential commercial manufacturing in the future." As early as 2016, Servier was putting out feelers for suitable suppliers. Fortunately, Optima's name was by no means unfamiliar to some Servier employees with expertise in biologicals production.
MultiUse line
The MultiUse line enables Servier to flexibly fill syringes, cartridges and vials with biopharmaceutical drugs.
The French pharmaceutical company Servier is expanding its business model. As it moves towards becoming a recognized player in oncology, as part of its BIO-S strategy it is investing in production capacities for biologics and small molecules. The greatest degree of flexibility possible is ensured by a MultiUse line that can fill injectable solutions into syringes and vials. Servier opted for a complete system including a high-potent isolator and freeze dryer, the likes of which only Optima can supply.
'Les Laboratoires Servier Industrie' operates worldwide, employing 22,500 workers. The pharmaceutical company has historically had a strong presence in treating cardiovascular diseases, and it reinvests over 20 percent of its sales in research and development. The Servier Group has an exceptional manufacturing strategy, with a network of 16 production sites. 98 percent of its active ingredients are produced in France.
Even with its current expansion of its strategic direction into oncology the French pharmaceutical firm is sticking to this line. Servier has also expanded its oncology and hematology pipeline by making several acquisitions: Shire, Ireland's oncology business in 2018, and Symphogen, Denmark, in 2020 and Agios, USA in spring 2021 In Gidy, around 15 km north of the city of Orléans, Servier operates its largest factory with three manufacturing facilities.
One of these has been under conversion since 2018: In the future, the production facility known as Bio-S will be producing monoclonal antibodies for preclinical and clinical phases for cancer treatments, among other things. Servier's first biopharmaceutical manufacturing facility is scheduled to start operating in 2023.
The development of its capacity for the biotechnological production of living cells is not the only challenge facing the manufacturer, which so far has focused on solid forms of drug administration. The filling of the new drugs in the future also poses different requirements than in the past, because they are intended for injection. Christophe Aussourd, Head of Pharmaceutical Industrial Development explained: "We wanted a flexible production line to meet initial clinical needs for biologicals and small molecules, as well as potential commercial manufacturing in the future." As early as 2016, Servier was putting out feelers for suitable suppliers. Fortunately, Optima's name was by no means unfamiliar to some Servier employees with expertise in biologicals production.
MultiUse line
The MultiUse line enables Servier to flexibly fill syringes, cartridges and vials with biopharmaceutical drugs.
Turnkey thinking – the key to success
turnkey project
This turnkey project, which combined the MultiUse line with the freeze dryer and isolator, called for close coordination between Optima's different units.
This set the scene for Optima's flagship project for the French market. The OPTIMA MultiUse line for highly active ingredients, implemented as a turnkey project with filling line, high-potent isolator, and freeze dryer from a single source, was to be the first of its kind in France. First, it was necessary to build trust. Fabrice Escourrou, Sales Manager Optima Pharma France, reports: "A lot of Servier employees were involved in the project, including quite a few who did not know us at all. After the project participants visited us in Schwaebisch Hall, we were able to convince them that we offer the right, innovative technologies from a single source. It was very important for Servier executives to have a single point of contact for the entire line."
Christophe Aussourd says: "After an objective comparison of the offers from several competitors, we decided to go with Optima's solution. Besides the criteria of the integrated design and project management of the filling system, high-potent isolator and freeze dryer, we were convinced by the state-of-the-art technology of the flexible line and its '4.0 compliance'. Lastly, the spirit of partnership in terms of technical communication was also a decisive factor."
Turnkey thinking – the key to success
This set the scene for Optima's flagship project for the French market. The OPTIMA MultiUse line for highly active ingredients, implemented as a turnkey project with filling line, high-potent isolator, and freeze dryer from a single source, was to be the first of its kind in France. First, it was necessary to build trust. Fabrice Escourrou, Sales Manager Optima Pharma France, reports: "A lot of Servier employees were involved in the project, including quite a few who did not know us at all. After the project participants visited us in Schwaebisch Hall, we were able to convince them that we offer the right, innovative technologies from a single source. It was very important for Servier executives to have a single point of contact for the entire line."
Christophe Aussourd says: "After an objective comparison of the offers from several competitors, we decided to go with Optima's solution. Besides the criteria of the integrated design and project management of the filling system, high-potent isolator and freeze dryer, we were convinced by the state-of-the-art technology of the flexible line and its '4.0 compliance'. Lastly, the spirit of partnership in terms of technical communication was also a decisive factor."
turnkey project
This turnkey project, which combined the MultiUse line with the freeze dryer and isolator, called for close coordination between Optima's different units.

