Guest Column | June 18, 2025

Exploring The Market For Closed-Loop Cell Therapy Production

By Shubhranshu Gupta, Ph.D., cell therapy expert

Drip Irrigation Equipment, hospital operations-GettyImages-882905988

The adoption of closed-loop automation in cell therapy manufacturing has accelerated significantly since 2023, driven by the need to address scalability, contamination risks, and regulatory compliance.

In part 1 of this discussion, I explored the significant capacity issues created by all-manual processes. Here, I’ll describe the market landscape for automated closed-loop systems and some of the major hurdles the industry must clear to roll them out.

Major contract development and manufacturing organizations (CDMOs) now collectively serve approximately 65% of the global cell therapy market,¹ with closed-loop systems accounting for 54.3% of their installed capacity.² Below is the implementation landscape across some of the key players and their combined impact.

This is part 2 of a discussion about closed-loop manufacturing platforms. Click here to read more about how closed loop systems solve many of the problems inherent with traditional open systems.

Lonza: Cocoon Platform

Lonza leads the industry with its Cocoon Platform, a fully closed automated system deployed in over 150 instruments globally.^3,4 Considering that each Cocoon unit can process one patient batch at a time that takes up to 10 days,^4,5 this adds up to a total capacity of roughly 36 batches/year for one unit and 5,000+ batches annually across all 150 installed units. This platform supports decentralized manufacturing, reducing vein-to-vein times (V2VT) to ~10 days from a median 38.3 days⁶ (as with the centralized and labor-intensive manufacturing processes), which amounts to a reduction of over 70% V2VT. This can result in a significant increase in patient accessibility and life expectancy since more patients can get a CAR-T dose within just a couple of weeks of leukapheresis. For instance, a reduction of just 55% V2VT increases life expectancy of relapsed/refractory large B-cell lymphoma (R/R LBCL) patients by more than three years.⁷ Lonza’s partnership with Vertex for CASGEVY (exa-cel) production highlights its role in commercial-scale gene therapies, holding 18%-22% of market share in automated end-to-end closed system manufacturing.⁸

Cellares: Cell Shuttle

Cellares’ Cell Shuttle received FDA Advanced Manufacturing Technology (AMT) designation in 2025, enabling priority review for therapies manufactured on its platform.⁹ Each Cell Shuttle is capable of producing 16 batches in parallel versus one batch at a time, achieving 1,000+ annual batches/shuttle for a standard CAR-T manufacturing protocol. With just one “smart factory” capable of accommodating 38 cell shuttles, this projects to a whopping 40,000 batches/year, and 380,000 batches/year across all three smart factories (New Jersey, EU, Japan). Currently, Cellares’ market share in automated end-to-end closed system manufacturing is estimated to be 10%-14%.⁸ However, considering its development of more smart factories with time, its market share will likely increase in the years to come.

Thermo Fisher Scientific: Gibco CTS Rotea Counterflow Centrifugation System

Thermo Fisher Scientific’s CTS Rotea Counterflow Centrifugation System exemplifies closed-loop automation in leukopak processing used in both autologous and PBMC-derived allogeneic cell therapy manufacturing. The CTS Rotea Counterflow Centrifugation System processes leukopaks at a speed of 5.3 L/hour with >90% PBMC recovery and >95% cell viability,¹⁰ thereby reducing the processing time from over 2 hours (using manual Ficoll separation) to <30 minutes. However, it’s to be noted that the Rotea system automates just the leukopak processing step, and it needs to be coupled to additional modular automation components from other platforms for downstream activation, transduction, and expansion steps to enable fully end-to-end automated manufacturing.

Miltenyi Biotec: CliniMACS Platform

Miltenyi’s CliniMACS Prodigy in combination with CliniMACS Electroporator automates CAR-T production from cell selection to formulation, producing 2.5 × 10⁹ CAR T cells/run from a starting number of 2 x 10⁸ non-edited T cells derived from leukopaks within two weeks.¹¹ Its fully end-to-end closed automated system enables simplified technology transfer from R&D to GMP manufacturing facility, with a manufacturing success rate of 89% in Grade C cleanrooms.¹² While the current estimated market share held by Miltenyi stands at 4%-8%, more widespread adoption of its CliniMACS platform could increase its market shares in the next few years as the cell therapy field embraces end-to-end automation in its manufacturing protocol to reduce the burden of cost.

