Establishing GMP-compliant manufacturing frameworks for scalable allogeneic cell therapies

In this interview, experts Lisa Hamelmann (LH), Lucía Cespón (LC) and Iris Bischoff-Kont (IBK) from PromoCell (Heidelberg, Germany) experts share their valuable insights on how allogeneic cell therapies are driving the field forward, showing promise in clinical applications. They explore crucial considerations for maintaining cell quality, scaling up production and adhering to regulatory and Good Manufacturing Practice (GMP) requirements – key factors helping allogeneic therapies transition from bench to clinic for patients. 

This interview is part of the RegMedNet In Focus on allogeneic cell therapy. Discover expert opinions on this topic by visiting our feature homepage.

Which emerging allogeneic cell types, showing promise for clinical applications, do you think are worth keeping an eye on?

LH: We’re seeing exciting momentum in several allogeneic cell types beyond the “usual suspects” like CAR-T. Mesenchymal stromal cells (MSCs) continue to attract interest for their immunomodulatory properties, with expanding applications in autoimmune and inflammatory diseases. Also, in addition to well-established platforms like natural killer cells and iPSC-derived products, we’re seeing a growing interest in macrophage-based therapies.

Macrophages offer unique immunomodulatory and tissue-remodeling capabilities, making them highly relevant for oncology, fibrosis and regenerative medicine. Engineered macrophages can be tailored to enhance tumor targeting or support tissue repair.

Endothelial cells are also emerging as a focus for vascular regeneration and organ engineering. Meanwhile, fibroblasts—long considered “supporting actors”—are gaining recognition as active participants in wound healing, fibrosis modulation, and as potential delivery vehicles for therapeutic proteins. The expansion into these cell types reflects a broader trend toward leveraging specialized cell functions for targeted therapeutic applications, and it will require equally specialized manufacturing solutions to support their diverse growth and differentiation needs.

LCT: Beyond these, we also see growing interest in fibroblasts, keratinocytes and endothelial cells – cell types that are often overlooked but hold significant potential in regenerative medicine, wound healing and vascular repair. As a supplier of these primary cells and media optimized for their culture, we are closely following how they may be integrated into next-generation allogeneic therapies, either as standalone treatments or in combination with other cell types. Our focus is on supporting the field with high-quality, excipient GMP-grade culture media and reagents that are critical for maintaining cell quality, consistency and regulatory compliance throughout the development pipeline.

What needs to be considered to maintain cell quality in GMP environment, especially for allogeneic cell therapies?

IBK: Maintaining cell quality in a GMP environment requires careful consideration of a few factors, in particular cryopreservation. Cryopreservation plays an important role in allogeneic workflows enabling batch production, stockpiling and global distribution of allogeneic cell therapies. It enhances product shelf-life and allows for flexible clinical scheduling, decoupling manufacturing from administration.

What are the crucial considerations for cryopreservation to maintain a GMP environment?

IBK: Cryopreservation plays a vital role in enabling scalable and flexible production of allogeneic cell therapies. It allows for batch manufacturing, stockpiling and extended shelf life, which improves logistics and clinical scheduling by separating production from administration. This is especially important for regenerative medicine, where off-the-shelf availability and broad patient access are key advantages.

To ensure therapeutic cell quality in a GMP environment, the cryopreservation medium should be defined, animal component-free, and manufactured under GMP standards using traceable raw materials. It should preserve cell viability, identity and potency, particularly for sensitive cell types. Additionally, validated freezing protocols and controlled cryogenic storage with continuous monitoring are essential to maintain consistency and safety. GMP-compliant cryopreservation is indispensable for integrating allogeneic therapies into reliable, GMP-compliant workflows and advancing regenerative medicine toward clinical application.

What strategy would you recommend in scaling up allogeneic cell therapy production without compromising quality or consistency?

LH: Scalability should never come at the expense of product quality or batch-to-batch consistency. This means building robust, reproducible processes from the start and locking in high-quality GMP-grade media and reagents early on. The choice of a suitable cell culture medium is critical. Not only for cell growth, but for maintaining phenotype and functionality at scale. Also, media formulation choices matter at every step, as serum-free, xeno-free or ACF formulations reduce batch-to-batch drift and simplify regulatory comparability. Working with a supplier that offers both standardized Excipient GMP-grade formulations and Custom GMP Services can make a significant difference, as it allows the manufacturing process to be tailored to a cell type’s unique needs while still meeting stringent regulatory standards. This approach minimizes surprises during tech transfer and late-stage scale-up.

