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Seamless transition from development to GMP sterile production and lyophilization: Thisrequires a sophisticated concept with precisely coordinated systems and the necessary expertise. To achieve this, CDMO ten23 health has invested in MultiUse systems and a LYO-SCALE pilot freeze dryer from Optima. This unique project includes high-tech features and sustainability as major focus points.
CDMO ten23 health’s sterile production facility is in the heart of Valais, in Visp, Switzerland. Three Optima lines will be in operation at this location. “Line 1” is a single-laned MultiUse system, which has been in operation since 2018. It is used for GMP-compliant manufacturing of clinical and commercial products and is capable of processing vials, cartridges, and pre-filled syringes in RTU (ready-to-use) format.
The next phase is “Line 2” – an 8-laned MultiUse system that, like “Line 1”, can handle all three RTU container types: Pre-filled syringes, cartridges, and vials. “Line 3” will be a dedicated vial line, integrated in-line with two freeze dryers. This line will expand ten23 health’s sterile manufacturing capabilities starting in 2026. All three lines are isolator-based and fully compliant with Annex 1 requirements. In addition to manufacturing, the Visp site is also home to ten23 health’s microbiology quality control laboratory.
In Basel, the second site of ten23 health in Switzerland, the company offers comprehensive services across the entire drug development and manufacturing spectrum. This includes formulation development, testing of primary packaging materials, definition of parameters for fill-and-finish processes, as well as final quality control and stability testing.
A milestone for the industry is the unprecedented level of detail in parameter development for sterile filling and lyophilization during the process development for sterile drug products. Achieving this level of precision requires meeting extensive and exact requirements – a challenge that ultimately led to the development of a fourth system in collaboration with Optima, now operated at the Basel site.
This specialized pilot system known as "Line 0" at ten23 health, includes a MultiUse LAB and an integrated LYO-SCALE pilot freeze dryer. What sets this system apart is that it serves as a scaled-down replica of ten23 health’s larger production lines. All core functions, of which there are many in multi-use systems, are mirrored at the pilot scale, enabling development studies. This fourth line was installed beginning of 2025.
The pilot plant, operated under ISO 9001 standards, is housed in rooms equipped with ceiling-mounted laminar flow systems. While not built to GMP specifications, the environment is designed to minimize potential contamination risks during development activities. To support this, both the MultiUse LAB and the semi-automatic freeze dryer loading system are enclosed with machine housings that extend to the ceiling. To replicate production-like conditions with minimal particle presence, ten23 health commissioned smoke studies and airflow simulations at Optima.
This is essential because primary packaging components must be compatible with the formulation; their interaction can significantly impact product stability. Long-term stability, container closure integrity, and overall product quality can only be ensured through the optimized combination of formulation, packaging, and manufacturing processes. To support this, ten23 health uses its pilot system to produce early, representative batches for stability studies to provide valuable long-term stability data.
As a result, "Line 0" can be used not only for development work but also for producing material for preclinical studies, stability testing, analytical reference standards, and evaluating new primary packaging material or stoppering processes. This pilot facility is highly representative of GMP production conditions in Visp – a significant distinction from typical laboratory setups.
With the new ‘Line 0’, we ensure that our processes are as transferable as possible to GMP production.
Freeze-drying processes are typically lengthy, often taking many hours or even days during which production-scale freeze dryers would be occupied. Traditionally, formulation development in laboratory settings was limited, as substantial adjustments were often required when scaling up to production equipment. In freeze-drying development, it is not only the absolute values for temperature and vacuum that matter; drug-specific progression curves must also be precisely defined.
The pilot freeze dryer delivers significant time and efficiency gains, especially when the developed parameters can be accurately transferred to full-scale production. Beyond time savings, the new pilot system also enables substantial reductions in energy consumption, drug substance usage, and other costly materials.
Processes such as dosing and closing often perceived as straightforward, can be just as complex as freeze-drying. Here too, parameters must be tailored to the specific properties of each drug product. For instance, shear-sensitive active ingredients or highly concentrated, viscous formulations place particularly high demands on dosing systems. Achieving high filling accuracy, especially with small volumes, is essential, and must often be balanced with specific throughput requirements.
