Single-cell sequencing advances the research of molecular biology and cell biology to the single cell level by integrating the latest technologies such as single-cell dissociation, microfluidic, microfluidics system, high-throughput sequencing, and bioinformatics. It is a milestone technology in the history of biotechnology. Single-cell sequencing technology provides a new dimension for the study of basic biomedical problems such as ontogeny, cell differentiation, cell heterogeneity in tissues, and the etiology and development of diseases, and has been widely used. In this review, we briefly introduced the development of single cell sequencing technology and assocatied bioinformatics methods, and reviewed its application in the process of drug development, such as study on mechanism of disease, target discovery, drug discovery and optimization, mechanism of action and clinical trial design.

The manufacturing process of fermented new drugs is complicated, and the quality control is difficult. Referring to the relevant technical guidances of new drug chemistry, manufacturing, and control research, centering on the quality control characteristics of fermented new drugs, this article discusses the general considerations on the manufacturing process, elucidation of structure, specification research, to provide a reference for the research of fermented new drugs.

Continuous manufacturing is one of the development directions of the production process of recombinant biotechnology products in the future. The promulgation of important technical documents such as ICH Q13 also provides guidance for its application practice. However, in the field of viral safety control, there are great differences in control concepts and measures between continuous manufacturing and previous batch manufacturing mode. Starting with the process characteristics of continuous manufacturing, this paper makes a preliminary discussion on three aspects, which are the control of raw materials, in-process test, and virus removal/inactivation process validation. At the same time, as the cases of continuous manufacturing of recombinant biotechnology products are still limited, more comprehensive and meticulous control strategies and measures still need further accumulated and improved based on R&D and production experience. It is suggested that the applicants of this kind of products should fully communicate with the regulatory authorities before the application, so as to ensure the safety of the subjects or patients through scientific and rigorous trial design.

As a continuous cell culture technology, perfusion fermentation is more beneficial to cost control than traditional batch fermentation and can be flexibly arranged according to the supply change. In this paper, the characteristics and advantages of perfusion fermentation are clarified by comparing the batch fermentation with perfusion fermentation. In combination with the guidelines currently being drafted by the International Council on Harmonization, the considerations for pharmaceutical evaluation of cell passage stability study, batch and scale definition, process control, viral safety, and process verification of perfusion fermentation are summarized in this paper.

Complex injections are usually a kind of modified new drugs with new dosage forms, formulations and manufacture processes. It is an effective method to reduce inherent deficiencies of active ingredients with advanced techniques. Complex injections can reduce side effects of drug substances, improve drug efficacy, promote patients' compliance and so on. In the increasingly competitive generic drug market, they have obvious clinical advantages and market competitiveness. However, complex injections usually own complicated formulations and processes. Based on guidances and policies at home and abroad, in this paper, we briefly discussed the CMC requirements for complex generic injections according to the characteristics of different complex injections.

"Risk Assessment and Mitigation Strategies" (REMS) are procedures used by the U.S. Food and Drug Administration (FDA) to manage known or potentially serious risks associated with a drug to ensure that the benefits of the drug outweigh its risks. CAR-T cell therapy has brought new hope and new options for cancer patients due to its excellent efficacy. However, due to the characteristics of its treatment principle, almost all CAR-T cell therapy may lead to some adverse reactions. Cytokine release syndrome (CRS) and neurologic toxicities (NT) are the most common. This paper intends to analyze the post-marketing risk management strategies of CAR-T drugs in the United States by exploring the content of REMS in the risk management strategies of CAR-T drugs, and takes Kymriah, a CAR-T product currently on the market in the United States, as an example to analyze the specific implementation of the strategies. The purpose of this paper is to provide reference for the authorities to develop related policies of CAR-T drug listing risk management in China.

Clinical study for medicine products is a time-consuming and high-cost project. As a great tool of optimizing trial design, simulation technology plays an important role in different phases and different indications of clinical trials. At present, different regulatory agencies have established corresponding technical requirements for simulation technology. This paper summarized the development of the guidelines of NMPA, FDA, EMA, and ICH to elaborate the regulatory status of simulation technology. Without additional clinical trial data, one pharmaceutical company successfully expanded the indications of adalimumab in adults for hidradenitis suppurativa to adolescent by virtue of only model simulation results. This article analyzed this case in detail to illustrate the importance of simulation technology. Finally, this paper discussed the advantages and disadvantages of simulation technology, as well as the considerations in practical application.

Bcr-Abl inhibitors are targeted drugs for the treatment of chronic myeloid leukemia (CML). Due to the high selectivity with few side effects, some of them have become the first-line drugs in the treatment of CML. Therefore, Bcr-Abl inhibitors have become the hotspot of anti-CML drug research. Based on the patent publication records of Bcr-Abl inhibitors, this article analyzes the research and development trends of Bcr-Abl inhibitors from the publication time and regional distribution, compares and analyzes the research progress through technical topics, and finally selects an enterprise to analyze its subsequent patent application for drug research and development in China and abroad, in order to provide relevant reference for the research and development of Bcr-Abl inhibitors.

Objective: To compare the effects of different extraction methods on polysaccharides from Polygoni Multiflori Radix, and to explore the differences of polysaccharides from Polygoni Multiflori Radix and Polygoni Multiflori Radix Praeparata using hot water extraction. Methods: Polysaccharides from Polygoni Multiflori Radix were extracted by hot water extraction, ultrasonic extraction and microwave extraction, respectively. The yield, total sugar content, protein content, weight-average molecular weight (M_w), monosaccharide composition and DPPH free radical scavenging ability of polysaccharides were studied and compared. Results:The results showed that the yield of polysaccharides from Polygoni Multiflori Radix by different extraction methods was as follows: microwave extraction (M-PMP) > hot water extraction (H-PMP) > ultrasonic extraction (U-PMP). The protein content of U-PMP was the highest, and the M_w was obviously different from other polysaccharides. The results of monosaccharide composition showed that the monosaccharide composition of polysaccharide from Polygoni Multiflori Radix by different extraction methods was the same, which is mainly composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose and arabinose, with different molar ratio of monosaccharides. Conclusion:There are some differences in the polysaccharide components extracted by three methods, and the yield obtained from different extraction methods varied significantly, with the highest yield of M-PMP. Some differences were found in polysaccharides from raw and prepared Polygoni Multiflori Radix and Polygoni Multiflori Radix Praeparata.

Rhein is a kind of emodin-type hydroxy-anthraquinone, which mainly exists in traditional Chinese medicines like rhubarb. Rhein is well acknowledged for its pharmacological activities, such as anti-cancer, anti-inflammatory, anti-bacterial and anti-Alzheimer's disease; however, its clinical application is limited due to its poor water solubility and low bioavailability. In order to overcome these shortcomings, a large number of more bioactive Rhein derivatives were designed and synthesized by structural modification of Rhein. In this paper, the structural modification and pharmacological activity of rhein are reviewed, providing reference for future development of rhein derivatives.