How important is the choice of culture media and reagents in the scaling-up process?

LH: The choice of culture media is critical – it directly influences cell growth, phenotype and therapeutic potency. Importantly, selecting the appropriate medium as early as the discovery phase lays the foundation for downstream success. It facilitates smoother process transfer, reduces the need for revalidation and supports regulatory alignment.

How early at the allogenic cell therapy development stage should researchers engage with experts to understand regulatory requirements and smooth bench-to-clinic transition?

LH: For allogeneic therapies, the best time to engage is as early as preclinical development—particularly when defining the culture media and process parameters for master cell bank production. In an allogeneic model, one manufacturing process will serve many patients, so changes later in development can trigger complex comparability studies across an entire batch history. Nutrient composition and the GMP status of excipients are critical here. Early expert input can prevent costly rework or delays in regulatory filings. It’s equally important to lock in raw-material traceability from the outset, covering media specification status, viral safety, and supplier qualifications, because regulators often request vendor audit summaries for materials used at large scale. Leveraging a Custom GMP Service at this stage ensures these technical and regulatory requirements are built in from the start, with much of the documentation and compliance burden handled by experienced partners.

LC: Researchers developing allogeneic cell therapies should engage with regulatory experts as early as possible in the development lifecycle, ideally during or just after proof-of-concept. This early engagement is critical to ensure a smooth transition from bench-to-clinic, and to align development strategies with regulatory expectations.

• Input from regulatory affairs experts at this stage helps to:
• Select appropriate raw materials and ensure proper documentation for future regulatory submissions
• Design scalable, compliant processes from the outset
• Navigate complex manufacturing and quality requirements
• De-risk innovation and investment
• Accelerate the transition from bench-to-clinic

How do you ensure GMP compliance and product consistency when transitioning from research-grade to clinical-grade allogeneic cell therapies?

LCT: The transition from research-grade to clinical-grade production is a complex and highly regulated process that requires careful planning and execution. The key is to map out GMP requirements early and align raw material specifications, documentation, and production processes with them before the switch. Working closely with experts allows developers to adapt existing protocols, qualify suppliers, and ensure that every reagent, including cell culture media, is compliant and fully documented.

For example, the use of Excipient GMP-grade cell culture media, which ensures that raw materials are manufactured and tested according to recognized standards such as EXCiPACT™ GMP certification. This provides assurance of consistent quality, stability, and performance throughout the scale-up process, and supports regulatory compliance.

By integrating these practices from the outset, developers can mitigate the risk of revalidating processes late in development, which can delay timelines and increase costs, while also ensuring product consistency and reliability as they move toward clinical-grade allogeneic cell therapies.

How do you see the field of allogeneic cell therapy evolving in the next 5–10 years, particularly in terms of combining different cell types or technologies?

IBK: The next decade will likely see a rise in multi-modal therapies, combining allogeneic cells with gene editing, biomaterials or biologics to enhance efficacy and targeting. We also anticipate:

• Increased use of induced pluripotent stem cell-derived cells for scalable, off-the-shelf solutions
• Integration of AI and automation in manufacturing and quality control
• Personalized allogeneic approaches, where donor cells are matched based on immunogenetics

LCT: As the field matures, we will see multi-cell therapies and next-generation platforms that tackle a broader range of diseases, making allogeneic cell therapies a cornerstone of modern medicine. We remain committed to supporting innovation with high-quality, GMP-compliant tools. These tools enable safe and effective therapies – from early research through to clinical and commercial manufacturing.

IBK: We’re moving toward a more modular, combinational future for allogeneic therapies. For example, combining MSCs with gene-edited macrophages, could address complex diseases with multi-pronged mechanisms of action. We’ll also see more integration with enabling technologies like gene editing, synthetic biology, and smart biomaterials. This will require manufacturing solutions that are both flexible and GMP-compliant, with the ability to adapt to diverse cell types and their unique culture requirements. In this landscape, having scalable, regulatory-ready raw materials and the ability to customize them will be a strategic advantage.

The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of RegMedNet or Taylor & Francis Group.

In association with PromoCell.