With the continuous improvement of China's drug regulatory laws and regulations, Life-cycle regulatory management has become a key means and an inevitable development trend to ensure the safety of public drug use. The management of post-approval changes to biological products is gradually shifting towards the risk-based model from the item-based model.In recent years, there has been a significant increase in supplementary applications for manufacturing site changes of marketed therapeutic recombinant protein drugs. However, the risks associated with manufacturing site changes vary under different circumstances. Therefore, the research that needs to be carried out is also different. This paper provides an in-depth discussion on three key aspects: risk assessment and grading, general requirements and special considerations for pharmaceutical research, and common application issues. It outlines general requirements for manufacturing site change, aiming to offer valuable insights for industry needs. Through the collaborative efforts between regulatory authorities and the industry, patient rights and interests can be effectively protected, and high-quality drugs can be made available to the public.

In recent years, the rapid development of stem cell transforming technology and regeneration pose great re?search value. With maturation of transformation induction, other cell lineages were shown to be able to transform into neu?rons. In addition, astrocytes are widely distributed in the gray and white matter of the central nervous system, whose exces?sive proliferation contribute to glial fibrillary scar formation, which is the key obstacle in recovery of neurological function. Therefore, the study of transforming astrocytes into neurons draw attention from many scientists. Astrocytes transformation not only prevent the formation of glial scar, but also generate new neurons. This article summarized relevant studies that re?port function of astrocytes and its transformation into neurons.

Objective To investigate the effect of the overexpression of NeuroD1 on mediating transdifferentiation of spinal reactive astrocytes into neurons. Methods Spinal cord astrocytes were cultured from the SD rat, and reactive astrocytes were prepared by scratches treatment. Cells were divided into blank groups (NV group), control virus group (GFP group) and NeuroD1 virus group (NeuroD1 group). At 7 d after scratches treatment, GFP and NeuroD1 groups were infected with retroviruses carrying the GFP gene and and GFP gene plus NeuroD1 gene, respectively,whereas NV group was not infected with the virus. Twenty-four hours late, the culture medium were replaced by neuron conditioned medi?um. Cell morphology was examined at 1, 2, 3, 5, 7 and 14 d. DCX positive and NeuN positive cells were detected at 7 d and 14 d after infection by using immunofluorescence staining method, respectively. Results After replacement with the neuron conditioned medium, the nucleus was obviously plump, the cytoplasm was thin and neurites was reduced and ex?tended. Compared with the NeuroD1 group, neurites of NV group and GFP group were shorter with many branches and the nucleus was smaller. At 7 d after infection, cell morphology of NV group and GFP group gradually recovered, but cell morphology of NeuroD1 group did not. Compared with NV group and GFP group, NeuroD1 group had more DCX(9.84 ± 2.06%)and NeuN(8.25±2.78%)positive cells [F values 40.107 for DCX and 21.73 for NeuN (P<0.05)]. Conclusion The overexpression of NeuroD1 can mediate the transdifferentiation of spinal reactive astrocytes into neurons.