A well-known challenge is the formation of minute air bubbles, particularly around the needle tip of pre-filled syringes after dosing. Even tiny air pockets, which may not be visible immediately after closing, can accumulate over time into clearly detectable bubbles. To prevent this, vacuum-assisted processes are employed, ensuring product integrity and consistent visual quality.
This leads to stability studies. During development, it must be determined whether a drug product can be stored over extended periods while maintaining its efficacy, safety, and overall quality, including sterility. Drug formulations, which combine active ingredients with excipients, are typically developed during preclinical phases. At this stage, filling and closing processes are often conducted under non-GMP conditions.
This is essential because primary packaging components must be compatible with the formulation; their interaction can significantly impact product stability. Long-term stability, container closure integrity, and overall product quality can only be ensured through the optimized combination of formulation, packaging, and manufacturing processes. To support this, ten23 health uses its pilot system to produce early, representative batches for stability studies to provide valuable long-term stability data.
Prof. Dr. Mahler: “Conducting studies and tests on our production equipment would not only slow down manufacturing timelines - the necessary preparation and follow-up are also highly time-consuming. With our fully equipped pilot system, we eliminate these constraints,” explains Mahler. He adds, “The immediate and convenient access to the pilot system is another significant advantage.”
Extensive development work in the non-GMP “Line 0” manufacturing area, combined with expertise, lays the foundation for filling, closing, and freeze-drying processes in GMP production. The MultiUse LAB and the LYO-SCALE pilot freeze dryer provide the optimal environment for this purpose. Their core functions are precisely aligned with those of the commercial production facilities. But what exactly do these functions entail?
A wide range of options have been integrated into the pilot system to ensure ideal coordination of filling and closing processes, even for highly complex pharmaceuticals. Among them is a combination filling module that utilizes both peristaltic and rotary piston pumps. This enables ten23 health to address specific requirements, such as very-gentle filling or 100% air-bubble-free closing, in both non-GMP development batches and commercial GMP fill-finish operations.
Even in the pilot plant, product saving functions prevent unnecessary rejects.
Low-particle, maximum GMP-like conditions in the development area at ten23 health. courtesy of ten23 health AG/Alex Hagmann
The vials feature data matrix codes printed on their aluminum caps, which are verified by cameras integrated within the production line.
All MultiUse and vial systems at ten23 health are equipped with product-saving features. One key function is Re-Dosing on Request (ROR): If a container is underfilled, the system automatically adds product until the target weight is reached. This weighing-dosing principle is also applied during system start-up and batch completion to prevent unnecessary product loss through rejected containers. At the beginning of a run, when the system is verifying performance, and at the end of a batch, when product quantities are limited, ROR ensures that containers are not discarded due to underfilling.
As part of 100% in-process control (IPC), in addition to the filling process, the stopper insertion and crimp cap application are also checked inline at high speed and repeated individually if necessary. For this purpose, the system briefly leaves its regular processing mode and switches to individual processing at the corresponding position. These functions are identical on all systems.
While identical functions are essential, true parameter transferability from development to production requires even more. “Our laboratory system uses the same components including sensors, pump types, and software, as our full-scale production systems,” explains Rainer Göller, Team Leader Project Engineering at Optima. “This guarantees identical actuator control and results in physically identical movements.” Jochen Brotz, Director of Sales US at Optima adds, “This design approach allows parameters to be transferred with high precision from the laboratory to production, effectively from identical station to identical station.”
The same requirements for parameter transferability also apply to freeze dryers, with an additional key principle “geometric proportionality.” This means that the physical dimensions influencing the process in both development-scale and GMP production freeze dryers are proportionally identical. This concept is reflected in specific design elements, such as matching shelf thicknesses, proportionally scaled valve sizes between drying chambers and condensers, and consistent ratios between shelf surface areas and the cold surface areas of the condensers. When these and other critical dimensions are maintained in proportion, it allows for example the accurate scaling of heat transfer coefficients, from steel components to glass containers, as well as the reliable transfer of steam volume flow characteristics.
As a result, pilot and production systems are nearly identical in their geometric and physical configurations. Optima’s entire freeze dryer portfolio is built on this principle, ensuring scalable, predictable, and reproducible performance from development through to commercial manufacturing. In addition, ten23 health ensures that the manufacturing processes at both the pilot system and all GMP equipment are equipped with representative and comparable materials. This includes the use of single-use compounding and holding vessels, filtration systems, and filling manifolds. These components are selected to enable thorough evaluation of material compatibility, extractables, leachables, and other critical quality attributes.
