Standardized Preparation and Inspection of Extracellular Vesicles

According to incomplete statistics, there are currently 264 clinical trials worldwide related to extracellular vesicle therapy and diagnosis. Clinical indications for drug therapy include solid tumors, osteoarthritis, bladder cancer, hepatocellular carcinoma, lung injury, diabetes, and more. Additionally, extracellular vesicles can serve as "natural nanoparticles" for drug delivery, offering vast application prospects.

However, even minor variations in production conditions can significantly affect the quality and activity of extracellular vesicle products. Therefore, establishing comprehensive and unified industry standards for the preparation and testing of extracellular vesicles is of great significance for promoting the industrial development of extracellular vesicle research and applications.

On February 3, 2024, the China Food and Drug Enterprises Quality and Safety Promotion Association issued an announcement. The "Standardization for the Preparation and Inspection of Human Mesenchymal Stem Cell-Derived Extracellular Vesicles" (hereinafter referred to as the "Standard"), organized and compiled primarily by Beijing CytoNiche Biotechnology Co., Ltd. (hereinafter referred to as "CytoNiche"), was officially released. The Standard will be implemented starting from March 6, 2024.

Founded by Dr. Liu Weibo, CEO, Dr. Yan Xiaojun, CTO, and Dr. Sun Yanxun, Vice President, CytoNiche, with their outstanding technical capabilities, actively participated in data collection, determination of technical parameters, experimental verification, and drafting of the standard.

Standard Development

This standard was jointly developed by numerous national enterprises and institutions over a period of more than 1 year and 4 months. It complies with the regulations of the "Group Standard Management Regulations" and the "Group Standard Management Measures of China Food and Drug Enterprises Quality and Safety Promotion Association", and was approved and released by the China Food and Drug Enterprises Quality and Safety Promotion Association as the coordinating unit.

The establishment and release of this standard signify the transition of the development and commercialization of human mesenchymal stem cell-derived extracellular vesicle technology from individual enterprise behavior to industry standardization, institutionalization, and normalization. This also indicates that, under the guidance and support of relevant policies such as the national "14th Five-Year Plan" for development, the biocell industry will have a clear direction and solid foundation for future development, thus ushering in a new stage.

CytoNiche, with its mature technology and products for the large-scale production and preparation of extracellular vesicles, as well as its rich experience in the 3D FloTrix® Cell Technology Platform - stem cell and extracellular vesicle quality detection platform, participated in the formulation of this standard. This move further demonstrates CytoNiche's leadership in the field of three-dimensional cell culture and its commitment to promoting industry standardization, leading the development of the cell and gene therapy industry.

Interpretation of the Standard

CytoNiche can provide large-scale mesenchymal stem cell-derived extracellular vesicle production support that meets the requirements of the standard according to different customer needs:

● 3D FloTrix® Cell Technology Platform - Large-scale Mesenchymal Stem Cell-Derived Extracellular Vesicle Preparation

● Customized Solutions for Large-scale Extracellular Vesicle Production Preparation - Process Technology & Products
 

CytoNiche's Overall Advantages in Large-scale Cell & Extracellular Vesicle Production Preparation:

1. 3D Biomimetic Cultivation:
   Recreates the growth microenvironment of cells in the human body, promoting the secretion of high-quality extracellular vesicles.

2. Short Single Batch Production Cycle:
   4-5 days, with the potential to produce up to 30L of cell culture supernatant.

3. Direct Connection between vivaSPIN and vivaEXO:
   Enables rapid processing of fresh cell culture supernatant.

4. Dual Approach, Emphasizing Quality and Efficiency:
   Allows for the collection of both cell culture supernatant for extracellular vesicle harvesting and cells, meeting the requirements for cell and extracellular vesicle quality inspection.

Extracellular Vesicles Produced at Large Scale through CytoNiche's 3D FloTrix® Process Meet the Key Quality Attributes Required by the Standard:

Morphology TEM: Exhibits clear membrane structures, displaying a classic"cup-shaped" morphology.

Particle Size NTA: Particle size distribution falls within the range of 30-150nm, with distinct peaks.

Marker Proteins WB: Expresses TSG101/CD63/CD9/CD81, does not express Calnexin.

CytoNiche can provide various testing services compliant with the standard:

● 3D FloTrix® Cell Technology Platform - Stem Cell and Extracellular Vesicle Quality Testing

Industry Leading

CytoNiche has developed and produced a series of customized microcarriers, combined with self-developed equipment products, to establish a 3D cell intelligent manufacturing platform. With various bioreactors in place and complemented by harvesting and packaging systems, efficient large-scale cultivation, harvesting, washing, concentration, and packaging of 3D cells and extracellular vesicles can be achieved. Through automated, continuous, and closed production pipelines, various risks of contamination associated with open operations are mitigated.

By meeting the clinical application standards for the quality and safety of cell and extracellular vesicle therapy products, CytoNiche can also meet the demands for cell and extracellular vesicle production during clinical application and commercialization processes.

[About CytoNiche]

CytoNiche was established in 2018, led by Professor Yanan Du's research team from the School of Medicine at Tsinghua University, with Tsinghua University as a shareholder. The core technology originated from the transformation of scientific achievements at Tsinghua University and was recognized as a leading technology in "Science and Technology Innovation in China" by the China Association for Science and Technology. As a national-level high-tech enterprise, a national-level specialized and new technology "Little Giant" enterprise, a potential unicorn enterprise, it has also received key research and development special support from the Ministry of Science and Technology.

As an expert in high-quality three-dimensional cell manufacturing, CytoNiche provides a one-stop customized solution for cell scale-up based on 3D microcarriers. The company has built an original 3D cell smart manufacturing platform, achieving large-scale, automated, intelligent, and closed-cell drug and derivative production preparation. This helps global customers establish the most advanced cell drug production lines. After pioneering the production process pipeline for "billion-level" stem cells, the company is accelerating towards "hundred billion-level," dedicating efforts to empower the cell and gene therapy industry with 3D cell scale-up smart manufacturing technology to benefit more patients.