Objective: To identify the advantages and disadvantages of the regulations related to the production of traditional Chinese medicine (TCM) by conducting a benchmarking study on the annex of PIC/S GMP for herbal medicine production, and to provide a theoretical basis for China's smooth accession to the Pharmaceutical Inspection Co-operation Scheme (PIC/S). Methods: A comprehensive comparison was conducted among Chinese GMP decoction pieces, Chinese medicinal preparations annex, relevant regulations and the PIC/S GMP annex for Herbal Medicines production. An analysis and discussion were carried out on certain advantages and differences. Results: The requirements of China's GMP appendices for TCM decoction pieces and preparations, as well as related regulations, were essentially consistent with those of the PIC/S GMP annex for Herbal Medicines in all aspects. Moreover, China's TCM regulatory regulations were more comprehensive and specific in terms of plant and facilities and equipment, personnel, confirmation and verification, production management, and quality control and other requirements compared to the PIC/S GMP Herbal Medicines. Conclusion: China's relevant laws and regulations related to TCM production have a solid foundation and already meet the requirements of the PIC/S GMP annex for Herbal Medicines. Moving forward, it is essential to maintain confidence, clarify the direction, and further refine the regulatory requirements for TCM production in China.

Objective: To explore the mechanism of action of Lianchen Decoction in treating phlegm-dampness obesity based on network pharmacology and molecular docking technology. Methods: TCMSP was used to obtain the active ingredients and target of Lianchen Decoction. Disease targets were obtained through GeneCards, TTD, and OMIM. The related targets of phlegm-dampness type were obtained by SoFDA. The network was constructed using Cytoscape3.10.1 software to screen key active ingredients and core targets through topological analysis. GO function enrichment and KEGG signaling pathway enrichment analysis were performed on potential targets using Weisheng platform. AutoDockVina software was used for molecular docking of components and targets. Results: 148 targets, 9958 targets of disease and 896 targets of phlegm-dampness were obtained. The targets were intersected and 106 potential targets were obtained. The network topology analysis showed that glycerol, citromitin and mupingaristolamide were the key active components. PPI network analysis screened out MC4R, PPARG, FTO, GHRL and other active targets. GO functional enrichment analysis showed that there were three parts: biological process, cell components and molecular function. KEGG pathway enrichment analysis showed that the target was mainly concentrated in insulin resistance related pathways. Conclusion: Lianchen Decoction may act on MC4R, PPARG, FTO, GHRL and other core targets to regulate insulin resistance pathway and insulin signaling pathway through the action of key active ingredients such as glycerol, citromitin, mupingaristolamide, and play a role in the treatment of phlegm and dampness type obesity.

Objective: To further improve the quality and efficiency of communication on innovative chemical drugs, and to increase support for innovative drug research and development, as well as strengthen technical guidance and services for applicants. Methods: Based on the relevant technical guidelines and review practices of pharmaceutical at different application stages of innovative drugs for registration, this paper puts forward suggestions on the pharmaceutical problems existing in relevant communication. Results and Conclusion: Solutions and focus points for the common problems in the communication of innovative chemical drug at different application stages for registration are proposed, hoping to provide references for drug registration applicants, improve the quality and efficiency of communication, and better serve drug innovation and development.

Objective: To provide references for the selection mechanism and procedure of reference medicinal product for consistency evaluation in China and to provide ideas for generic enterprises to select the reference medicinal product. Methods: The current reference medicinal product in ANDA draft guidance by US food and drug administration (FDA), as well as the relevant requirements of reference medical product in European Union (EU), Japan and WHO were introduced in details. Some suggestions to improve the selection procedure of reference medicinal product were put forward according to the present situation of consistency evaluation of generic drugs in China. Results and Conclusion: US specifed the ideas and practical operation procedures for the selection of reference medicinal product for generic drugs, which provided new ideas to select the reference medicinal product in China. China is in the critical period of the selection reference medicinal product for generic drugs consistency evaluation. It is necessary to formulate a comprehensive and perfect selection system and mechanism of reference medicinal product, which can help to standardize the selection procedure of reference medicinal product, to speed up the process of consistency evaluation, and to enhance the scientificity and completeness of the selection of reference medicinal product for generic drugs consistency evaluation in China.

