Basic concepts of exosomes and global regulatory framework
In recent years, the popularity of exosomes in the field of life sciences has continued to rise. Especially after this year's "315 Party", it has become the focus of attention of the whole society. As a practitioner in the field of cosmetics regulations and safety assessment, Odyssey Compliance Incorporation(OCI) Company would like to use this article to jointly clarify the basic concepts of exosomes with industry colleagues, and deeply explore their regulatory framework in major economies around the world, aiming to help companies clarify compliance boundaries and achieve steady development.
一、 Core concept: What are exosomes?
Exosomes were first discovered in sheep reticulocytes in 1983 and were officially named "exosomes" in 1987. Initially, scientists mistook exosomes as "waste" excreted by cells, but as research deepened, their value gradually became apparent. In 2013, the Nobel Prize Committee awarded the Prize in Physiology or Medicine to three scientists who discovered the regulatory mechanism of intracellular vesicle transport. As part of this complex transport system, research on exosomes has entered a fast lane. Its natural cell penetration, low immunogenicity, and potential in tissue repair, immune regulation, etc., make it a research hotspot in the fields of targeted drug delivery and other fields.
Simply put, exosomes are small vesicles secreted by living cells, with a diameter between 30 and 150 nanometers and a double-layer lipid membrane structure. It is widely present in our body, and its traces can be found in various body fluids such as peripheral blood, ascites, urine, saliva, and cerebrospinal fluid.
From the composition point of view, exosomes carry a lot of important information: lipids, proteins, nucleic acids.
Lipids: rich in cholesterol and sphingomyelin, which constitute the membrane structure of vesicles;
Proteins: including transmembrane proteins (such as CD9, CD63, CD81), heat shock proteins, metabolic enzymes, etc., some of which are markers of exosomes and are used for identification and isolation;
In terms of nucleic acids: they carry genetic information molecules such as mRNA, miRNA, circRNA, etc., and can transmit gene expression regulation signals.
How are exosomes formed? It originates from multivesicular bodies in cells. When the multivesicular bodies fuse with the cell membrane, the internal vesicles are released outside the cell and become exosomes.
To obtain highly pure exosomes, all cell debris and other impurities must be effectively removed. Currently commonly used extraction methods include ultracentrifugation, gradient centrifugation, magnetic bead immunoassay, ultrafiltration, polymer precipitation, etc. The purity and effective substance content of the products finally obtained by different extraction methods are particularly different.
After extraction, how do we judge whether the extracted exosomes are the ones we need? This involves how to identify exosomes? According to the proposal of the International Society for Extracellular Vesicles, there are three main markers for exosome identification:
The first is transmission electron microscopy, which is used to observe the shape and size, and directly observe the morphology of individual exosomes through negative staining. However, electron microscopy will have background interference and cannot distinguish exosomes from particles with similar shapes.
The second is particle size detection, which uses optical principles to sense the presence of particles and can detect the number and diameter of exosomes accurately, quickly, and with good repeatability. However, this method cannot confirm the true existence and integrity of exosomes and is not suitable for complex samples.
The third is Western blotting, which detects exosome marker proteins, such as CD63, TSG101, Alix, etc., through the specific binding of antigens and antibodies to identify exosomes from the protein level.
Of course, the development of exosomes in China is also very fast. We have also formulated corresponding inspection standards "Human Mesenchymal Stem Cell Exosome Preparation and Inspection Specifications". The identification requirements of the International Extracellular Vesicle Society are basically consistent with the requirements of our country's group standards.
The sources of exosomes are very diverse, including human sources, such as umbilical cord mesenchymal stem cells; plant sources, such as green tea and aloe extract; and animal sources, such as milk and salmon fibroblasts. Those with the same human origin also come from different cell sources. The composition of exosomes from different sources varies greatly, with different growth factor concentrations and active ingredient contents, resulting in uneven efficacy. Relatively speaking, the components of human-derived exosomes are relatively stable and highly active; the active ingredients of plant-derived exosomes fluctuate greatly; and those of animal-derived exosomes have biosafety risks and component complexity issues.
