Does the cell and gene therapy development have to take 8 protracted years, or are we unknowingly leaving speed on the table?

As science gradually conquers the fundamentals of biology and employs living materials to target previously untreatable pathologies, the stages behind the development of such treatments also progress forward. Whilst the prospect of manufacturing cell and gene therapies at the scale of generics is highly appealing, it is the biological complexity and long-term effects that make these living therapeutics clinically valuable. This reality promotes the strategies that could speed up the manufacturing processes, but without compromising their integrity.

Beneath each clinical phase sits a manufacturing cycle that repeats and scales as the therapy moves from a small first trial toward broader patient groups. © Green Elephant Biotech.

The entire production chain of any pharmaceutical, whether an antibiotic or an immunotherapy, from bench to commercialization is notoriously complex and time-consuming. The median development time from first-in-human study to marketing authorization has been estimated to 7.3 years, based on an analysis of 608 innovative drugs (1). Now consider the possible implications for the stated timeline if the compound is a living organism that acts as a therapy, which is the case for cell and gene therapies (CGTs).

Administrative hurdles do not end there. A CGT’s source material has a substantial influence over its scalability, production timeline, and availability. When the cell source originates from the patient as in autologous CGTs, such as Chimeric Antigen Receptor (CAR)-T cells, therapy manufacturing becomes highly individualized. While this aspect minimizes the need for immune suppression, which carries clear clinical advantages, the production process can be delayed even with full patient cooperation, due to factors of starting material variability and downstream quality testing (2, 3).

The most time-intensive element of any therapy development remains the multi-phase clinical trial process, spanning optimal dosage determination in Phase 1, efficacy evaluation in Phase 2, and long-term safety monitoring across Phases 3 and 4. That said, clinical timelines have been compressed before: during COVID-19, the FDA issued authorization for a novel vaccine in under a month under emergency provisions, collapsing the interval between funding and approval (4, 5). Streamlined regulatory pathways are well-established for generic drugs and, with adequate scale-up manufacturing infrastructure and standardized protocols, could become at least partially applicable to CGTs over time.

This piece examines some of the major gene therapy steps and cell therapy manufacturing stages following approval, including the role of viral vectors, and considers the factors that could accelerate these processes going forward. The success stories of FDA-approved therapy products like Kymriah and Luxturna may suggest that the bench-to-bedside pipeline is well-mapped. At the same time, despite double the average FDA approval rate at 19% for CGTs to date, prohibitive upfront costs and a complex manufacturing rulebook, compelled by how these therapies are produced, continue to keep them out of reach for many patients who need them (6).

The multi-stage process that extracts cells to shape them into a living precision medicine

Most CGT pipelines follow a common sequence, with context-dependent variations: cell collection from the patient or a donor, transduction, cell expansion, harvesting, cryopreservation, and quality control. The first step, cell sourcing, already raises important considerations around standardized protocols and starting material quality. Coordinating patient schedules or identifying suitable donors for allogeneic therapies are labor-intensive tasks, requiring specialized laboratory personnel and logistics teams. Once the starting material is obtained, the focus shifts to isolating the target cell population from a heterogeneous mixture (2).

To minimize impact on cell viability and functionality, the isolation method is frequently selected based on the cell type in question. Magnetic-activated cell sorting (MACS), which uses magnetic particles to bind cell surface markers, is widely employed in CAR-T cell preparation from leukapheresis samples at scale. Manufacturers may also opt for alternative approaches, as illustrated by density gradient centrifugation, fluorescence-activated cell sorting, or label-free separation (7). Cell activation and expansion then take place in the cultivation vessel of choice, supported by growth factor supplementation, such as bone morphogenetic protein 3 (BMP-3) and fibroblast growth factor 2 (FGF-2) in mesenchymal stem cell (MSC) proliferation.

Cell density, glucose and glutamine uptake, and dissolved oxygen are critical determinants of maintaining the desired cell phenotype. Without appropriate process optimization, insufficient cell yield or biological exhaustion are among the most visible consequences. With cells serving as both the architect and the active agent of the therapy, their potency and targeting precision can be further enhanced through engineering. Viral transduction is discussed in further detail later on, with a more novel and prominent tool represented by CRISPR/Cas gene editing. In 2024, Casgevy became the first CGT approved for manufacture using CRISPR/Cas technology, offering a one-time treatment for the lifelong condition, known as β-thalassemia (8).

Once the therapy product meets the defined critical quality attributes, which may range from specific marker expression to minimum viability thresholds, the most cost-intensive manufacturing steps are largely complete. Cell characterization throughout the entire CGT production process is central to ensure consistent morphological features, genotype, and functionality, relying on advanced, high-throughput analytical technologies. Prior to therapy administration and during transport, cell integrity remains supported through cryopreservation in liquid nitrogen at −130°C, with additional physical barriers preventing mechanical damage (2).

Regulatory accountaibility exists because the cost of getting it wrong is paid by patients

Delivering the engineered gene remains, for most therapies, a viral undertaking. Lentiviral vectors account for the largest share of approved ex vivo gene therapy manufacturing workflows, including 11 CAR-T products, while adeno-associated viral vectors dominate in vivo delivery. Non-viral routes, such as CRISPR/Cas editing, are steadily expanding the available options. What matters most from a manufacturing standpoint is less the mechanism itself than its downstream consequences. Because integrating vectors carry a long-tail safety profile, regulators now expect years of post-authorization follow-up and robust batch traceability — maintained through an unbroken chain of identity from cell collection to patient administration (9, 10, 11).