Objective: To introduce the problems of hygroscopic chemical reference substances in drug regulatory application and give suggestions, in order to provide reference for better application of national drug reference substances in drug regulation. Methods: Regulations related to pharmaceutical reference substances were expounded, and the problems encountered in the use were analyzed and the hygroscopic chemical reference substances by dynamic vapor absorption analysis (DVS) were studied. Suggestions from the aspects of standard implementation, instructions, packaging and storage, weighing and moisture determination were provided. Results and Conclusion: Chemical reference substances with hygroscopic properties are a relatively special type of reference standard. Due to their hygroscopic properties affecting the stability of measurement values, they has posed several problems and challenges to drug regulation. Through the achievements of research on hygroscopicity, the improvement of reference standard instructions, and the summary of practical work experience, all parties are working together to solve the problems and better improve the application of national reference substances, in order to ensure the effectiveness of drug regulation and the safety of drug.

Objective: To summarize and analyze the current situation of drug import filing work, explore the trend of fine-tuning the current drug import filing system in China, and provide reference for future policy formulation and optimization reform. Methods: By using literature review, data statistics, and comprehensive analysis methods, the problems existing in drug import filing were sorted out, and the main causes management status of various problems were found out. The policy trend in recent years regarding the announcement of relevant documents for drug import filing in China was studied. Results: Solutions were proposed for the existing problems, and the implementation of the new method effectively improved the current situation of drug import filing. Conclusion: This study helps to enhance understanding of the relevant laws and policies on drug import registration, and facilitates their rational application in practical work. It is suggested to flexibly adjust the review rules for the implementation of drug import filing in accordance with international development trends, in order to ensure compliance declaration by enterprises and improve the efficiency of imported drug clearance.

Objective: To analyze the current market quality problems on the basis of investigation and inspection, to study the authenticity identification methods of the traditional Chinese medicine (TCM) bletillae rhizoma and to provide suggestions for drug supervision. Methods: Literature reviews, investigation into the producing areas and markets, and the inspection data were combined to analyze the quality problems of bletillae rhizoma and their causes, and the solutions were put forward. Results: The main quality problems of bletillae rhizoma was the adulteration of the same genus or similar species. The percentage of unqualified bletillae rhizoma was 9% according to the national sampling inspection for the TCM crude drugs and prepared slices. It was difficult for the single detection method to authenticate the bletillae rhizoma due to the complex varieties of the fakes. However, the combined characteristic technologies can distinguish bletillae rhizoma from the fakes efficiently. Conclusion: Although there are a wide variety of counterfeit bletillae rhizoma, the quality problems are still acceptable. In order to improve the quality of the TCM crude drugs and prepared slices of bletillae rhizoma, we should strengthen the source management starting from standardized production.

Objective: To provide suggestions and references for the pharmaceutical research of genome editing systems in advanced therapy medicinal products. Methods: Based on the pharmaceutical research, combined with the requirements of relevant regulation and guidance domestically and abroad, this article focused on the upstream design, production and quality research, use and risk management of genome editing systems. Results and Conclusion: In recent years, genome editing systems represented by CRISPR/Cas9 have risen rapidly as scientific research hotspot, and have been widely used in many fields such as medicine, agriculture, biotechnology and so on. In the field of therapeutics, genome editing systems can not only be used as active pharmaceutical ingredients or drug substances in vivo, but also play a therapeutic role after editing cells in vitro and returning to the human body. So it is an important concern in the evaluation of advanced therapy medicinal products. This article raised the current considerations for pharmaceutical research, hoping to promote the clinical transformation and application of genome editing products.