Cytiva: Sefia Platform

Cytiva developed the Sefia cell therapy manufacturing platform in collaboration with Kite Pharma, a global leader in autologous CAR T cell therapies. The platform consists of two main components: the Sefia Select system for cell isolation, harvest, and formulation and the Sefia Expansion system for cell activation, transduction, and expansion. The Sefia platform was designed to help increase manufactured doses by up to 50% per year compared to industry standards.¹³ The platform's modular design allows for the addition of a temperature-controlled thermal mixer that can be used to add DMSO during final formulation step (or to add staining reagents such as antibodies or beads for automating other parts of the cell manufacturing process).¹⁴ This allows scalability from clinical to commercial production from 10 doses/year to 1,000 doses/year within a 297-square-meter facility, while reducing the need for manual operators by 40%.¹⁵ The current estimated market share held by Cytiva hovers around 7%-11%.⁸

Catalent: UpTempo Platform

The UpTempo CAR-T Cell Therapy Platform¹⁶ is a fully closed GMP-compliant platform that can be used for cell therapy manufacturing of both autologous and allogeneic nature, via minimal hands-on operator time. The platform features a fully closed workflow with aseptic automated connections between devices and provides data-driven guidance for process optimization. This modular platform, like many of the above platforms, allows for customization by adding preferred equipment for any purpose. The platform is said to cut the manufacturing time of cell and gene therapy products by half, resulting in 50% faster IND-enabling studies compared to traditional development.

Ori Biotech: IRO Platform

The IRO platform from Ori Biotech represents another significant advancement in cell therapy manufacturing through its closed-system automation, exemplified by its OriConnect System that eliminates manual tube welding and minimizes dead volumes to ensure aseptic processing.¹⁷ The platform’s >50% average transduction rate at an MOI of just 0.5 yields up to 3.5x more transduced cells within a week of expansion.¹⁸ IRO reduces labor by 50%-70% and manufacturing costs by 30%-50%, and it enables manufacturing in less stringent GMP Grade C/D cleanrooms due to its closed design.¹⁷ Its modular scalability from R&D to GMP enables seamless tech transfer, >200x T/NK/CD34+ cell expansion, and ~1,000 annual doses within a 1,000-square-foot facility. However, the platform’s automation is limited to just the activation, transduction, and expansion steps of cell therapy manufacturing,¹⁹ while still relying on manual involvement for selection and final formulation steps, unlike some of the fully end-to-end automated platforms discussed above. Furthermore, its recent commercial launch (2024) necessitates further long-term validation of large-scale reproducibility.

Cellistic: Echo-NK Platform

The Echo-NK manufacturing platform from Cellistic is an advanced closed-system automation for cell therapy production, particularly for iPSC-derived cell manufacturing.²⁰ Its architecture integrates sealed bioreactors, robotic controls, and real-time monitoring to minimize contamination risks and manual intervention, ensuring GMP compliance and process consistency.^21,22,23 This design reduces human error and enhances reproducibility, critical for clinical scalability of feeder-free 3D cultures up to 100 L.

Current Obstacles

Despite the demonstrated benefits of the platforms discussed above, widespread adoption of automated end-to-end systems remains limited due to financial, technical, regulatory, skillset-based, and market-related barriers.

Financial barriers

The high up-front capital expenditure required for automated platforms poses a critical challenge, particularly for small to midsize biotech. For example, implementing automated closed systems often demands more than five times the capital in initial equipment costs vs. manual facilities, alongside facility upgrades for isolator integration.^24,25 While automation reduces long-term labor costs (by an average of 25%), batch failure rates (by an average of 70%), and total COGS (by an average of 130%) while increasing batch numbers (by an average of 100%), the payback period exceeds three to five years (or more) — a timeline misaligned with the funding cycles of venture-backed startups. Additionally, variable reimbursement policies for cell therapies complicate ROI calculations, as payers remain skeptical of automation’s impact on per-dose pricing.²⁶

