Successfully closing the manufacturing process is the key in scaling of a therapy. For the Arcelis therapy, this was achieved through the development of closed consumables. Seven separate process stations, each with a dedicated consumable with sterile assemblies of OEM and custom plastic components were designed and implemented.

The consumables were designed to maintain cell viability while performing many functions, including:

• Structural temperature control
• Fluid control
• Internal humidity
• Vapor management
• Centrifugal and magnetic separation
• Electric field management

Successfully closing end-to-end manufacturing allowed production in lower-class cleanrooms, and multiple patient processes to be run in parallel in the same facility resulting in a substantial decrease in the cost of therapy.

During this project, Invetech developed methods to undertake all major cell therapy processing steps within closed disposables, as well as some process steps specific to Argos. An example of this being RNA extraction from tumor homogenate and amplification. Through our collaboration, Argos was pioneering in taking consumables with closed processing to the FDA.

In discussions with the agency, there was support for

furthering the development of this equipment and associated consumables to enable processing of multiple patient samples in closed disposables in the same manufacturing area. The innovative step of utilizing assets to enable high-value processing on expensive equipment and low-value processing in simple incubators is now a recognized industry strategy. 

Invetech’s consultative approach is what sets us apart from equipment manufacturers and Contract Manufacturing Organizations (CMOs). We collaborated closely with Argos to ensure development decisions were considered from both a business and technical perspective. Our teams had regular steering committee meetings and weekly teleconferences.

Argos personnel also visited our offices to test and

assess prototypes, after which prototype systems were shipped to Argos for ongoing in-house process development. Furthermore, we installed one of our own engineers in the Argos team for nine months. External to our development activities, we also advised Argos on selection of an external disposables partner, providing a shortlist and recommendation based on our research.

We managed risk using a number of tools and methodologies throughout the development, including the consistent use of risk watch lists, failure modes and effects analysis (FMEA) and sophisticated project tracking and analysis tools. FMEA enabled understanding and characterization of risks early which were then addressed through multiple agile prototype and test rounds, seeking external advice, establishing partnerships, or working with Argos and others to explore best approaches. We were also able to implement the use of common modules in this project, by identifying core elements of functionality, such as mechanical hardware, control systems and consumables, that were utilized across several of the seven platforms.

Invetech’s services encompass human factors engineering, user interface design, and user experience design. These services at a basic level deliver appropriate ergonomics and ensure designs that reduce or remove opportunities for operator error.

In developing a complete manufacturing system, our challenges extended to the larger environment beyond individual machine automation including minimizing equipment set-up and tear-down times, developing intuitive and simple-to-use touch-screen interfaces, and designing dedicated support equipment such as trolleys for handling the heavy components.

Full-scale prototypes of each system were developed with every interaction tested, assessed and optimized through the entire manufacturing chain.

The platforms were designed to connect to a manufacturing execution system (MES), which allows for system connectivity and control through the entire facility. The platforms were also designed for secure remote monitoring and control, including software update capability. This allows a single control center to manage the configuration of every platform globally and for functionality like remote fault assessment.