Objective: This article aims to study the analysis methods of visible particles test in the major Pharmacopeias worldwide and to provide some suggestions and ideas for the upgrade of the visible particles test in the Chinese Pharmacopeia. Methods: Through reviewing the major Pharmacopeias worldwide, the definition of visible particles, the manual visual inspection, and the judgment standards of visible particles were analyzed and compared, and the similarities and diff erences of the major Pharmacopeias worldwide were summarized. Results: The Pharmacopeias worldwide were differences in the definition and judgment standard of visible particles, and there were diff erences in the requirements for detecting personnel, light sources, light intensity, inspection quantity, and specific operation methods of manual visual inspection. Diff erent Pharmacopeias showed certain strengths and weaknesses, and the detection parameters were both complementary and constrained. Conclusion: It is suggested that the Chinese Pharmacopoeia should combine the advantages and disadvantages of major Pharmacopeias worldwide, meanwhile, based on the current situation of Chinese enterprises, to further improve the content of the visible particles test and ensure the quality of drugs and the safety of people's medication.

Objective: To explore the trend of traditional Chinese medicine (TCM) research and development, as well as the current status of registration review and approval since the implementation of the new version of Drug Registration Regulations published in 2020, so as to provide references for the strategic layout of enterprises on the TCM product research and development. Methods: Registration application and review approval status of all the TCM preparations submitted in 2021-2024 were systematically analyzed from multiple perspectives such as quantity, type, registration classification, treatment field, dosage form and application stage. Results: The number of registration applications for TCM preparations had been increasing year by year, with the main type being new traditional Chinese medicine. The registration classification involved innovative traditional Chinese medicine, improved new drugs, ancient classic prescriptions, drugs with the same name and prescriptions, including the situation like applications for marketing of innovative medicine of natural medicine (Type 1.1). The treatment field was focused on the advantageous area of TCM, and the dosage form is mainly oral. Conclusion: Enterprises on the TCM product resarch and development should strengthen the exploration of the advantages of famous TCM prescriptions, attach importance to the secondary development of existing varieties, and comprehensively consider the strategic layout combined with the variety pipeline and their own advantages, and seize the good opportunity of high-speed and high-quality development of TCM.

Objective: International ADR monitoring has developed for many years, and a mature drug reporting quality assessment method has been formed, but there has never been a scientific, systematic, and quantitative evaluation method for the quality of cosmetics adverse reaction reports, both domestically and internationally. In order to improve the quality of cosmetic adverse reaction report, strengthen the analysis evaluation, the basis of risk early warning, a standard method for assessing the quality of adverse reaction reports for cosmetics was established for the first time by drawing on international experience in monitoring adverse drug reactions. Methods: Based on the international quality assessment method of ADR reporting, this study established and operated the "manual sampling score addition" and "computer case-by-case multiplication weight reduction method", which enabled the method of cosmetics report quality assessment in China to achieve a leap from scratch and from existence to excellence. Results: After the application of the report quality evaluation method, the status quo and level of the report quality across the country were mastered by scoring, and the problems and deficiencies of the monitoring work were found out, and then targeted measures such as formulating technical guidelines and providing training guidance were taken to improve the quality of the report. Conclusion: Adverse reaction report is the foundation of adverse reaction monitoring work. Through quantitatively evaluating report quality, identifying the problems and deficiencies, continuously improving the quality of report, a true, complete and accurate information basis is provided for the subsequent analysis evaluation and risk early warning, which provide strong technical support for China's cosmetics regulation and public health safety.

Objective: To analyze the key focuses of sterile production environmental monitoring and common defects in inspection, with the aim of providing references for improving the environmental monitoring capacity of sterile drug production enterprises and providing inspection ideas for the GMP sterile inspection of the environment. Methods: The regulations and contents of sterile drug production environmental monitoring were summarized, and the common confusing aspects in environmental control and air conditioning purification system confirmation during sterile inspection were analyzed. The establishment and implementation of the full life cycle environmental monitoring procedure were proposed, and the typical defects of environmental monitoring from the perspective of GMP sterile inspection were summarized. Results: Environmental monitoring and environmental control, air conditioning purification system confirmation correspond to different regulatory requirements and have their own monitoring focus. From the perspective of inspection, typical defects of environmental monitoring include imperfect establishment of environmental monitoring procedures, inaccurate assessment of risk points, doubts about the authenticity of monitoring data, and failure to make effective use of monitoring data. The establishment and implementation of the environmental monitoring procedure based on the full life cycle concept is a key link in ensuring the quality of sterile drugs. Conclusion: In order to ensure the quality of sterile drugs,sterile drug production enterprises need to comprehensively evaluate the implementation of environmental monitoring and improve the relevant program content. Sterile drug production environment monitoring is a key focus of GMP sterile inspection. As drug regulatory agency, adhering to the full life cycle inspection approach in inspection is an important inspection technique for objectively evaluating the sterile drug production enterprises' sterile protection capacity.

