Human retinal pigment epithelial cells

Abstract 'Human retinal pigment epithelial cells' is the first set of guidelines on human retinal pigment epithelial cells in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies technical requirements, test methods, inspection rules, instructions for usage, labelling requirements, packaging requirements, storage requirements and transportation requirements and waste disposal requirements for human retinal pigment epithelial cells, which is applicable to quality control during the process of manufacturing and testing of human retinal pigment epithelial cells. It was originally released by the Chinese Society for Cell Biology on 9 January 2021. We hope that publication of these guidelines will promote institutional establishment, acceptance and execution of proper protocols and accelerate the international standardization of human retinal pigment epithelial cells for applications.


| SCOPE
This document specifies the technical requirements for human retinal pigment epithelial cells, and the requirements for the test methods, instructions for use, labelling, packaging, storage, transportation and waste disposal.
This standard is applicable for the production and testing of human retinal pigment epithelial cells.
Note: Human retinal pigment epithelial cells include primary sources and stem cell differentiation sources.

| NORMATIVE REFEREN CE S
The following content constitute indispensable articles of this standard through normative reference. For dated references, only the edition cited applies. For undated references, only the latest edition (including all amendments) applies.

| TERMS AND DEFINITI ON S
The following terms and definitions apply to this document.

| Human retinal pigment epithelial cell
The hexagonal monolayer epithelial cells containing pigment granules, which can be acquired by primary isolation from human retina, differentiation from stem cell and trans-differentiation from other somatic cells.

| ABBRE VIATIONS
The following abbreviations apply to this document. packaging requirements, storage requirements and transportation requirements and waste disposal requirements for human retinal pigment epithelial cells, which is applicable to quality control during the process of manufacturing and testing of human retinal pigment epithelial cells. It was originally released by the Chinese Society for Cell Biology on 9 January 2021. We hope that publication of these guidelines will promote institutional establishment, acceptance and execution of proper protocols and accelerate the international standardization of human retinal pigment epithelial cells for applications. and cells. The source material shall be accompanied with detailed documentation on the acquisition methods and donor information, including but not limited to the donor's general information, past medical history and family history. The information of donor's blood type (e.g., ABO, Rh) and human leucocyte antigen (HLA) alleles should be documented as necessary.
5.1.4. The origin of cells shall be traceable by referring to the relevant informed consent and/or their genome and functional data. 5.1.5. Ancillary materials such as culture medium and growth factors shall meet the corresponding quality control requirements. The ancillary materials can be inspected and laboratory tested if necessary. 5.1.6. When using animal serum, they shall be free of contamination by viruses of animal origin. Serum from animals in geographical regions with prion epidemics (e.g., bovine spongiform encephalopathy) shall be prohibited.
5.1.7. If human blood components are used in the culture medium, including but not limited to albumin, transferrin and various cytokines, the source, batch number and quality verification reports shall be provided. State-approved products shall be used as much as possible.
5.1.8. The donors shall be screened for HIV, HBV, HCV, HTLV, EBV, HCMV and TP, and the results shall be documented.

| Cell morphology
Pigment can be seen in the cells. Under the condition of monolayer adherent growth, the cells are in close contact and polygonal.

| Chromosome karyotype
The normal karyotype shall be 46, XY or 46, XX.

| Cell marker protein
The expression of ZO-1 shall be ≥ 70% of the cell population. The expression of at least any three of the cell markers RPE 65, OTX2, MITF and BEST1 shall be ≥ 70% of the cell population.

| Secretory function
Shall have the capacity of secreting PEDF and VEGF.

| Cell STR identification
The STR signature of hRPEs shall be consistent with that of donor cells.

| Cell morphology
Under the condition of two-dimensional adherent culture in vitro, the cells shall be cultured for at least 10 days and observed by inverted microscope.

| Chromosome karyotype
The method in the Pharmacopoeia of the People's Republic of China shall be followed.

| Cell survival rate
The method in Appendix A shall be followed.

| Cell markers
The method in Appendix B shall be followed.

| Secretory function
The method in Appendix C shall be followed. 6.6 | Microorganisms 6.6.1 | Fungi 6.6.1. The method in Pharmacopoeia of the People's Republic of China shall be followed. 6.6.2 | Bacteria 6.6.2. The method in Pharmacopoeia of the People's Republic of China shall be followed.

| Mycoplasma
The method in Pharmacopoeia of the People's Republic of China shall be followed.

| HIV
The method in WS 293 shall be followed.

| HBV
The method in the National Guide to Clinical Laboratory Procedures shall be followed. 6.6.6 | HCV According to WS 213 nucleic acid method. 6.6.7 | HTLV The method in the National Guide to Clinical Laboratory Procedures shall be followed.

| EBV
The method in the National Guide to Clinical Laboratory Procedures shall be followed. 6.6.9 | HCMV The method in the National Guide to Clinical Laboratory Procedures shall be followed. 6.6.10 | TP The method in WS 293 shall be followed.

| Sampling method
7.1.1. Cells produced from the same production cycle, same production line, same source, same passage and same method are considered to be the same batch. 7.1.2. Three smallest units of packaging shall be randomly sampled from the same batch.

| Quality inspection and release
7.2.1. Each batch of products shall be subject to the qualify inspection before release, and inspection reports shall be attached. 7.2.2. The quality inspection items shall include all the attributes specified in 5.2.

| Review inspection
Review inspection shall be performed by professional cytological testing institutions/laboratories as necessary.

| Decision rules
7.4.1. Products that pass all requirements in 5.2 for the quality inspection for release are considered to be qualified. Products that fail to pass one or more requirements in 5.2 for the quality inspection for release are considered to be unqualified. 7.4.2. Products that pass all requirements in 5.2 for the quality review inspection are considered to be qualified. Products that fail to pass one or more requirements in 5.2 for the review inspection are considered to be unqualified.

| IN S TRUC TI ON S FOR USAG E
The instructions for usage shall include but not limited to:

| WA S TE D IS P OSAL
11.1. The waste generated during the production and testing of human retinal pigment epithelial cells shall be in accordance with the waste cell management documents, strict implementation of management standards and detailed records.