The Comprehensive Affairs Department of NMPA Solicits Public Comments on “Good Manufacturing Practice (GMP) – Appendix for Cellular Therapy Drugs (Draft for Comments)”

Chapter 1 Scope

Article 1 [Scope] The cell therapy products (hereinafter referred to as cell products) described in this appendix refer to living cell products of human origin, including cells that have been or have not been genetically modified, such as autologous or allogeneic immune cells, stem cells, tissue cells or cell lines, etc., but do not include blood components for transfusion, hematopoietic stem cells for transplantation that have been specified, reproductive-related cells, and tissue and organ products composed of cells.

Article 2 [Scope of Application] This appendix applies to the entire process of cell products from the transportation, receipt, production and inspection of donor materials to the release, storage and transportation of finished products.

The production, inspection and release of genetically modified vectors or other starting biological materials (including: viruses, plasmids, RNA, antigenic peptides, antigenic proteins, protein-RNA complexes, etc.) directly used in the production of cell products shall comply with the requirements of the current version of the "Good Manufacturing Practice for Pharmaceuticals" and its relevant appendices as well as this appendix.

Article 3 [General Requirements] Since the donor materials of cell products are derived from the human body, their production shall also comply with relevant national regulations to prevent the introduction or spread of infectious pathogens.

Chapter II Principles

Article 4 [Specialities] Cell products have the following special characteristics:

(I) [Safety of donor materials] Donor materials come from the human body and may contain infectious pathogens;

(II) [Production process characteristics] The quality of donor materials is affected by factors such as their source, type, and characteristics, and is different. Affected by this, the product production process may need to be adjusted as necessary according to the quality differences of donor materials and within the scope of product registration approval;

(III) [Production batch characteristics] Due to the limitations of the source and scope of use of donor materials, product production batches are usually small, the production organization model is relatively flexible, and production is more closely integrated with clinical needs;

(IV) [The influence of temperature] Temperature has a more significant impact on the quality of donor materials and products;

(V) [Preventing contamination and cross-contamination] In the production process after the collection of donor materials, since the products are living cells, they are easily contaminated or cross-contaminated by microorganisms, and contaminants are not easy to remove;

(VI) [Preventing confusion and errors] Autologous cell products or products produced with allogeneic donor materials that need to be matched with patients, once confusion occurs, resulting in a mismatch between donor materials or cells and patients, may have serious life-threatening consequences for patients.

Article 5 [Special Control] In view of the above-mentioned special characteristics of cell products, enterprises shall take special control measures for the whole process of donor material collection and product production, including at least:

(I) Conduct risk assessment on the product and its whole process from the receipt of donor materials to the storage and transportation of finished products, and formulate corresponding risk control strategies to ensure the safety, effectiveness and quality control of the product;

(II) Establish a biosafety management system and records, have facilities and equipment to ensure biosafety, prevent and control biosafety risks in the product production process, and prevent the introduction and spread of pathogens;

(III) Monitor the temperature and operating time limit of the product or production environment during the transportation and receipt of donor materials and the production, storage and transportation of products to ensure that the corresponding operations are completed within the specified temperature and time limit;

(IV) Special attention should be paid to preventing microbial contamination or cross-contamination during the whole process of product production, including the cross-contamination that may be caused to the product by the production process of the vector, and the cross-contamination that may exist in the production process of different vectors;

(V) From the collection of donor materials to the use of patients, the product should be correctly labeled and traceable to prevent confusion and errors.

Chapter III Personnel

Article 6 [Qualification of Key Personnel] The person in charge of production management, the person in charge of quality management and the person authorized by quality shall have the corresponding professional knowledge (microbiology, biology, immunology, biochemistry, biological products, etc.) and be able to perform their duties in production and quality management.

Article 7 [Personnel Safety Protection Training] Personnel engaged in cell product production, quality assurance, quality control and other related personnel (including cleaning and maintenance personnel) shall undergo biosafety protection training, especially relevant knowledge training on preventing the transmission of infectious pathogens through donor materials. All training content shall comply with relevant national regulations on biosafety.

Article 8 [Restrictions on Personnel Activities] During production, if effective decontamination measures are not taken as required, personnel engaged in vector production shall not enter the production area of cell products, and personnel who come into contact with donor materials containing infectious pathogens shall not enter other production areas.

Chapter IV Plants, Facilities and Equipment

Article 9 [Plant Zoning Design] Genetically modified viral vectors directly used in cell product production should be produced in separate production areas from cell products and other vectors or biological materials, and equipped with independent air conditioning purification systems.

Article 10 [Requirements for production plants for donor materials containing infectious pathogens] When using donor materials containing infectious pathogens to produce cell products, the production operation shall be carried out in an independent dedicated production area, and an independent air conditioning purification system shall be used to maintain a relatively negative pressure in the production area where the product is exposed to the environment.

Article 11 [Closed system] It is advisable to use a closed system or equipment for the production operation of cell products; the cleanliness level of the environment where the closed system or equipment is placed can be appropriately reduced.

Article 12 [Cleanliness level of the production operation environment] The cleanliness level of the production operation environment of cell products, genetically modified vectors or other starting biological materials directly used for cell product production can be selected according to the examples in the table.

Note: The production operation examples in the table, except for Class D, refer to operations under non-closed systems.

Article 13 [Isolated Storage] Donor materials and corresponding cell products containing infectious pathogens shall be stored in a separate isolated area, separate from the storage areas of other donor materials and corresponding cell products that do not contain infectious pathogens, and use independent storage equipment. Both the isolated area and the storage equipment shall be clearly marked.

Article 14 [Testing Laboratory] Donor screening, donor material and cell product testing laboratories used for infectious pathogen marker inspection, or testing samples containing infectious pathogens shall comply with the relevant national regulations on laboratory biosafety, and shall have in-situ inactivation or disinfection equipment when necessary.

Specific news link: The General Department of the National Medical Products Administration publicly solicits opinions on the "Good Manufacturing Practice for Pharmaceuticals - Appendix to Cell Therapy Products (Draft for Comments)"