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In 2022, the Association for Regenerative Medicine (ARM) reported that over 2,000 clinical trials employed cell therapy, cell-based immuno-oncology, gene therapy, or tissue engineering. The cells required for these clinical interventions are often grown in an adherent culture format. Depending on the indication, one single therapeutic dose might require tens to hundreds of millions of cells.1

As these potentially transformative regenerative therapies move from the R&D bench to process development for the initial manufacturing design paradigm, it is essential to address the challenge of scaling up adherent cell cultures. Although scale-up schemes are situation dependent, universal concerns such as labor, time, and incubator floor space are unavoidable and must be resolved. In addition, if one is partnering with a CDMO, facilitating technology transfer is imperative.

Several factors play critical roles in devising successful cell culture strategies and selecting the optimal scale-up technology: the breadth of the product line to ensure flexibility when transitioning between manufacturing stages, the robustness of the supply chain to safeguard delivery of goods as needed, and deep technical expertise to help tailor solutions from process development though commercialization.

Expertise and thoughtful planning help smooth the process. Corning® field application scientists advise process development teams to include downstream groups, such as manufacturing and materials science and technology, in the early discussions to facilitate the future move toward GMP manufacturing for clinical trials and commercialization.

Fortunately, technological innovations have resulted in many inventive options for adherent cell culture applications over a range of scales by using multilayer vessels that, like skyscrapers on a city landscape, pack more surface area into smaller footprints.

From the Benchtop to Process Development

Typically, the first step in scaling up adherent cultures will involve transitioning from a commonplace well plate or T-flask to a larger vessel. Corning’s broad portfolio provides an array of options, including the Corning HYPERFlask®, HYPERStack®, and CellSTACK® vessels that require only modest changes to traditional 2D cell culture techniques.

Corning CellSTACK culture chambers are available with up to 25,440 cm² of growth area. These culture chambers are easily convertible into closed systems, with available aseptic transfer caps and tubing, to facilitate the transition to GMP production. For convenience, CellSTACK culture chambers are also available preassembled with closed system tubing and aseptic connectors.

The Corning HYPERFlask and HYPERStack cell culture vessels offer more compact solutions. These culture vessels have supporting layers of rigid polystyrene with ultrathin polystyrene growth surfaces that allow for gas exchange. The HYPERFlask is like a traditional T-175 flask in overall footprint but has 10 layers of ultrathin polystyrene for 10× the growth area and is adaptable to a manual or automated process.

The out-of-the-box, closed-system Corning HYPERStack vessels are available up to 36 layers. To reduce handling time, facilitate liquid handling, and improve consistency, single-use manifolds can be used to daisy chain these vessels together. Customization of tubing and adapters support any manufacturing scenario.

Scaling Up Successfully

In a Phase I trial, researchers at the Ottawa Hospital Research Institute’s Cell Manufacturing Facility used the Corning HYPERFlask vessel to manufacture on an as-needed basis single doses of freshly cultured allogeneic bone marrow-derived mesenchymal stem cells (MSCs).2 As the therapy progressed to larger clinical trials, the use of the HYPER technology simplified scale-up to multiple HYPERStack vessels.3

“Hospital-based cell manufacturing facilities often have significant space and staffing constraints, making the more standard scale-up process difficult to accomplish. The Corning HYPERStack system provides a much more manageable platform to reach batch production levels appropriate for the typical scale-up required in academic trials with MSCs,” said David Courtman, PhD, Director of Biotherapeutics at the cell manufacturing facility.

Corning provides many product options. Importantly, experienced field application scientists work together with process development scientists to custom-fashion scale-up strategies that ensure a continual supply of cells throughout the entire commercialization phase.



  1. Rotte A, Frigault MJ, Ansari A, et al. Dose–response correlation for CAR-T cells: a systematic review of clinical studies. Journal for ImmunoTherapy of Cancer 2022;10:DOI: 10.1136/jitc-2022-005678
  2. Khan S, Davila L, Salkhordeh M, et al. cGMP-compatible large-scale production of mesenchymal stem cells (MSCs) in xeno- and serum-free media for allogeneic cell therapies. Cytotherapy 2018: Vol 20(5), Page S42, DOI:10.1016/j.jcyt.2018.02.107.
  3. McIntyre LA, Stewart DJ, Mei SH, et al. Cellular immunotherapy for septic shock. A phase I clinical trial. Am J Respir Crit Care Med. 2018;197(3):337-347. DOI: 10.1164/rccm.201705-1006OC. PMID: 28960096.

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Learn more about Corning’s HYPER technology at www.corning.com/hyper

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