Objective: To propose management strategies for sponsors, production sites, and their changes during the clinical research phase of new drugs in China, to provide reference for adapting to the new situation of drug research and development and improving China's drug regulatory policies. Methods: This study analyzed the current issues in the management of sponsors and production sites in the clinical research phase in China, drew on the management experience of foreign regulatory agencies, conducted comprehensive assessment and judgment based on risk principles, and proposed relevant management countermeasures and suggestions suitable for China's national conditions. Results and Conclusion: With the core of ensuring the safety of subjects and the goal of encouraging innovation and improving the accessibility and availability of public medication, this study proposes specific management suggestions on strengthening the responsibility of sponsors as the main body, strengthening the quality management of clinical trial drug preparation, the pilot situation of moderately relaxing the cross- border and cross-border changes of applicants/sponsors and clinical trial drug production sites.

Objective: To enable more relevant scholars to understand the development and record of the species of Hirudo (leeches) through a more clear historical context, and to use relevant Chinese names and nicknames more strictly in various scenarios in the future. Methods: By collecting domestic research literature related to three medicinal leeches included in pharmacopoeia from the early days of the founding of the People's Republic of China to the present day, as well as family and genus, combining with some earlier foreign records and the data of the present main shared database, the family and genus classification of several leeches, species merger and separation, and the corresponding Chinese names and Latin scientific names were sorted and analyzed. Results: Since the founding of the People's Republic of China, Hirudo has been included in the Pharmacopoeia of the People's Republic of China since 1963. With the in-depth research of leeches, the classification of leeches has been adjusted continuously. At present, the family and genus classification of leeches has gradually differentiated into two relatively independent usage habits, and there are some problems such as misuse of Chinese names. Conclusion: In order to ensure the accuracy of the source of species and prevent the ambiguity between research and use, it is suggested that pharmacopoeia should be supplemented by a variety of notes to confirm the original source. In addition, a new round of survey and sorting of leeches should be one of the important topics for leeches research.

Objective: To clarify the importance of quality control of pharmaceutical excipients by reviewing the incidents of ethylene glycol and diethylene glycol pollution and related regulatory requirements. Methods: Through sorting out the pollution incidents of ethylene glycol and diethylene glycol, as well as the relevant regulatory requirements issued by the United States and the World Health Organization, and combining with the warning letters of ethylene glycol and diethylene glycol pollution issued by the FDA, this paper puts forward some suggestions on the quality control of pharmaceutical excipients. Results and Conclusion: Glycerin and other pharmaceutical excipients by ethylene glycol, diethylene glycol pollution will produce more serious drug pollution events. The World Health Organization has repeatedly issued global medical alerts, FDA has also repeatedly warned against ethylene glycol, diethylene glycol pollution. The quality of pharmaceutical excipients and the quality of drugs is closely related. This paper analyzes the causes of ethylene glycol and diethylene glycol pollution, and puts forward suggestions on the quality system construction of excipient manufacturers, the control of excipient circulation links, the quality responsibility of drug manufacturers, the development and improvement of testing methods and equipment, and the coordination and cooperation of global regulatory authorities. It hopes to provide references for the industry to further improve the quality management and control of pharmaceutical excipients.