"Besides the criteria of the integrated design and project management of the filling system, high-potent isolator and freeze dryer, we were convinced by the state-of-the-art technology of the flexible line and its '4.0 compliance'. "
Christophe Assourd, Head of Pharmaceutical Industrial Development at Servier

Factory Acceptance Test
An important intermediate step on the path to an integrated line: The freeze dryer Factory Acceptance Test at Optima Pharma's Mornshausen site already took place in September 2020, in compliance with the COVID-19 regulations.
Optima Pharma has demonstrated its high level of expertise by designing the line as a MultiUse filling and closing line for syringes, cartridges and vials associated with high potency products. Rainer Goeller, who was responsible for the project planning of the filling system, remembers: "During the project planning phase, it quickly became clear that Servier was looking for a very compact system. We therefore scrapped an initial L-shaped layout and designed the system made up of a filling line and freeze dryer in a linear configuration. Rachid Azzouzi, F & F Workshop Manager says that he is satisfied with the project work: "We were involved at every stage of the project, particularly during the mock-up and design phases, to fine-tune the technical solutions that Optima proposed such as the pick-and-place technology and the filler set definition."
Factory Acceptance Test
An important intermediate step on the path to an integrated line: The freeze dryer Factory Acceptance Test at Optima Pharma's Mornshausen site already took place in September 2020, in compliance with the COVID-19 regulations.
Optima Pharma has demonstrated its high level of expertise by designing the line as a MultiUse filling and closing line for syringes, cartridges and vials associated with high potency products. Rainer Goeller, who was responsible for the project planning of the filling system, remembers: "During the project planning phase, it quickly became clear that Servier was looking for a very compact system. We therefore scrapped an initial L-shaped layout and designed the system made up of a filling line and freeze dryer in a linear configuration. Rachid Azzouzi, F & F Workshop Manager says that he is satisfied with the project work: "We were involved at every stage of the project, particularly during the mock-up and design phases, to fine-tune the technical solutions that Optima proposed such as the pick-and-place technology and the filler set definition."
Maximum yield for high-value products
Servier's aim was not to achieve a high output, but rather the highest possible product yield. The Servier MultiUse line fills up to 3,000 containers per hour. All packaging materials are supplied pre-nested and pre-sterilized. Once the containers have been unpacked, partly manually and partly semi-automatically, and the protective slide has been removed by the Tyvek-Removal robot, they are separated and filled. 100% in-process control and, where necessary, refilling minimizes product loss. The Servier line uses peristaltic pumps for filling. They only introduce low shear forces, which is especially important for biological products. When there is a product changeover, the single-use product path coming into contact with the liquid can be easily replaced. There is no need for time-consuming cleaning and sterilization of this unit. After filling, the syringes and cartridges are closed and derived. In contrast, vials can be freeze-dried in the next step. When designing this process, the requirements were precisely taken into account. The Optima team pays strict attention to every detail that can affect careful lyophilization.
freeze dryer
The integrated freeze dryer is accompanied by an automatic loading and unloading system that slides the vials into the freeze dryer row by row. The vials are separated again during unloading.
Tyvek Removal Robot
The Tyvek Removal Robot removes the sealed film from the nest before separating the containers inside.
Harald Galonska, the lead Project Engineering Manager, explains: "For example, the size of the intermediate valve between the drying chamber and the condenser must be right. This is the only way that any water vapor that is generated can be removed quickly enough." Otherwise, the entire batch could thaw, making it unusable. For high-value biotech products such as the ones to be produced by Servier in the future, this would mean a loss of multiples of €100,000. So Galonska basically asks what the worst-case scenarios would be. He describes: "The compact Servier GT C-4 freeze dryer is designed to be usable for all products with the shortest possible process times."
Maximum yield for high-value products
Servier's aim was not to achieve a high output, but rather the highest possible product yield. The Servier MultiUse line fills up to 3,000 containers per hour. All packaging materials are supplied pre-nested and pre-sterilized. Once the containers have been unpacked, partly manually and partly semi-automatically, and the protective slide has been removed by the Tyvek-Removal robot, they are separated and filled. 100% in-process control and, where necessary, refilling minimizes product loss. The Servier line uses peristaltic pumps for filling. They only introduce low shear forces, which is especially important for biological products. When there is a product changeover, the single-use product path coming into contact with the liquid can be easily replaced. There is no need for time-consuming cleaning and sterilization of this unit. After filling, the syringes and cartridges are closed and derived. In contrast, vials can be freeze-dried in the next step. When designing this process, the requirements were precisely taken into account. The Optima team pays strict attention to every detail that can affect careful lyophilization.
freeze dryer
The integrated freeze dryer is accompanied by an automatic loading and unloading system that slides the vials into the freeze dryer row by row. The vials are separated again during unloading.
Tyvek Removal Robot
The Tyvek Removal Robot removes the sealed film from the nest before separating the containers inside.
Harald Galonska, the lead Project Engineering Manager, explains: "For example, the size of the intermediate valve between the drying chamber and the condenser must be right. This is the only way that any water vapor that is generated can be removed quickly enough." Otherwise, the entire batch could thaw, making it unusable. For high-value biotech products such as the ones to be produced by Servier in the future, this would mean a loss of multiples of €100,000. So Galonska basically asks what the worst-case scenarios would be. He describes: "The compact Servier GT C-4 freeze dryer is designed to be usable for all products with the shortest possible process times."
The inclusion of the freeze dryer in an integrated line design requires close internal coordination in terms of design, documentation and time scheduling. "We deliver the majority of the freeze dryers as part of turnkey projects, so we are experienced in doing this," says Dominic Reeh, who was the Project Manager responsible for the freeze dryer. The entire plant is controlled centrally via a line SCADA. In addition, Servier was looking for integration with its higher-level systems. Franck Durtchi, Automation Manager at Servier explains: "Our 4.0 Servier Bio-S working group designed the requirements to ensure the MultiUse line, freeze dryer and isolator communicate with the Bio-S facility. Our goal is to manage electronic batch records via our MES (Manufacturing Execution System). To do this, product and environmental data will be collected, logged and analyzed."