The reasoning behind these requirements is grounded in clinical data. Up to 90% of recipients of CD19-targeting CAR-T therapy products experience adverse effects, predominantly in the form of cytokine release syndrome. While CRISPR-Cas9-based editing may not engage the immune system to the same degree, unintended DNA damage and on-target genomic rearrangements observed in preclinical models remain to be fully resolved. Post-marketing surveillance and its findings can carry as much weight for clinical conclusions as for the underlying gene therapy manufacturing processes with tangible consequences for patient access (10, 11).

The obligations imposed by pharmacovigilance extend well beyond clinical registries tasked with tracking therapy recipients and capturing real-world effectiveness data. Manufacturers are also required to submit safety update reports to support ongoing risk-benefit assessments for each therapy agent. At the production level, challenges around reporting consistency and data harmonization can complicate downstream signal detection and analysis. These may appear to be operational concerns, but their consequences for patients awaiting life-saving treatment are significant — up to and including marketing authorization withdrawal and program shutdown due to failed reimbursement negotiations. Consequences of this kind can substantially set back therapy development or effectively nullify years of progress (12).

Yet, the latest advances in machine learning and automation offer meaningful tools to reduce the likelihood of such outcomes, supporting the robustness and continuity of cell therapy manufacturing processes at scale. When treated as a strategic asset from early development rather than an execution problem encountered late in the program, automated platforms can deliver substantial cost reductions, as demonstrated by Multiply Labs, which reported a 74% cost reduction in CGT scale-up manufacturing. While the risks inherent to viral delivery platforms cannot be eliminated entirely, embedding these strategies into commercial planning from the outset will help safeguard long-term therapeutic efficacy intertwined with patient outcomes (13).

Biologics cannot be rushed like generics, but optimized manufacturing can close the gap

Before examining what might accelerate CGT development going forward, there is value in addressing the broader GMP landscape beyond safety monitoring. The core principle requires that manufacturers control process variability, minimize contamination risk, and maintain supply chain integrity. Quality control and quality assurance are the two primary mechanisms through which these standards are upheld throughout cell therapy manufacturing. A cell-based assay evaluating transgene expression, for instance, is essential prior to large-scale cell expansion, while batch release testing, performed immediately before a therapy product enters the supply chain, verifies process consistency (14).

Where quality control focuses on the product itself, quality assurance addresses the prevention of systemic error. Assurance systems enforce real-time documentation of every batch-related activity, including chain-of-identity tracking from cell collection to patient administration. The integrity of living therapeutics is further supported by supplier auditing and corrective and preventive action protocols when deviations are identified. In these non-traditional manufacturing workflows, technical and operational barriers can emerge at every stage. Over time, biological variability and cellular heterogeneity translate into manufacturing concerns around process standardization and cost management (2).

Robust regulatory frameworks are non-negotiable in the development of safe and effective therapeutics, but their gradual harmonization could meaningfully encourage collaboration between established manufacturers and emerging therapy developers. The first allogeneic CAR-T therapy to reach market, for example, was brought forward by Catalent using a quality-by-design approach, delivering measurable cost and labor efficiencies for partner companies. In 2026, the FDA has also published draft guidance aimed at accelerating the CGT pathway from development to production, allowing chemistry, manufacturing, and controls (CMC) data to support earlier regulatory submissions (2, 15).

Further developments projected to accelerate the current state of CGT scale-up manufacturing are rooted in automated pipelines and fully digitalized platforms. From early-stage target selection — where AI is already being applied — to ensuring end-to-end data continuity, digital integration offers compelling support for the prerequisites outlined above (13). Automated platforms and machine learning are likewise gaining traction as tools for timely process optimization, particularly through closed, integrated manufacturing systems. These trends, alongside innovative solutions for adherent cell lines, are set to shape the industry’s long-term approach to CGT development (2).

Today’s position of advanced therapy manufacturing can be described as at a pivotal inflection point. The biological foundations are increasingly well-understood, regulatory frameworks are maturing, and landmark approvals from CAR-T therapies to CRISPR-based treatments have demonstrated what is clinically achievable. Yet, 74% of rejection letters issued by the FDA cite manufacturing or quality decisions as the rejection’s prime reason, demonstrating that scientifc promise will not work if not accompanied by strong and scale-ready CMC packages (16).

Closing the gap between validated biology and scalable, GMP-compliant production asks for deliberate investment in process infrastructure: closed bioprocessing systems, automated workflows, and digitalized quality management platforms that can accommodate the complexity of living therapeutics. Viral vector safety, batch traceability, and long-term pharmacovigilance are not peripheral considerations — they form the core to whether a therapy product reaches patients reliably and at scale. Consequently, the future of CGTs depends as much on how these therapies are manufactured as on what they are designed to do.

Conquering the development constraints in adherent cell lines with Archimedes® One

The focus of our dynamic adherent bioreactor, Archimedes® One, lies specifically in the design problems underlying cell therapy development. As the first system in a new category, the platform scales a range of adherent cell lines — HEK-293, Vero, and macrophages, enabling controlled and perfusion-based culture. Equipped with integrated process monitoring and automated harvest, the bioreactor delivers on the core functions, evidenced to accelerate scalable CGT production by this article. The provision of a standardized environment and consistent process throughput equally extend the tangible benefits, bringing manufacturing expediting from planning to the facility.

Learn more by exploring the Archimedes® One one-pager and the opportunities offered by Green Elephant Biotech’s Early Access Program.

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