Objective: To establish a flow-through cell method for determining the release rate of bupivacaine multivesicular liposomes, and to explore the release mechanism of the multivesicular liposomes. Methods: Phosphate buffer solution (pH 7.0, containing 1% bovine serum albumin) was used as the release medium, with a volume of 100 mL. A dialysis tube with a molecular weight cut-off of 100 kDa was used in conjunction with a 22.6 mm tablet cell. The water bath temperature was maintained at 25 ℃. The flow rate was 16 mL · min^-1.The model-dependent methods were applied to fit the release curves of bupivacaine multivesicular liposomes produced by different manufacturing processes, to compare the similarity of the release curves, and to explore the release mechanism of the multivesicular liposomes. Results: The BiDoseResp mathematical model provided a good fit for the release curves of the three preparations produced by different manufacturing processes. Statistical analysis showed that the variances of the mean values for parameters A2 and h2 among the three preparations are homogeneous (P=0.391 > 0.05,P=0.151 > 0.05). The LSD test in multiple comparisons revealed that there was no significant difference in parameter A2 between batch 1 and the original product, while there were significant differences in parameter A2 between batch 2 and both the original product and batch 1 (P < 0.05). However, there were no significant differences in parameter h2 among the three preparations. The release of bupivacaine in liposomes involved both diffusion and erosion processes. As the drug was released from the liposomes, the liposomes themselves underwent structural rearrangement and dissolution. Conclusion: The flow-through cell method for determining the release rate of bupivacaine multivesicular liposomes is established, and its release curves can reflect the release characteristics of multivesicular liposomes. It can also preliminarily distinguish the release behavior of multivesicular liposomes produced by different manufacturing processes. This method provides a reference for the screening of generic drug quality control and consistency evaluation.

Objective: To provide reference for improving the regulatory system of drug clinical trials and change management during clinical trials by reviewing the corresponding regulatory requirements in China and investigating the current situation of the industry. Methods: Literature research on the regulatory requirements for clinical trials and their changes in China, as well as survey on the status quo of the industry, were conducted to provide reference suggestions for the subsequent improvement of the regulatory system of drug clinical trials and change management during clinical trials in China. Results and Conclusion: The reform of drug evaluation and approval in China has been continuously improved in recent years, and there are demands for “cross-border” and changes in sponsors and production sites along with the development of the industry. Considering the practical needs of innovative development and current regulations, under controllable risk conditions, China has a certain foundation to support the "cross-border" and "cross-border changes" of sponsors and clinical trial drug production sites.

Objective：To analyze the challenges and difficulties faced by drug regulatory inspections with the widespread application of informatization and intelligent equipment in the field of drug production, and to propose suggestions on how to improve the capabilities and level of production inspection. Methods The documents issued by drug regulatory agencies and international drug cooperation organizations in various countries were analyzed, and the current development status and existing problems of intelligent manufacturing of drugs in China were investigated. Results and Conclusion：China’s drug enterprises have begun to implement intelligent manufacturing in some scenarios, but have not yet formed a scale and integration. There are still many challenges in regulatory inspection, it is suggested to continuously exert efforts in issuing relevant inspection guidelines, improving the professional quality of inspectors, continuously exploring the application risk management, and developing regulatory science, etc., to jointly promote the intelligent manufacturing of drug production in China to the world.

With the rapid development of the global pharmaceutical industry and the advancement of precision medicine concepts, special dosage forms of drugs continue to emerge. These types of drugs are often embedded in special materials or contain special excipients, resulting in difficulties in sample dissolution, filtration, and removal of antibacterial properties, which is a challenge in establishing sterility testing methodology. This article focuses on three dimensions：key parameter optimization, the construction of specific methodology for special dosage forms (microsphere preparation, liposome preparation, protamine containing preparation, ophthalmic gel preparation and chitosan based preparation) and application of rapid microbial detection technology, in order to provide references for the establishment of sterile testing methods and quality control of special dosage forms of drugs.

