CASE STUDIES

Argos Therapeutics: Manufacturing Solutions for Autologous Cell Therapy Production

Complete manufacturing system delivered technology innovation, novel automation solutions, and substantial IP in the cell therapy manufacturing automation domain.

Client: Argos Therapeutics

Product: Manufacturing Automation Solutions for Autologous Cell Therapy Production

Regulatory Requirements

OSHA, IEC/UL 61010-1, FCC – CFR 47 FCC 15 sub. B., Manufacturing Execution System (MES) certified and 21 CFR Part 11 compliant

Expertise Used

Industrial Automation, Design for High-Throughput Manufacturing, Medical-Grade Plastic Disposable Design, Fluidics, Design for Serviceability, Usability/HFE

Planning for commercial scale-out of an autologous cell therapy

A common challenge in the emerging cell and advanced therapies industry is manual production methods that don’t lend themselves to commercial-scale manufacturing as clinical trials progress. Recognizing this risk, clinical-stage company Argos Therapeutics was looking to commercialize an autologous Dendritic cell therapy (Arcelis), an immunotherapeutic approach for treating and preventing cancers and autoimmune diseases. The company approached Invetech during Phase II clinical trials to commence development of scaled-out manufacturing solutions.

In briefing Invetech, two key challenges were identified for focus. The therapy needed to be produced consistently and repeatedly at a lower cost, and their manual benchtop process was required to be closed in a way that was suited to automation and scale-out, yet supported effective biochemistry. Invetech was engaged to develop a complete manufacturing system that would become the backbone of Argos’ entire purpose-built manufacturing facility plans.

The value Invetech delivered was comprehensive, including technology innovation, novel automation solutions, and substantial IP in the cell therapy manufacturing automation domain.

The Arcelis therapy has not yet been introduced to the market, but the technology developed will be adapted by Argos for developing other therapies. The legacy of the systems and thinking as developed by our partnership with Argos, and our approach to overcoming their manufacturing challenges, will have an ongoing impact on the cell therapy manufacturing systems of the future.

“The automation developed for the Arcelis immunotherapy lowers labor and production costs. With reduced risk of process inconsistency and contamination due to the use of robotics in a closed, airtight system, automation of Arcelis addressed the manufacturing challenges of personalized immunotherapies, and could potentially meet the needs of large patient populations in cancer and infectious diseases.”

Jeff Abbey

President and Chief Executive Office, Argos Therapeutics

Consumable development

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.

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Closing the manufacturing process is the first challenge to be solved

Innovating the cell therapy market

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. 

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Collaboration is key on complex projects

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.

Managing risk with relationship and modules

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.

Designing for error reduction

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.

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The role of connectivity & system integration

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.

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