Biotechnology is booming, and a large number of such products have emerged. With products, we need to analyze and manage risks. If they are not managed, a lot of chaos will result.
二、China’s regulatory requirements for exosomes
In China, the application scope of exosomes is mainly concentrated in the three major fields of cosmetics, drugs and medicaldevices, but the regulatory paths and openness are completely different.
1、Cosmetics field: total ban
Currently, Chinese cosmetics regulations clearly prohibit the use of exosomes, especially human exosomes.
Core basis: The Prohibited Ingredients List (No. 387) of the "Technical Safety Specifications for Cosmetics" clearly stipulates that human tissues, cells or products of human origin are prohibited ingredients.
Key regulatory developments:
In 2022, market regulatory authorities in Guangdong, Zhongshan and other places successively issued documents warning that "exosome cosmetics" are commercial gimmicks.
In October 2022, the China Institute of Food and Drug Control (China Institute of Food and Drug Control) made it clear that "exosomes do not belong to the category of cosmetic raw materials." Any use of the "raw material submission code" to promote exosome cosmetics is suspected of false propaganda.
Original content: The raw material company or the cosmetics company designated by the raw material supplier completes the raw material safety information registration on the raw material platform and the platform generates the raw material submission code, which does not mean that the raw material has been approved or recognized by the regulatory department. Anyone who falsely claims that the raw material has been approved or recognized by the regulatory authorities by using similar terms such as "obtaining the raw material submission code" or even fabricating trade names such as "such and such exosomes" that do not fall within the scope of cosmetic raw materials for similar promotion is suspected of false or exaggerated publicity and will be investigated and punished by the relevant regulatory authorities in accordance with the law.
In January 2023, the "Technical Guiding Principles for Determination and Research of New Cosmetic Ingredients" for comments further clarified that exosomes, etc., do not belong to new cosmetic raw materials because their functions exceed the definition of cosmetics.
Original content: 4. Raw materials whose actual functions or objective effects exceed the definition of cosmetics. For example, raw materials with functions such as "activating cells", "regenerating cells", "reducing pigmentation at wound sites", "promoting healing", "promoting heavy metal efflux", and "anti-aging"; biological factors (proteins or peptides, etc.) from various sources that have the activity of promoting cell or tissue proliferation, such as epidermal growth factor (EGF), fibroblast growth factor long factor (FGF), insulin growth factor-2 (IGF-2), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF), transforming growth factor β1 (TGF-β1), etc.; others such as exosomes, stem cell-derived raw materials, etc.
In August 2024, in its reply letter to the CPPCC proposal, the State Food and Drug Administration once again emphasized the international community's cautious attitude towards the use of human-derived substances in cosmetics, and cited relevant regulations of the European Union, Japan, and South Korea as evidence.
Original content: At present, the world's major cosmetics producing countries and regions are cautious about the use of human-derived substances in cosmetics. For example, in the EU's cosmetics regulations, the list of prohibited substances includes human cells, tissues or products; Japan prohibits extracts from tissues such as human placenta; South Korea also lists human cells, tissues and their culture media as prohibited raw materials.
In summary, within the territory of our country (unless otherwise specified in Taiwan), any cosmetics that claim to contain exosomes are illegal.
2、Drug field: included in supervision, research first
Compared with the strict prohibition in the cosmetics field, the pharmaceutical field attaches equal importance to scientific research and prudent supervision of exosomes.
Key regulatory developments:
In June 2025, the Drug Evaluation Center of the National Medical Products Administration issued a draft for comments on the "Scope, Classification and Interpretation of Advanced Therapeutic Drugs", officially including exosomes and their derivatives within the regulatory scope of advanced therapeutic drugs and classifying them as "new delivery system drugs" or "cell derivative drugs".
