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.

The guidance on CMC study of in vivo gene therapy products was issued by the Center for Drug Evaluation, NMPA, on May 26, 2022, to encourage and promote the development of in vivo gene therapy products. This paper gives a detailed interpretation of the main contents and some important issues of the guidance and provides a reference for the market authorization application, combined with the drafting process of the guidance, so that the industry can better understand the technical requirements of the guidance during the development of in vivo gene therapy products.

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.

In order to encourage clinical value-oriented drug innovation, the current "Drug Registration Regulation" proposes four expedited regulatory approval procedures. For innovative drugs with early clinical trial data that can likely predict the efficacy and clinical benefit of the drugs, the marketing authorization might be granted before the completion of the confirmatory clinical trial through the conditional approval procedure, with all data comprehensively reviewed. By implementing the procedure, patients with serious diseases or conditions can expect more opportunities to prolong their lives or improve their quality of life. Since conditional approval procedures can shorten the time for pre-market clinical research and development, its supporting policies and criteria have attracted much attention. This paper takes the innovative anti-tumor drugs as the starting point, systematically sorts out the policy requirements of conditional approval in China and the criteria that have been formed in the review process, and tries to analyze the problems encountered in the implementation of conditional approval and put forward solutions.

"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.

For post-approval CMC Changes, ICH Q12 proposed management tools such as categorization of post-approval CMC changes, ECs, PACMP, and PLCM documents. The United States, the European Union and China have different approaches in implementing these management tools. It is of great significance to learn from and refer to the implementation experience of the United States and the European Union for optimizing China's post-approval CMC change management. We hope to change the supervision department's concept of post-approval CMC change management, manage changes by category, and optimize change management tools.

Objective: To optimize the parameters in separation and purification processes of Yixintai total saponins, by using failure mode and effects analysis (FMEA) combined with Box-Behnken response surface design. Methods: The total saponins of Yixintai Compound were purified with macroporous resin (MAR), and the key process parameters of the purification process were screened by FMEA. Taking the recovery rate and mass fraction of saponins as evaluation indicators, the Box-Behnken design was used to optimize the MAR purification process of Yixintai total saponins. The optimal parameters were finally obtained in separation and purification processes of Yixintai total saponins. Results: FMEA determined four influencing factors, including the mass concentration of the sample solution, eluent volume fraction, the adsorption flow rate and the volume of the eluent as the key factors for the separation and purification of total saponins. The P values of the models established by Box-Behnken design were all below 0.05, indicating that the models had good predictive abilities. The obtained best parameters was are as follows: the mass concentration of the sample solution is 0.80 mg·mL^-1, the ethanol volume fraction is 90.0%, the adsorption flow rate is 1.7 BV·h^-1, and the eluent volume is 1.6 BV. Conclusion: The separation and purification method obtained by failure mode analysis combined with Box-Behnken optimization was stable and reliable, with high recovery rate and purity of saponins. This method is suitable for purifying Yixintai total saponins.

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.

Objective: To establish a method for controlling polymer impurities in ceftizoxime sodium for injection. Methods: Ceftizoxime sodium was dissolved in phosphate buffer solution (pH 7.0) to prepare degradation solution. High performance size exclusion chromatography (HPSEC) and column switching-LC/MSn (CS-LC/MSn) were applied to separate and deduce the poor retention impurities in the degradation solution. The specificity of developed HPSEC method was evaluated. A RP-HPLC method for polymer analysis was established with a Phenomenex Gemini C₁₈ column, using phosphate buffer solution (pH 7.0)-acetonitrile as mobile phase under a gradient elution program. The specificity of RP-HPLC method was assessed by two-dimensional chromatography (2D-HPLC) and CS-LC/MSn, and LLOD and LLOQ were also tested. Results: ceftizoxime dimer and the dimer's isomer were deduced in the degradation solution as well as 6 small molecular impurities. Polymer impurities were liable to co-elute with small molecular impurities by HPSEC method, which made a poor quantification accuracy and specificity. Ceftizoxime dimer and the dimer's isomer were detected by RP-HPLC with a sufficient specificity. Conclusion: HPSEC method was not suitable for the quality control of polymer impurities in ceftizoxime sodium for injection, while the RP-HPLC method was specific, which can be applied for polymer impurities. Ceftizoxime degradation solution can be used to identify polymer peaks as the systematic suitability testing solution.