Inside the Exosome Boom: Global Experts Talk Industry Trends, Roadblocks, and What’s Next

The symposium “Challenges and Regulations of Extracellular Vesicles in Clinical Development” successfully brought together leading voices from academia, industry, and policy to explore the evolving landscape of extracellular vesicle (EV) and exosome research. Co-hosted by key institutions from Taiwan and Japan, the event served as a dynamic platform for cross-border dialogue, highlighting regulatory hurdles, emerging opportunities, and innovative strategies shaping the future of EV-based clinical applications. As international interest in EV and exosome technologies continues to accelerate—particularly in areas such as diagnostics, therapeutics, and drug delivery—the insights shared at this symposium offer timely relevance to stakeholders navigating this rapidly advancing global field.

Microtherapy and Bioreactors Lead the Charge

Mass production of EVs remains a key bottleneck in bringing cell-free therapies to the clinic. The panel opened with strong emphasis on microtherapies, with bioreactors being spotlighted as central to this effort. These dynamic, fluid environments partially mimic in vivo and in situ conditions, allowing cells to attach and grow more efficiently. Preparing such systems for tech transfer to CDMOs (Contract Development and Manufacturing Organizations) is already underway, but the technology still faces scalability concerns.

EVs can be roughly divided by size and origin—some are broad-spectrum secretions from multiple cells, others are engineered through biogenetic modification, and a third category involves minimal alterations. Engineering strategies include applying mechanical stress, introducing reagents, or altering cell environments. However, the big question remains: are these EVs still functionally equivalent? Companies leveraging EVs as delivery carriers, especially in mRNA therapies, must ensure their therapeutic cargo remains effective while scaling.

From 2D to 3D: Production Strategies Depend on Cell Type

When scaling EV production, the cell source matters. Manufacturing using established protein-expressing cell lines (like those used for viral vectors) is relatively straightforward. However, producing primary cells at scale poses greater challenges. In lab conditions, yields are low—often limited to 20–30 units of supernatant. Transitioning to microcarrier beads or 3D cultures, such as mesenchymal stem cells (MSCs), can boost EV secretion by up to fivefold.

But that comes at a cost. The EVs from 3D systems can differ in quality compared to traditional 2D ones, raising concerns about consistency and mode of action. Ultimately, scalability hinges on tailoring the approach to the specific cell type, intended modality, and end-use—whether in academia, pharma, or clinical-grade product development.

Safety First: Immune Reactions, Tumorigenicity, and Biomarkers

As EVs move closer to clinical application, safety remains a top concern. One panelist pointed out the need to study immune responses triggered by non-naïve EVs, especially when tumorigenic cells are involved. For many, exosomes—a purified subset of EVs—are preferred over whole supernatant due to clearer activity profiles. Still, characterizing the “active ingredient” within EVs remains a scientific hurdle.

In Japan, regulators are leaning toward applying the same safety standards used for cell-based therapies to EV products. But some panelists cautioned against overregulation, advocating for minimal and precise requirements. Continuous dialogue between academia and industry is necessary, as safety tends to be case-specific. Clearer guidance, like Japan’s recent CMC (Chemistry, Manufacturing, and Controls) publication, is welcomed, but more detailed frameworks are needed.

Clinical Applications: Start Small, Target Rare

EV-based therapies differ drastically from conventional drugs, especially in how they interact with the body. Many agreed that targeting rare diseases—where few therapeutic options exist—is the best path forward. Interstitial pulmonary fibrosis (IPF), for instance, was cited as a key example where EVs could fill a serious clinical gap.

Defining appropriate clinical endpoints and APIs (active pharmaceutical ingredients) remains murky. Exosomes are often described as “cargo carriers” with therapeutic potential, but their content varies. Engineered exosomes, such as those designed to deliver mRNA, may help improve clinical translation and market access. The panel stressed that effective communication and education for both clinicians and patients is crucial for adoption.

Anti-Aging and Regulatory Tightropes

A hot-button issue emerged when the discussion turned to EV products marketed for anti-aging. Panelists agreed that aging is a physiological process, not a disease, making it an inappropriate target for medical claims. In Taiwan and Japan, regulations strongly prohibit misleading advertisements, with websites being shut down if found in violation—though penalties remain minimal.

That said, some experts acknowledged that EVs could play a role in supporting health and well-being. Still, clinical trials must differentiate between natural aging and pathological aging (e.g., progeria). This distinction is essential for regulatory approval. Evidence-based claims, not marketing trends, should guide product development. The consensus? Enrolling in well-designed clinical trials is the most responsible path forward.

The CDMO Gap: From Academia to Industry

A recurring theme was the critical role of CDMOs in advancing EV therapies. Yet, most CDMOs lack early-stage expertise, particularly in upstream processes. The technology transfer from academia to production partners needs more support and funding. Experts recommended focusing on a single lead product to streamline development and validate manufacturing approaches.

From a biotech perspective, securing GMP-grade donor cells and intellectual property is essential. Standardizing purification techniques is easier; scaling bioreactor processes, however, remains capital-intensive. Immortalized cells offer scalability but come with tumorigenicity concerns. Long-term safety and repeat dosing studies are needed to assess potential risks.

One notable gap is the industry’s limited ability to analyze, quantify, or even define EVs consistently. Without a standardized approach to characterization, it’s difficult to develop robust regulatory strategies. Several panelists called for better data sharing and collaborative infrastructure between academia, biotech startups, CDMOs, and regulators.

Looking Ahead: Trials, Trust, and Transparency

The path forward will likely be slow but steady. Japan, for instance, is waiting on U.S. regulatory direction before formalizing its own EV-specific guidelines. Preclinical development dominates the landscape for now, but once clinical-stage programs break through—like those led by Fujita—others are expected to follow quickly.

The panel closed with a call to action: foster better public understanding, support evidence-based development, and invest in partnerships that span the full product lifecycle. EVs may be complex, but with the right infrastructure and collaborative spirit, their promise as next-gen therapeutics remains within reach.

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Author

Bernice Lottering