Original content: New delivery system drugs: Generally speaking, in addition to drugs that are used to deliver genetic material belonging to GTMP, other delivery system drugs are based on innovative technologies such as microorganisms, cells or genetic engineering to construct carriers and are used to deliver active ingredients. The realization of their functions is closely related to the innovative design and preparation of the delivery carrier. For example, drugs using cell carriers, organelles, vesicle carriers (such as extracellular vesicle carriers), etc., can contain non-genetic materials such as proteins, active peptides, or small molecules.
Cell derivative drugs: generally refer to drugs that use substances produced or secreted by cells as active ingredients. Their active ingredients include organelles, extracellular vesicles, platelets, etc.
In July 2025, the CCPC included exosomes into the testing scope for the first time in relevant questions and answers.
At present, the relevant guiding principles are still in the stage of soliciting opinions, and the drug research and development cycle is long. There will be no successful registration of exosome drugs in the short term.
3、Medical device field: boundary exploration
Key regulatory developments:
In October 2024, the Central People's Procuratorate of China listed stem cell exosomes in the category of "products not recommended to be regulated as medical devices".
In December 2025, the latest classification definition results showed that a "sodium hyaluronate exosome membrane liquid dressing" was recommended to be classified as a drug-device combination product.
Original content: "Sodium Hyaluronate Exosome Membrane Liquid Dressing" consists of freeze-dried powder A (composed of exosome membrane, phosphate buffer, sodium chloride, poloxamer 188) and diluent B (composed of purified water, phosphate, sodium chloride, sodium hyaluronate). The exosome membrane is composed of "protein, sodium chloride, peptides, phospholipids, disodium edetate and water". Supplied non-sterile. When using, mix freeze-dried powder A and diluent B to form a liquid and apply it to the wound surface. On the one hand, it is claimed that it acts as a physical barrier by forming a protective layer on the surface of the wound. On the other hand, the exosome membrane contained in the product contains "proteins and peptides" that may exert biological activity when exposed to the wound (polypeptides may promote the regeneration of wound blood vessels, accelerate the healing of deep skin wounds, inhibit inflammatory reactions and other biological activities; proteins can repair damaged tissues by synthesizing new cells). Claimed to be used for the care of small wounds, abrasions, cuts, non-chronic wounds and surrounding skin.
It is worth noting that the component of this product is "exosome membrane" rather than complete exosomes. This case provides a new exploration direction for the classification of exosome-related products as medical devices, but it is still unclear whether exosomes themselves can be applied for under this route.
4. Taiwan, China: Conditional opening
On March 21, 2024, the Food and Drug Administration of Taiwan's Ministry of Health and Welfare issued regulations to revise the "List of Prohibited Ingredients in Cosmetics" and added a description of restrictions on human cells, tissues or human-derived products. However, it is also stipulated that the use of exosomes from human cells will no longer be subject to this restriction if the case application is approved by the competent authority.
On February 2, 2026, Taiwan issued a revised review document and it officially came into effect.
Currently, there is a case in Taiwan Province in which human umbilical cord mesenchymal stem cell exosomes have been approved as cosmetic ingredients by the Ministry of Health and Welfare. Xunlian Biotechnology is the first company in Taiwan to obtain the human-derived exosome cosmetics license from the Ministry of Health and Welfare.
To summarize: In my country, except for Taiwan, any exosomes are prohibited from being used in cosmetics; drugs and medical devices are also in the research stage, and no products can be actually used in drugs and medical devices.
三、 Regulatory requirements of the world’s major economies
The regulation of exosomes in the world's major economies focuses on human-derived exosomes, while there are relatively few restrictions on animal and plant sources.
1、United States
The US FDA's supervision of stem cell exosomes is mainly based on the Public Health Service Act and the Federal Food, Drug and Cosmetic Act. The Cell Therapy Products Office under the Center for Biological Products Evaluation and Research is specifically responsible for the technical review work.
