INTRODUCTION

Cell and gene therapies (CGTs) represent one of the most transformative advances in modern medicine. These living drugs offer the potential for one-time cures for conditions previously considered incurable. But traditional biologics manufacturing sys­tems were never designed to handle the complexity, variability, and patient-specific nature of CGTs, meaning an entire new par­adigm was needed.

Unlike conventional pharmaceuticals, autologous CGTs – particularly approved cell therapies, which are primarily chimeric antigen receptor (CAR) T-cell therapies – require personalized processing, where a patient’s own cells are collected, modified and returned, all under strict timelines and sterile conditions. This creates immense pressure on manufacturing facilities, which still rely heavily on manual labor, open systems, and fragmented workflows.

Now, amid shifting Food and Drug Administration (FDA) pri­orities as well as developing geopolitical considerations, US com­panies are entering a new regulatory era, one that will define how CGTs are scaled, distributed, and delivered domestically. De­spite the uncertainty of this moment, three major trends are un­changed and continue to shape this new era: a mandate for domestic manufacturing, an emphasis on novel platform tech­nologies, and a push toward automation and standardization to meet total patient demand.

WHY THE US IS REASSERTING MANUFACTURING CONTROL

Lawmakers have shown increasing urgency to source life sci­ences manufacturing within the US. This largely reflects both do­mestic political realities and security concerns. In June, the FDA invoked a Biden-era data-security rule to pause new clinical trials that ship American patients’ living cells to China and certain other countries for processing. The rules were designed to safeguard American health and genomic data from being accessed or processed in “high-risk” countries.¹ In parallel, the Department of Defense and an allied bipartisan coalition in Congress contin­ues to advance the BIOSECURE Act, which would bar federal agencies from funding therapies, or even contracting for dispos­able gloves, if any tier of the supply chain relies on biotech “com­panies of concern” headquartered overseas.

Both the BIOSECURE Act and the data security rules reflect a coordinated policy shift aiming to restrict the offshoring of clini­cal-grade materials and genomic data to certain nations, includ­ing China. They are also accelerating the push for domestic CGT manufacturing.

The practical implications become vivid when we revisit the early days of CAR T development. Before US manufacturing net­works were established for certain cell therapies, such as Carvykti (ciltacabtagene autoleucel), there were cases of US patients trav­eling to China when they ran out of options.² Back then, the in­convenience was framed as an unavoidable cost of innovation. Today, the same design would be unacceptable – in fact, even the transport of patient-derived materials would be a no-go for trial participants, payers, investigators, and regulators worried that genomic data collected from immune cells could be siphoned off into foreign databases.

REEVALUATING CAPACITY IN A SHIFTING LANDSCAPE

If a CAR T manufacturing process be­gins in America, having it end in America simplifies the issue. Resolving it means addressing the disconnect between thera­peutic innovation in CGT and the infra­structure required to deliver it at scale. There have been multiple efforts around the world to address this friction between cutting-edge science and capacity-limited manufacturing systems. Between 2018 and 2022, every major pharmaceutical company in the space, as well as multiple CDMOs and a herd of venture-backed start-ups, announced brand-new CGT fa­cilities.

Some of that momentum has re­versed. A few examples: over the past 2 years, AGC Biologics mothballed its CGT plant in Colorado, citing under-utilization; Rentschler Biopharma decided to retool its Stevenage asset for conventional biolog­ics; and AmplifyBio filed for bankruptcy after macro-volatility throttled early-phase demand.^3,4 These announcements might appear as evidence that we’ve over-built – and yet, CAR T demand today is both drastically unmet and poised for rapid ex­pansion.

A closer look reveals a mismatch be­tween square footage and utility. For one, much of the capacity was constructed overseas, of decreasing value in the cur­rent climate. Even in the US, CGT manu­facturers built capacity with largely legacy technologies for yesterday’s way of work­ing, then realized too late that the goal­posts had moved. Many of those new suites were engineered around open, manual workflows that top out at a few hundred batches per year. They may sit thousands of miles from the patients they intend to serve and depend on long lead-time technology transfers that make next-generation upgrades painfully slow.

The incrementalism these facilities re­lied on is insufficient because their existing systems have proven unscalable. Mean­while, the appeal of CAR T-cell technology is growing. Autologous CAR T therapy was once reserved for adults whose blood can­cers had resisted every other modality. Less than ten years later the evidence is build­ing toward frontline use, and coming ap­provals for therapies in larger indications like autoimmune disease are expected to dwarf the addressable market for current approved drugs.⁵ Layer on other cell-based therapies like ex vivo gene-edited therapies and novel cell therapy technolo­gies on the horizon, and the mismatch grows wider. Older multiproduct suites cannot efficiently flex to sufficient volume.