Objective: To compare the regulatory policies of various provinces on the storage and transportation of drug third-party logistics, and to put forward feasible suggestions for strengthening the supervision of drug third-party logistics. Methods: By searching the websites of the National Medical Products Administration and provincial medical products administration, the regulatory policies on drug third-party logistics storage and transportation were obtained, the policies of diff erent provinces and the relevant provisions of the Good Supply Practic were compared and analyzed, and suggestions were put forward. Results: Through comparison, it was found that the policies of various provinces on storage and transportation mainly focused on the storage area, storage facilities and equipment, cold storage quantity and volume requirements, cold storage power supply guarantee, temperature and humidity monitoring system, storage management system, vehicle quantity and vehicle equipment, transportation vehicle management, special drug transportation, transportation management system and other aspects. However, there were some diff erences in the specifi c regulations of diff erent provinces. Moreover, the policy documents of most provinces still had problems: storage management policies were not unifi ed, storage areas were not clearly divided, storage facilities and equipment provisions were not specific, transport-related policies were not comprehensive, and provisions were not made to ensure the normal temperature environment during the transportation of normal temperature drugs. Conclusion: Drug regulatory authorities should strengthen the scientifi c supervision of drug third-party logistics, and establish a unifi ed third-party logistics management system. Drug third-party logistics enterprises should strengthen the construction of infrastructure and equipment, and strive to improve their own storage and transportation level. All relevant parties should make joint eff orts to promote the healthy and orderly development of the pharmaceutical third-party logistics industry.

Objective: To provide constructive suggestions for the radiation safety management of radioactive drug testing laboratories in drug inspection institutions. Methods: A brief analysis was conducted on the demand for radioactive drugs in the market and the current development status of inspection laboratories. The relevant concepts, classifications, and regulations of radiation safety management were outlined, and the requirements for the construction, licensing, retirement, and daily radiation safety management of radioactive laboratories were summarized. The common causes of radiation accidents in recent years were statistically analyzed, and the risks of radiation safety management in radioactive drug inspection laboratories were discussed. Targeted solutions were proposed. Results and Conclusion: The radioactive drug testing laboratory should aim at the forefront of international construction, strictly implement the "three simultaneities" of radiation project construction, continuously improve the radiation safety management system, adhere to strict education, training and assessment, equip with high standard facilities and equipment, continuously consolidate the foundation of radiation safety management, and promote the rapid development of new quality and safety productivity in radioactive drug inspection.

Objective: In order to provide suggestions for Chinese medicine manufacturers to carry out research on sterilization of traditional Chinese medicine, and to provide reference for the implementation of relevant supervision by the pharmaceutical supervision department. Methods: The regulatory requirements of traditional Chinese medicine sterilization and the conventional sterilization process of traditional Chinese medicine were sorted out, and typical problems were summarized and analyzed based on the cases of traditional Chinese medicine review and inspection. Results: There were some typical problems in the research of sterilization process of traditional Chinese medicine, such as unreasonable selection of sterilization conditions, insufficient research verification, improper research management and insufficient process control. Conclusion: It is suggested that enterprises should strengthen material management, strengthen production process control, determine the sterilization method of traditional Chinese medicine based on drug characteristics, and do a good job in change research and management to ensure the rationality and compliance of changes.

Objective: To study the regulatory requirements and implementation of the change management during the clinical research of drugs in Japan, and compare it with the current construction and implementation status of relevant regulatory regulations in China, in order to provide reference for improving the regulatory system of the change management of sponsors and production sites during the clinical research of drugs in China. Methods: A systematic review and study of regulatory regulations on the change of sponsors and production sites during the clinical research in Japan was conducted. Suggestions were provided based on the current situation of change management during the clinical research in China. Results and Conclusion: In Japan, the clinical trial sponsors and clinical trial drug production sites are allowed to apply for registration and change of clinical trials both domestically and internationally. The regulatory measures in the Japanese regulatory system are of reference value to China, such as "domestic agent system for fulfilling responsibilities and obligations, comprehensive and efficient advisory services, and worldwide regulatory inspections covering the whole process".

