In the rapidly evolving landscape of advanced therapies, few challenges are as complex — or as consequential — as scaling cell therapy manufacturing to meet growing clinical and commercial demand. In this expert analysis, the team at AGC Biologics shares their perspective on the current state of the industry, the technologies shaping its future, and the barriers that must be overcome to make these life-changing treatments more accessible.
AGC Biologics brings firsthand experience to this conversation: the team played a pivotal role in achieving the first-ever FDA approval of a gene therapy for early-onset metachromatic leukodystrophy (MLD), Orchard Therapeutics’ Lenmeldy™ a milestone that underscores the real-world impact of getting manufacturing right.
How can you standardize the cell therapy manufacturing process?
Cell therapies represent a proven and powerful therapeutic approach with the potential to address a wide range of life-threatening diseases. While each product carries its own unique biological characteristics and clinical requirements, the underlying manufacturing logic follows a common modular framework that can be tailored to different cell types and therapeutic needs.
For developers looking to optimize their production processes, the following core steps form the backbone of most cell therapy manufacturing workflows:
- Starting material processing: Depending on the target drug product (DP), either fresh or cryopreserved biological cellular material may be used. Autologous products require patient-specific starting material for each batch, while allogeneic products allow multiple DP batches to be derived from a single healthy donor. Starting material may be used directly or following selection of specific cellular sub-populations.
- Cell activation: Stimulating cells to prepare them for subsequent processing steps.
- Genetic modification: The four primary approaches include gene replacement (restoring function by delivering a working copy of a defective gene), gene silencing (inactivating a toxic mutated gene), gene addition (introducing an exogenous gene to influence cellular behavior), and gene editing (making permanent, targeted changes to a patient's genome).
- Cell expansion: Scaling cell populations to the volumes required for clinical or commercial use.
- Drug product formulation and fill & finish: Preparing the final product for administration, including formulation, filling, and packaging.
Starting from this flexible common workflow, each step can be adapted to support a wide spectrum of manufacturing requirements, from early-stage development through large-scale commercial production.
What technologies or processes need to be optimized to overcome the key manufacturing challenges in cell therapy?
Many manufacturing processes, particularly at early-stages of development, depend on open handling steps that are labor-intensive and prone to human error. Moving to closed, automated systems remains an important goal for cell therapy production to reduce contamination risk, production costs, and timelines, while improving reproducibility. The market offers various automated platforms for these therapies, some provide complete, fully closed solutions, while others are modular, performing specific steps and integrating with other technologies.
However, several challenges remain before these systems can be universally adopted:
- Volume sensitivity: Automated devices can lose accuracy when processing small volumes, which is a critical limitation for autologous applications.
- Scalability: For allogeneic production, ensuring that automated systems can scale to meet large-batch manufacturing demands has remained a significant hurdle over the last several years.
- Flexibility and usability: Some platforms lack the adaptability needed to accommodate diverse process workflows and are not sufficiently user-friendly for routine GMP environments.
- Regulatory compliance: Newer devices entering the cell therapy space must still demonstrate full compliance with current Good Manufacturing Practice (cGMP) requirements before they can be reliably deployed in commercial production.
Addressing these gaps will be essential to unlocking the full potential of automation in cell therapy manufacturing.
What is AGC Biologics currently focused on in the cell therapy space?
Cell therapy processes are complex and vary by cell type, scale, reagents, equipment, testing, and design, depending on application (autologous or allogeneic) and whether they involve modification, expansion, or both. AGC Biologics aims to provide flexible, end-to-end services across all product lifecycle stages, from pre-clinical to commercial. Our support spans two global sites: our Milan Cell and Gene Center of Excellence and our new Yokohama, Japan facility, equipped to handle full development and manufacturing needs. Our expert teams have extensive experience in open and closed processes, equipment platforms, and viral transduction, and are constantly integrating new technologies to stay at the leading edge of innovation.
Our viral vector and cell therapy platform supports multiple cell types — including hematopoietic stem cells (HSCs), T-cells, CAR-T cells, NK cells, and mesenchymal stem cells (MSCs) — at scales appropriate for both autologous and allogeneic production. All process development (PD) activities are conducted under a GMP-like approach, enabling a smoother, lower-risk transition to full GMP manufacturing. Rounding out our offering is a suite of more than 160 in-house analytical tests, enabling comprehensive characterization of cell therapy products across all development and manufacturing phases.
Where does cell therapy go next, and how can developers prepare for the next phase of the industry?
The prohibitive price of cell therapies, driven by complex, individualized manufacturing processes, remains one of the most significant barriers to widespread patient access. Addressing this will require a concerted shift toward greater process standardization and broader adoption of allogeneic manufacturing models, which offer inherently better economies of scale.
At AGC Biologics, we are addressing both challenges by developing more standardized workflows and constantly innovating to make cell therapy production more efficient, scalable, and ultimately more affordable to produce, expanding access for the patients who need these treatments most.
With process development operations already available, the new facility in Yokohama, Japan brings with it the backing of a global supply chain network and one of the most experienced cell and gene scientific and manufacturing teams in the industry. It is all driven by the science and history of the central engine for AGC Biologics’ cell and gene CDMO services – the Milan site boasts a proud 30-year history in cell and gene therapy, 15+ commercial approvals and hundreds of successful GMP batches produced, this team of experts is using that proven track record to establish a new hub for cell therapy production in Japan.
From vector production to exciting local projects like exosome research with Jikei University, AGC Biologics’ CGT group possesses a deep understanding of Japan’s growing cell and gene industry, combined with a level of expertise few others can match. Additionally, the adjacent AGC Life Science building at the Yokohama Technical Center, home to over 1,000 scientists working on cutting-edge techniques and technologies, adds a powerful mix of knowledge, innovation, and technological strength that is hard to find elsewhere in the region.
Since process development services launched the teams in Milan and Yokohama have been collaborating on elements such as tech transfer steps, process documentation, test runs with T-cell products (including selection and transduction), global quality service to address FDA, EMA and PDMA requirements, among others, and establishing bilingual protocols to address global needs at this new state of the art Cell Therapy production site. GMP production will be available in 2027.
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