REGULATORY ALIGNMENT

This is one aspect of what FDA’s evolving regulatory stance now seeks to address. FDA has introduced a number of programs to lower the barriers to innova­tion, reduce time to market, and increase patient access to CGTs. Programs like Sup­port for clinical Trials Advancing Rare dis­ease Therapeutics (START) offer early and frequent engagement with FDA reviewers, reducing uncertainty, avoiding costly pro­tocol revisions, and accelerating trial readiness.⁶ Another is Regenerative Medi­cine Advanced Therapy (RMAT) designa­tion, which reduces the time between clinical milestones and commercial ap­proval, critical for companies investing heavily in infrastructure for one or more high-risk CGT assets.⁷

The agency also recognizes that to meet growing demand, CGT manufactur­ers need to adopt novel technologies that are scalable, efficient, and regulatory-ready. In 2024, FDA finalized its Advanced Manufacturing Technologies (AMT) desig­nation program aimed at reducing manu­facturing bottlenecks by encouraging early adoption of platforms that can improve product consistency, reduce costs, and in­crease scalability. The AMT program’s first disclosed designation was in cell therapy, for Cellares’ Cell Shuttle, a fully closed, automated, end-to-end manufacturing platform purpose-built for the modality.⁸ Under the AMT designation, companies utilizing the Cell Shuttle access expedited FDA review, shorter IND/BLA timelines, and a streamlined regulatory path for ad­ditional therapies built on the same tech­nology. The shortened regulatory timeline is especially attractive in competitive spaces such as BCMA and GPC3. As such, we expect other CGT manufacturing tech­nology companies in the space to similarly pursue their own AMT designations.

ADVANCED TECH MEETING US MANUFACTURING NEED

The US has an opportunity to lead by embracing an increasingly automated, standardized CGT manufacturing model designed for the realities of 2025 and be­yond.

FDA support for AMT is far from the only reason to embrace next-generation manufacturing for CGTs. Domestic cell therapy developers are also attracted to advanced manufacturing technology ben­efits like the ability to lower costs, a major existing limitation to cell therapy accessi­bility. A number of elements related to novel manufacturing approaches can re­duce batch manufacturing costs, including streamlining facility designs to support multi-product manufacturing based on the capabilities of these novel platform tech­nologies. These novel and fully closed technologies like the Cellares Cell Shuttle can also be deployed in controlled non-classified environments instead of the more stringent ISO 7 suites that have dominated legacy autologous manufactur­ing sites, which can significantly lower fa­cility buildout costs.

Unlike traditional approaches, stan­dardization through next-generation man­ufacturing has the potential for quick implementation and rapid scale-up accel­eration. By integrating with software-dri­ven automation, transferring and replicating manufacturing onto additional devices – in any location – is much more straightforward than traditional require­ments.

While accelerated manufacturing platforms have streamlined upstream processes, downstream bottlenecks, par­ticularly in quality control (QC), remain a hurdle. As the volume and complexity of CGT products increase, the demand on QC infrastructure ramps up, often leading to release delays and added variability.

To meet this challenge, interest is growing in fully automated QC systems that can integrate directly into the produc­tion workflow. Like manufacturing systems, these platforms aim to reduce manual in­terventions, enable real-time data capture and support continuous release models, all while maintaining compliance with evolving FDA standards.

Cellares’ automated QC platform is called the Cell Q. These stations bring rapid sterility, identity, and viability meas­urements in line. This creates a real-time feedback loop that immediately improves process control. That transformation is ex­actly what FDA’s Center for Biologics Eval­uation and Research (CBER) envisioned when it asked industry to align around quality-by-design principles rather than rely on end-product testing alone.

This evolution aligns with the princi­ples of Industry 4.0, where manufacturing systems are digitally connected, self-mon­itoring, and adaptive. In the context of CGT, it means creating fully integrated, in­telligent facilities that can scale flexibly, re­spond to demand signals and ensure consistent quality, without duplicating in­frastructure across geographies. The emergence of the integrated development and manufacturing organization model, which brings together process develop­ment, manufacturing, automation, and quality within a unified, software-inte­grated platform, is helping to make this vi­sion a reality. Rather than building more brick-and-mortar capacity, CGT compa­nies can now access the benefits of mod­ular, cross-functional units that deliver global scalability through digital replica­tion.

By embedding quality into every layer of production, these next-gen systems offer more than operational speed; they enable resilience, precision, and readiness for the next phase of CGT expansion.

BUILDING A CROSS-FUNCTIONAL CGT MANUFACTURING ECOSPHERE

Despite today’s uncertainty, advanced American manufacturing capabilities in CGT may see additional opportunity given tilt from ongoing tariff risks. Trade relation­ships that once looked predictable, when many manufacturing plants outside of the US were greenlit, now sit on shakier ground. If US lawmakers impose retalia­tory duties on biologics, overseas produc­tion costs could spike overnight. Domestic capability would ultimately be faster and less expensive.

The industry is facing a decision point. The existing trajectory is widely acknowl­edged as unsustainable, putting at risk the future of the CGT industry and the fate of patients awaiting potential cures. To bridge the gap between innovation and infra­structure, CGT companies must take proactive steps now. This includes leverag­ing platform technologies that align with FDA incentives and enable scalable, re­peatable manufacturing. Standardization through automation can strengthen both upstream and downstream workflows to ensure end-to-end readiness for clinical and commercial demands.