Technical and operational barriers

Process rigidity in some of the non-modular automated platforms limits adaptability for novel therapies. For instance, CAR-NK workflows requiring unique transduction protocols often clash with the predefined parameters of integrated systems. Furthermore, interoperability gaps between vendors — such as Thermo Fisher’s CTS Rotea and Miltenyi’s CliniMACS — force cell therapy manufacturers into proprietary ecosystems, increasing switching costs and stifling innovation. Legacy facilities face additional challenges retrofitting Grade B/C/D cleanrooms to accommodate robotic arms and closed bioreactors, with renovation costs exceeding $2 million in up-front capital.²⁷ Furthermore, supply chain fragility for critical consumables, including proprietary cartridges and specialized reagents, can create uncertainties if a modular platform uses a proprietary component from another manufacturer (e.g., Ori Biotech’s IRO platform using Fresenius Kabi’s Lovo system would need Lovo’s Cell Processing Disposable kit), potentially making the entire platform vulnerable during times of disruption (such as a global pandemic).

Regulatory uncertainty

While automated systems enhance consistency, regulators like the FDA and EMA require extensive process validation for each therapy platform combination. For example, replacing manufacturing of an iPSC-derived NK or T cell manufacturing protocol with an automated end-to-end closed platform after IND-approval would trigger full comparability studies,²⁸ adding 12 to 18 months to development timelines. The lack of harmonized standards for real-time release testing in closed systems further delays approvals, especially when the cell therapy product enters a new regulatory jurisdiction.²⁹

Risk aversion and skill gaps

Many manufacturers prioritize manual workflows during early clinical stages to retain flexibility, delaying automation until Phase 3 — a strategy that inadvertently entrenches labor-intensive processes.³⁰ Concurrently, shortages of personnel trained on automated closed-loop platforms, especially if the company is adopting automation at a later stage, could exacerbate adoption delays, thereby relying on increased footprint to scale up/out. Workforce development represents another hurdle, as operating sophisticated closed-loop systems requires cross-disciplinary expertise in cell biology, engineering, and data science that many organizations lack. Additionally, reliance on digital analytics introduces cybersecurity and software dependence risks, mandating robust IT support that can further inflate the variable costs associated with automated manufacturing.

Market fragmentation

The proliferation of competing platforms — at least 11 systems as of 2025³¹ — creates decision paralysis among developers. Without clear industry benchmarks and rapid evolution of this sector, companies hesitate to commit to single-vendor solutions like Cell Shuttle or Rotea, fearing obsolescence, especially when the associated up-front capital expenditure is formidable. This is especially true, now more than ever, due to the AI-revolution, where future enhancements could integrate AI for predictive process optimization and improved sensor technology for granular parameter control. This would also mean that the inherent black-box nature of AI-driven control systems could create additional regulatory transparency concerns, potentially slowing approval processes further.

Conclusion

The cell therapy industry cannot achieve its potential to transform medicine without addressing fundamental manufacturing limitations through closed-loop automation. The technology represents our best opportunity to scale production while maintaining quality and reducing costs, ultimately making these lifesaving treatments accessible to millions of patients worldwide. While automated platforms promise transformative efficiency gains, their adoption hinges on resolving systemic financing models, regulatory harmonization, and workforce development. Initiatives like the FDA’s Emerging Technology Program and EU’s SoHO Regulation could address these barriers, but industrywide collaboration remains critical to unlocking automation’s full potential.

The path forward demands strategic investment in modular platforms that allow gradual transition to full automation, coupled with workforce development programs that build the necessary expertise for operating these sophisticated systems. Digital twin integration and advanced process analytical technologies will be crucial enablers, providing the real-time insights needed for effective closed-loop control.³² The stakes are too high to maintain the status quo; patients whose lives depend on these therapies deserve manufacturing systems that can reliably deliver consistent, high-quality products at scale. The revolution in closed-loop cell therapy manufacturing is not just a technological imperative, it is a moral obligation to the patients we serve.

References:

About The Author:

Shubhranshu Gupta, Ph.D., is a scientist and entrepreneur specializing in cellular immunotherapy, with a focus on CAR T and CAR NK cell therapies for hematological and solid tumors. He is the CEO and CSO at a stealth mode biotech startup that he cofounded in 2024 and serves as a scientific advisor for multiple expert insight networks. Dr. Gupta has held research positions at Caribou Biosciences, Fate Therapeutics, and Baylor College of Medicine. His work includes early discovery pipelines, gene editing, and developing cell-based assays, with several publications in peer-reviewed journals. He earned his Ph.D. in the area of immunological memory in cell therapy at Baylor College of Medicine. Contact him on LinkedIn.

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