The FDA mainly classifies stem cell exosome products as "human cells, tissues, and cell- and tissue-based products." Then different regulatory paths are divided according to the degree of risk:
Path 351: Applicable to exosomes that have been significantly processed, used non-homologously, or used in combination with other products, and a biological products license application needs to be submitted;
361 Path: Exosomes that are limited to autologous or first-degree relative sources, have undergone minimal manipulation and are used for homologous local treatment, can be exempted from pre-market approval, but must meet relevant quality standards;
IND path: Exosomes in the clinical trial stage need to submit an investigational new drug application. In 2022, the FDA will clearly require donor screening records, exosome marker data and functional potency testing methods.
2、Europe
The European Medicines Agency has included stem cell exosome products in the "advanced therapeutic medical products" framework for supervision. The Advanced Therapeutic Products Committee is the core organization for exosome product review. Responsible for scientific assessment and technical consultation.
EMAs are classified according to their mechanism of action:
Gene therapy products: suitable for exosomes carrying exogenous genes;
Somatic cell therapy products: suitable for exosomes that directly regulate cell function through secreted factors;
Composite advanced therapy products: Applicable only when exosomes and medical devices form a single integrated product, such as coated stents.
If the classification is unclear, EMA has also established a "borderline product" assessment procedure to determine the final regulatory path.
3、Japan
The Japan Pharmaceuticals and Medical Devices Agency (PMDA) classifies exosomes as specific cell processed products in accordance with the "Regenerative Medicine and Other Products Safety Assurance Act". The Regenerative Medical Products Office conducts a technical review, and the Ministry of Health, Labor and Welfare (MHLW) makes an administrative licensing decision.
The Japan Pharmaceuticals and Medical Devices Agency adopts a triple regulatory collaborative supervision model for stem cell exosome products: Its supervision adopts a triple regulatory collaborative model:
The first is the path of the "Drug and Medical Device Law", which is applicable to products produced in industrial production and commercial circulation and must comply with GCTP standards;
The second is the path of the "Regenerative Medicine Safety Assurance Act", which is applicable to medical institutions for self-use or clinical research and must comply with GCP regulations;
The third is the path of the "Clinical Research Act", which is applicable to exploratory research by scientific research institutions and requires approval by the institutional review board.
In addition, under the Regenerative Medicine Safety Assurance Act, a hierarchical management mechanism based on risk levels has been established to adopt differentiated regulatory measures for different risk levels.
Category 1 (high risk): Exosome products involving genetic modification/allogeneic sources require direct approval from the comprehensive pharmaceutical and medical device agency (application materials include non-clinical pharmacology and toxicology data);
Category II (medium risk): natural exosomes with new routes of administration, reviewed by designated certified medical institutions (≥10 pilot clinical safety data need to be submitted);
Category III (low risk): Exosome preparations derived from autologous sources and applied locally are subject to a filing system (need to comply with the "Medical Technology Implementation Regulations")
4、South Korea
Medical field: managed according to "regenerative medicine preparations", relatively flexible.
Regulatory agency: MFDS (Ministry of Food and Drug Safety).
Legal basis: "Regenerative Medicine and Other Products Safety Assurance Act."
Classification: Human exosomes are defined as Regenerative Medicine Products.
Approval features: Implement hierarchical management, allowing conditional approval (Conditional Approval): Before completing confirmatory clinical trials, if preliminary data show safety and possible effectiveness, provisional approval for marketing (valid for 3 years, can be extended) can be obtained, during which real clinical data must be collected.
Conclusion and outlook
As of now, no exosome drugs or injection products have been officially approved for marketing in the world. Its mechanism of action, standardized preparation process, safety and effectiveness still need to be verified by a large amount of scientific research. The research potential of the laboratory does not equal the mature clinical application. Any product claiming that exosomes can "cure all diseases" or have "anti-aging effects" is false propaganda.
Real exosome research and development must follow a rigorous scientific path and undergo long-term clinical trials and strict safety assessments. With the continuous deepening of basic research and translational medicine, the regulatory system for exosomes will also become increasingly perfect in the future. Odyssey Compliance Incorporation(OCI) Company will continue to pay attention to global regulatory developments and provide industry partners with timely and professional compliance interpretation and support.
