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Manufacturing for a field that refuses to stand still

A non linear field An expanding landscape of CGT therapy modalitiesVariability also comes from patient biologyImplications for manufacturing approaches in CGTDesigning with flexibility and adaptability in mindCollaborative innovation as a requirementThe regulatory angleScinus' drive for impact

Ruud Das, PhD, CSO 7 July 2026


Cell and gene therapy manufacturing is often approached as if the field evolves from one dominant modality to the next.

In reality, its development has been anything but linear.

A non linear field 


8,144. That’s the amount of times the ISCT’s 2006 position statement paper on minimal mesenchymal stromal cells (MSCs) criteria has been cited at this time of writing (April 2026). This paper was written at a time when interest in the therapeutic potential of MSCs was in full swing. The multiple potential modes of action made these cells a particularly interesting source for various cell therapy applications.
But by 2014, things looked a bit different. Clinical success of MSC-based therapies, for example in cardiovascular disease (especially myocardial infarction) or autoimmune/inflammatory diseases, was inconsistent. At the same time, the new kid on the block was about to arrive with major potential for blood malignancies.
That new kid on the block (CAR-T for those that were wondering), demonstrated clear and meaningful clinical outcomes. It was the success story that the cell therapy field needed. But, from a manufacturing point of view, it was quite the pivot. No longer looking at expansion of adherent cells (MSCs), but cultivation of suspension cells with multiple unit operations (selection, activation, CAR introduction) became the dominant application. But did we really want to discount the “old guard” already?

An expanding landscape of CGT therapy modalities


Fast forward to today and it looks like MSCs are something of a comeback story. December 2024 already saw the FDA approval of Ryoncil, an MSC-based therapy, for steroid-refractory acute graft-versus-host disease. In addition, years of research into the workings of MSCs has opened new possibilities. MSC-derived extracellular vesicle (EV) therapies are now in clinical development, bringing with them new manufacturing challenges.

Rather than converging, the field is getting broader and broader, with ever more cell types competing for their spot in the limelight. Examples include, iPSCs, natural killer cells, tumor-infiltrating lymphocytes, dendritic cells, organoids, they all have the potential to address one or more clinical or biological problems. This further reinforces the diversification of the field.

Variability also comes from patient biology


You would think such a diversity of modalities is sufficient complexity to deal with, and you would be right. You would also be disappointed. Variability within one treatment modality can be similarly high. Kadri et al. (Cell Mol Immunol, 2023) highlighted the potential biological variations between patients receiving MSC treatment for GvHD that led to responders and non-responders.

Similarly, the patient-specific immune biology of those receiving CAR-T treatment can determine success or failure. The field is working hard to understand both sides of the coin; product specifications and patient biology. But they do impact the way we should think about manufacturing as we continue to get better understanding of the treatment modalities we develop.

Implications for manufacturing approaches in CGT


While there’s no denying the impact of CAR-T therapies, that success story is also in flux. Insights into the impact of T cell subset composition are already changing our understanding of what the CAR-T product should be, and the advent of in-vivo CAR-T solutions certainly also throws a wrench into manufacturing paradigms. Therefore, it serves the field to think of flexible solutions. Ones that can better handle shifting demands and that can more readily incorporate technological advances. The lock-in due to over-optimization for a single modality slows adoptions of advances in manufacturing. Allowing for this adaptability is, therefore, good practice in future-proofing cell and gene therapy manufacturing technologies.

Designing with flexibility and adaptability in mind


 The capability of technologies to integrate plays an important role in this concept. Physical integration is important, but integration of software capabilities is increasingly important. This is especially true for those technologies that are integrated to provide enhanced feedback on culture performance. 

First determining critical process parameters (CPPs) in process development, and subsequently control of CPPs in production can require integration of multiple sensing and control technologies. Addition of such enhanced sensing capabilities will allow us to further fine-tune cell and gene therapy manufacturing as we gather more data on process and patient variability. However, determining these CPPs is a slow process and over-investing in sensing early on can make the process unnecessarily complex and costly. Flexibility remains crucial.

Collaborative innovation as a requirement


Collaborative innovation is what brings our field further in significant ways. Technology innovations from start-up to handle different unit operations, advanced sensor concepts developed in universities of technology, real-world validation in academic hospitals, they all play their role. That’s why long-term partnerships and real ecosystem thinking are needed if we want to make these developments and their resultant therapies sustainable.

The regulatory angle


From a regulatory perspective, the increasing emphasis on flexibility does not necessarily change the pathway within a given manufacturing approach. Once a process is defined and validated, the expectations around consistency, comparability, and control remain largely unchanged. The greater challenge lies elsewhere. As the field evolves, new technologies are continuously introduced, whether in upstream processing, sensing, or control strategies, each new implementation requires assessment.

Encouragingly, initial steps are being taken to address this. The FDA’s Advanced Manufacturing Technology (AMT) designation is one example of how regulators are starting to engage more proactively with novel manufacturing approaches. Such initiatives acknowledge that innovation in CGT manufacturing can be as critical as advances in biology. At the same time, they highlight the need for clear frameworks to evaluate new technologies in a consistent and efficient way. As CGT continues to evolve, the ability to integrate innovation without creating unnecessary regulatory burden will be an important factor in translating technological progress into clinical impact.

Scinus' drive for impact


The future of CGT manufacturing will most certainly bring in many new innovations and we need the ability, both from a technology and organizational perspective, to navigate the diversity and changes. There is a lot to be excited about in the realm of cell therapy. This year’s ISCT annual meeting even heralds the “Golden age of cell & gene therapy”. It will be interesting to see where the next major successes come from, but one thing is certain: cell and gene therapy modalities will remain diverse and dynamic, and as a result, so will CGT manufacturing. So we need technology that is flexible enough to follow evolutions in the field and collaborative innovation to bring it all together.


Key Opinion Leader

As CGT continues to evolve, the ability to integrate innovation without creating unnecessary regulatory burden will be an important factor in translating technological progress into clinical impact.

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