Format changes are primarily facilitated by a servo-motor-driven adjustable gripper rake, allowing flexible handling of various container types and wide format ranges on the main conveyor. Additionally, Optima has developed plug-in format components that can accommodate multiple syringe formats per format part, allowing for rapid and efficient changeovers.
The system incorporates several functions and features that fully comply with Annex 1 requirements. Notably, this project introduces the first mechanical material transport system that connects directly to a Restricted Transfer Port (RTP) in the system. A rail-guided cart picks up machine setup components and consumables and transports them internally via glove access points.
This innovative approach largely eliminates manual transfer of materials from glove to glove, significantly reducing glove usage and minimizing critical glove contacts with product-exposed materials – both key considerations under Annex 1. Additionally, the system improves ergonomics by facilitating the movement of heavier parts with ease.This MultiUse system delivers high throughput, achieving an output of up to 13,000 containers per hour.
A closer look at the 8-laned MultiUse system, which will be implemented in the next project phase at the ten23 health Visp site, reveals several unique features. One such innovation is the reuse of plastic tubs and trays that initially hold primary packaging components. After the fill-finish process, the filled and closed containers are returned to these same tubs and trays.
To assist this, the tubs and trays are removed from the isolator after de-nesting and transported to the end of the MultiUse line, rather than being discarded. This approach eliminates the need for time-consuming and resource-intensive autoclaving and decontamination of stainless-steel trays. The result is a significant reduction in chemical usage, energy consumption, and operational effort, aligning seamlessly with ten23 health’s commitment to sustainability and resource efficiency.
Another distinctive aspect of the MultiUse system is its gentle handling of containers, which eliminates any glass-to-glass contact, including during the critical vial crimping process. Moreover, the system intelligently compensates for potential empty spaces in trays. At the end of the line, an oval conveyor equipped with “movers” selectively presents only those positions occupied by containers for robotic pick-up. The robot then carefully places these inspected containers into plastic trays, effectively managing any gaps caused by rejected units and ensuring optimal tray utilization.
In addition to the 100% in-process control (IPC) functions previously described, the system incorporates further advanced monitoring capabilities. Cameras verify the precise positioning of stoppers in cartridges, pre-filled syringes, and vials during production. They also ensure that crimping remains within specified tolerances.
Moreover, high-speed cameras continuously capture critical processes throughout the system. These recordings are stored temporarily in a ring buffer, unless a system fault occurs, in which case the relevant footage, along with a defined time period before and after the event, is permanently archived.
This setup offers significant advantages: Any operator interventions can be verified for GMP compliance, and if container removals become necessary, the recordings allow for precise identification and documentation of the affected units.
The development facilities are engineered to be representative down to the smallest detail – for instance, matching the heat transfer coefficients of the installation surfaces. This precision ensures that process parameters are fully scalable.
The central robot transports vials throughout the development process on “Line 0”, including loading the laboratory freeze dryer’s loading system.
A brief overview of the extensive vial line (“Line 3”) with and isolator and two freeze dryers, that was ready for iFAT in June 2025. This system, too, is an integrated system with isolators. The process begins with the vials passing through a washing machine and sterilization tunnel, followed by filling and closing via a four-position combined dosing system that integrates peristaltic and rotary piston pumps.
After insertion of standard and lyophilized stoppers, two Optima freeze dryers are loaded through dedicated systems and controlled independently. The line features comprehensive 100% in-process control to ensure product quality. This modular line offers flexible operation, allowing independent freeze-drying or continuous filling and closing processes. A crimping machine completes the line. Each freeze dryer occupies a footprint of 12.5 m², and the filling and closing line is designed to accommodate container sizes ranging from 2R to 20R.
All three new systems were customized to integrate seamlessly with the existing facilities and to meet ten23 health’s specific customer requirements. For instance, the pilot freeze dryer was engineered to be modular, allowing it to be disassembled for transport and moved to the third floor via the building’s existing freight elevator.
A key advantage of our pilot plant is the efficiency gains for our customers.