With strategic investment and thoughtful adoption of next-generation manufacturing systems, US-based CGT developers are uniquely positioned to lead the next wave of innovation, reducing cost, accelerating time to market, and staying ahead of evolving regulatory expectations.

None of this is an abstract policy de­bate. The children with relapsed neurob­lastoma, the adults battling refractory multiple myeloma, and the families con­fronting rare genetic disorders care only that a curative therapy is available when they need it. Meeting that expectation is more than a commercial opportunity; it is a moral obligation.

In 2024, I lost my father to erythrob­lastic acute myeloid leukemia. While there were limited treatment options available for him, science has given us the tools to re-engineer living cells into medicines and transform patient treatment. Continued in­novation and investment within the space to find potential cures in the future will largely depend on our ability to transform the manufacturing paradigm and ensure these therapeutics can reach every eligible patient in a timely, affordable, and secure manner and help patients similar to my fa­ther. In the process, there are worthwhile opportunities to strengthen domestic manufacturing and ensure another generation of American biopharma leadership. But success in CGT manufacturing will belong to those who scale smartly, adapt fast, and stay aligned with a shifting regulatory landscape.

REFERENCES

1. FDA Halts New Clinical Trials That Export Americans’ Cells to Foreign Labs in Hostile Countries for Genetic Engineer­ing [Internet]. U.S. Food and Drug Administration. 2025. Available from: https://www.fda.gov/news-events/press-announcements/fda-halts-new-clinical-trials-export-ameri­cans-cells-foreign-labs-hostile-countries-genetic.
2. Ciltacabtagene Autoleucel and CARTITUDE Findings in Re­lapsed/Refractory Myeloma | Blood Cancers Today [Inter­net]. Blood Cancers Today. 2025 [cited 2025 Jul 21]. Available from: https://www.bloodcancerstoday.com/post/ciltacabtagene-autoleucel-and-cartitude-findings-in-relapsed-refractory-myeloma.
3. Ojha S. CDMO AGC places CO plant on ice amid turbu­lent CGT economy [Internet]. Bioprocessintl.com. 2024 [cited 2025 Jul 21]. Available from: https://www.biopro­cessintl.com/facilities-capacity/cdmo-agc-places-co-plant-on-ice-amid-turbulent-cgt-economy.
4. Rentschler Biopharma announces strategic realignment of its global business operations [Internet]. GlobeNewswire News Room. Rentschler Biopharma SE; 2025 [cited 2025 Jul 21]. Available from: https://www.globenewswire.com/news-release/2025/01/30/3017990/0/en/Rentschler-Bio­pharma-announces-strategic-realignment-of-its-global-business-operations.html.
5. Neelapu SS, Dickinson M, Munoz J, Ulrickson ML, Thieble­mont C, Oluwole OO, et al. Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial. Nature Medicine. 2022 Mar 21;28(4):735–42.
6. 28th Annual Meeting Recap: CMC Symposium + Work­shop, RAC Symposium, Global Fireside Chat | ASGCT – American Society of Gene & Cell Therapy [Internet]. Asgct.org. 2025 [cited 2025 Jul 21]. Available from: https://www.asgct.org/publications/news/june-2025/2025-annual-meeting-cmc-rac-global-fireside-chat.
7. Center for Biologics Evaluation and Research. Regenera­tive Medicine Advanced Therapy Designation [Internet]. U.S. Food and Drug Administration. 2019. Available from: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/regenerative-medicine-advanced-therapy-designation.
8. Cellares’ Cell Shuttle Receives FDA Advanced Manufactur­ing Technology (AMT) Designation for Automated Cell Therapy Manufacturing [Internet]. Cellares. 2025 [cited 2025 Jul 21]. Available from: https://www.cellares.com/news/cellares-cell-shuttle-re­ceives-fda-advanced-manufacturing-technology-amt-des­ignation-for-automated-cell-therapy-manufacturing/.

John Tomtishen is a former Senior Vice President & General Manager, IDMO Business, at Cellares. He is a proven, results driven Business Operations and CMC strategic leader with broad experience in organizational and operational planning, technical development, and business transformation. He has extensive career experience within cell and gene therapies (Kymriah – tisagenlecleucel and Carvykti – ciltacabtagene autoleucel), biologics (Herceptin – trastuzumab), and vaccines (M-M-R II and ProQuad). A recognized expert and leader within the Biopharmaceutical and Cell and Gene Therapy Industry serving as the CMC Committee Chair with the American Society of Gene and Cell Therapy (ASGCT), the Manufacturing Advisory Committee Co-Chair with BioNJ, a member of the Cell Therapy Advisory Committee with the Alliance for Regenerative Medicine (ARM), and a member of the Advisory Board for the New Jersey Aseptic Process and Biomanufacturing Coalition. The views expressed in this op-ed are solely those of the author and do not necessarily reflect the views or positions of Cellares.