"The system's flexibility provides real added value."
Luc-André Claustres, Head of F & F and Project Manager at Servier

Luc-André Claustres, Head of F & F and Project Manager at Servier sums up: "We are very satisfied with the project management. A collaborative and user-focused mindset was its key feature.” In early March 2021, the freeze dryer, isolator and MultiUse filling line were delivered to Servier's Bio-S plant. "The system's flexibility provides real added value", says Luc-André Claustres, praising the system. "Thanks to its ability to handle both different types of containers and different kinds of pharmaceuticals, whether they are high-potent or not, liquid or freeze-dried, biologics or small molecules, we will be able to meet the needs of our clinical products going forward." He also feels that the automatic loading and unloading system for vials and the quick switchover of the format parts without the need for tools are a major advantage. This has made the state-of-the-art line an important factor in making Servier's Bio-S project a success.
Information
IMPORTANT FOR YOU
  • The OPTIMA MultiUse line, including the high-potent isolator and freeze dryer, completes the first Servier Bio-S biotech production facility in Gidy, France.

  • The flexible line for vials, syringes and cartridges will fulfill the initial clinical demand for biologicals and small molecules in the future.

  • The 100% weight control ensures high yield for the high value products.

  • The dimensions of the integrated freeze dryer are such that it can be operated with the shortest possible processing times.

  • The integration of the line SCADA into the higher-level IT enables Servier to manage electronic batch records via the in-house MES.

  This report has been published in the O-COM Magazin Pharma July | 2021.

With kind permission of Servier

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