Yocon Interpretation | Guiding Principles for Pharmaceutical Research and Evaluation of Human-Derived Stem Cell Products (Trial)

Zhang Yiping


Company Events

On April 27, 2023, the Drug Evaluation Center of the National Drug Administration issued the "Guidelines for Pharmaceutical Research and Evaluation of Human Derived Stem Cell Products (Trial)", abbreviated as the "Guidelines". The release of this document provides standardized guidance for the pharmaceutical research and production of stem cell products.

This article will interpret the above "Guidelines" from aspects such as stem cell culture, requirements for raw and auxiliary materials, and cell quality testing, fully demonstrating the important role of GMP-grade products in meeting the requirements of the Guidelines and promoting stem cell drug declaration.


1 The training process requires strict requirements

The "Guidelines" mentioned that human/animal-derived materials may have to be added during the cell culture process, and there is a risk of contamination and cross-contamination of exogenous factors that may be introduced during the operation process. For heterologous products, it is even more important to pay attention to the risk of introducing or spreading exogenous factors.


The most important production material to be added in the process of stem cell culture is the culture medium. Unlike traditional drug production materials, the culture medium has a certain modification effect on the cells themselves. A culture medium suitable for drug application can greatly reduce the workload of indication development and quality control from the source, Therefore, serum-free culture media with completely limited levels of ingredients can greatly reduce the risk of pollution and the introduction of exogenous factors, fully meeting the needs of the stem cell industry to develop new drugs.

The GMP grade mesenchymal stem cell serum-free culture medium developed by Yocon further removes complex protein types without adding serum or serum substitutes, making all its components necessary for stem cell growth, with a content of less than 1.5mg/mL. It conforms to the principles of clear composition and necessary composition in clinical evaluation guidelines and is a strict CD culture medium.


Not only do we need to control the raw materials during cell culture, but we also need to prevent the addition of harmful substances during cell cryopreservation. You Kang's GMP-grade vitrified cell cryopreservation solution is used in combination with a GMP-grade culture medium. This frozen storage solution is serum-free, protein-free, and DMSO-free. All components are completely clear, and there is no need for programmed cooling. It is easy to operate and has lower transportation costs.


2 Raw and auxiliary materials are safe and reliable

The Guidance points out that production materials include all raw materials, auxiliary materials, consumables, etc. used in the production process, and their sources and quality should be clear and reliable. The risk of introducing or spreading exogenous factors from production materials should be controlled to the maximum extent possible. Material suppliers and contract manufacturers should be evaluated and audited, and the responsible parties should be identified to ensure material quality.

The quality of raw materials is directly related to the quality of the final product. Risk assessment and quality control based on scientific and risk-based principles should comply with the requirements of the current version of the Chinese Pharmacopoeia "Quality Control of Raw Materials and Excipients for Biological Product Production" and "Preparation and Quality Control of Animal Cell Matrix for Biological Product Production and Testing".

It is necessary to fully consider the scientific and safe use of raw materials, as well as the continuous accessibility during large-scale production. The raw materials used in production should have a clear source, composition, usage, and quality control, and have documents such as raw material source certificate inspection report, packaging instructions, TSE/BSE risk analysis, etc. It is recommended to give priority to raw materials with high-quality standards and low-risk levels. If research-grade reagents (such as culture media, cytokines, small chemical molecules, etc.) are used in production, they should be produced according to GMP requirements as far as possible to ensure product consistency and purity.


The "Guidelines" clearly state that in order to ensure product consistency and purity, production should be carried out as much as possible in accordance with GMP requirements. Therefore, raw materials should also be used as much as possible in accordance with GMP requirements to achieve true safety in the establishment of cell banks during the drug reporting process.

In terms of the production environment, GMP grade mesenchymal stem cell serum-free culture medium is fully produced at the Yocon Miyun GMP grade production base. The culture medium filling area of this base is fully constructed in the B+A level background area of drug production, introducing the world's top automated filling production line and management system. The filling capacity reaches 2000L/batch, and at the same time, only one drug declaration grade reagent product is produced on a GMP-level production line, strictly prohibiting cross-production.


3 Strict control of cell quality

The "Guidelines" mentioned that the clinical trial application stage needs to meet safety requirements, and the preparation of samples should comply with the requirements of the "Good Manufacturing Practice for Drugs - Appendix for Clinical Trial Drugs"; Continue to improve production processes and product quality related research during clinical trials; Provide complete research data supporting product safety, effectiveness, and quality control when applying for listing.

The quality standard items of stem cell products generally include cell identification, cell activity (cell viability, number of living cells, number of functional cells, population doubling time), purity (such as target cell ratio), biological activity (such as differentiation efficiency, quantitative/semi-quantitative functional testing, biomarkers), product and process related impurities, tumorigenicity/tumorigenicity (if applicable), unexpected differentiation Microbial safety (sterility, endotoxin, mycoplasma, internal and external viruses), general testing (appearance, pH value, obvious foreign matters, osmotic pressure molar concentration, loading capacity), etc.


As an active drug, cells must ensure that the quality of every dose of cells entering clinical practice is reliable, and the first step in ensuring the safety of stem cell drugs is the culture medium. The culture medium has a certain modifying effect on cells. Cells cultured in Youkang GMP grade mesenchymal stem cell serum-free culture medium fully comply with industry standards in terms of cell morphology, surface marker identification, three-line differentiation ability, immune suppression, and regulation ability, tumorigenesis and tumorigenicity detection, etc. Under any process or cell itself without modification, the biological potential of cells still exhibits very good performance, I believe that downstream users can achieve the greater biological potential of stem cells by optimizing the cultivation process and delivery carriers. (Read the original text to view the development of a metaverse collection using GMP grade MSC serum-free culture medium)


With the continuous improvement of industry policies and guidance, it is believed that China's stem cell medical industry will also develop better, and many pharmaceutical companies will continue to emerge in the application of stem cell drugs. As an upstream supplier in the stem cell industry, Youkang will continue to break through and provide users with higher quality products, becoming a solid backing for users!


Constituent limited-level culture medium will welcome a bright future.