How to successfully scale-up clinical cell therapy production

A great beginning in an emerging field

CO.DON AG is a biopharmaceutical company that develops, produces, and distributes autologous cell therapies for the treatment of articular cartilage defects.  CO.DON was established in 1993 and is based in Germany.

CO.DON’s Spherox is the only available Advanced Therapy Medicinal Product (ATMP) for cartilage repair with EMA approval. It was developed under isolation technology since the beginning of the nineties.

Then the situation changed…

After receiving EMA product approval in 2017, the isolator with integrated incubation approach began to show its limits, given the foreseen increase in production requirements. Fully loaded, integrated incubators meant the isolator was at a dead end. In case of any technical issues with the isolators or incubators, the cells could not be transferred to another system.

These limits brought CO.DON to dream of a new site to handle production expansion while improving flexibility, traceability, and commercial sustainability.

The new challenge

“How do we increase and maximize cell production capacity while keeping or improving the quality standards, allow for best product management and contain the production costs for an optimal cost-efficiency ratio?”

What did CO.DON desire and Comecer deliver?

A new manufacturing facility serving 4500 patient batches per year, with the ability to offer:

• 18.000+ days of quarantine for the biopsies coming from the surgical suite (4500 patient samples x 4 days of quarantine each)
• 72.000+ IN/OUT operations for cell checks and media changes (each patient’s cells require a total of 16 handing steps)
• 229.000+ days of total incubation time!

As additional constraints, the space available was limited (a total of 300 sqm for the laboratory area) and the request to keep the lowest possible environmental classification was a must.

Addressing the requirements: from customer needs review to validation to deployment

CO.DON approached Comecer, as at that time they had just announced their new MCCI and Flexycult^TM systems.

Comecer then developed with CO.DON a customized, turnkey solution addressing the requested requirements (URS) using these two systems.

Modular Cell Culture Isolator: a Comecer isolator integrated with all the necessary equipment to perform Cell Therapy processing (incubator, centrifuge, refrigerator, freezer, microscope, and more).

Flexycult: a flexible, docking incubation system running under grade A, with a sterile interface to the isolator and docked into a separate, upgradable ground base where all the utilities are managed.

The new CO.DON plant is currently equipped with:

• 3 isolator units in a Grade D environment for processing under Grade A.
• 144 patient-specific Flexycult incubators in 16 docking stations – all contained within a CNC environment.
• A fully robotic incubator retrieval system

The automatic incubator module transportation (from docking station to isolator) is controlled by a robotic system and dedicated software (Flexycult Management System – FMS).

Automatic incubator module transportation system that moves an incubator from the docking station to the isolator

The system is completed by interactive communication among modules, isolators, and operators, automatic tracking, and full SOP assistance for the operators.

 Customer satisfaction achieved!

Only 11 months after the contract was signed, on schedule and within budget, Comecer delivered all the equipment, assembled it in the new facility and then carried out an intensive validation and qualification process.
The new CO.DON facility is operational and fully authorized under a German BLA for internal and contract manufacturing cell production, since January 2020.

What the customer said

“When you can touch the equipment and see how it was built – from the design through to assembly and installation on site – it really gives you a thrill.”

Dr Andreas Eberle, Vice President Technical Operations, CO.DON AG, about the installation of the plant

The CO.DON project and other cell and gene therapy references are detailed in Comecer’s ATMP/C&GT Catalogue. We invite you to take a look.

About Comecer

Our ATMP/C&GT catalogue presents our products, technologies and contains an updated reference list with cases and challenges descriptions.
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