Objective: To analyze the potential quality risks in extracting human Prothrombin Complex Concentrate (PCC) from human plasma and producing other blood products, providing risk warnings and control measures to relevant enterprises and regulatory authorities to ensure public drug safety. Methods: Through a comprehensive review of literature and practical experience, the production process and quality control of PCC extraction from human plasma, along with its combination with plasma to manufacture other blood products, were analyzed. The safety and efficacy of producing human serum albumin (HSA) and intravenous immunoglobulin (IG) through the PCC process were also assessed. Additionally, the study compared the risks associated with switching from the direct production of HSA and IG to a process involving PCC extraction and its combination with plasma from the perspectives of process parameters, personnel, equipment, documents, and regulations. Based on this analysis, control measures were proposed. Results and Conclusion: The preparation process, raw material selection, and quality control of PCC, particularly the optimization of key process parameters, are crucial for the quality of both PCC and subsequent plasma-derived products. This study provides risk warnings and relevant recommendations for enterprises and regulatory authorities to refer to through the analysis of PCC preparation process, raw material characteristics and process change risk.

Objective: To provide a basis for the promotion and application of measurement uncertainty evaluation in domestic pharmaceutical analysis, this review sorts and summarizes the measurement uncertainty guidelines on pharmaceutical analysis that can be referenced from international to national. Methods: The history of measurement uncertainty, the main evaluation methods and the scope of application of various guidelines were summarized mainly through searching, reviewing and comparing guidelines. Results: International measurement uncertainty guidelines can be roughly divided into two categories based on the different methods used to evaluate measurement uncertainty: Bottom-up approach and Top-down approach. Multiple national guidelines are formulated based on the corresponding international guidelines issued earlier, and this review also outlines the relationship between current international and national guidelines. In addition, this review introduces a series of documents on measurement uncertainty evaluation published by drug regulatory agencies in various countries and regions. Conclusion: Whether it is the guidelines related to measurement uncertainty evaluation or laboratory quality management documents, even the relevant introductions in various national and regional pharmacopoeias, they are all a summary of a large number of practices. Carefully reading the relevant content can help pharmaceutical analysts better understand and apply the measurement uncertainty evaluation, and promote its continuous development in pharmaceutical analysis.

Objective: Supervision of pharmaceuticals through sampling and testing is challenging when it comes to online marketing. Practical operations of sampling and testing need to be adapted and theory study needs to be improved for the new situation of drug regulation. Methods: In this pilot project of online sampling and testing of pharmaceuticals, we created and executed the scheme based on the features of internet pharmaceuticals shopping. Existing problems and risks were analyzed involving procedure, prescription and logistics, and practical solutions were offered. Results and Conclusion: Related legislation needs to be revised to adapt online sampling and testing, credentials of sampling and acquisition of prescription need to be standardized. We propose to check the authenticity, optimize procedure of mixed batches, and setup a dynamic inspection mechanism.

Objective: To study the chemical constituents of the leaves of Desmodium caudatum (Thunb.) DC., a medicinal plant of legume, in order to provide material basis for the establishment of quality standard system for D. caudatum. Methods: After the leaves of Desmodium caudatum (Thunb.) DC. were extracted by 70% ethanol, the chemical constituents of the leaves of D. caudatum were separated and purifi ed by macroporous adsorption resin column chromatography, silica gel column chromatography, and preparative high performance liquid chromatography (HPLC), and their structures of the compounds were identifi ed according to the physicochemical properties and spectral data of the monomers obtained. Results: Thirteen compounds were isolated from the leaves of D. caudatum, these compounds were identifi ed and identifi ed from the leaves of Desmodium caudatum (Thunb.) DC.: desmodol (1), citrusinol (2), 8-prenylquercetin (3), dihydrokaempferol (4), neophellamuretin (5), yukovanol (6), quercetin (7), kaempferol (8), vitexin (9), swertisin (10), soyasapogenel B (11), hibiscone A (12) and hibiscone D (13). Among them, compounds 7, 8, 12 and 13 were the constituents contained in various medicinal parts of D. caudatum. Conclusion: Compounds 7, 8, 12 and 13 can be used as candidate quality control onstituents of D. caudatum.

Objective: To explore the coping strategy to the full process production site supervision of the entrusted enterprise by Marketing Authorization Holder (MAH) under the new situations. Methods: By combing the extension inspectd of entrusted production enterprises outside the province by pharmaceutical contract manufacture (hereinafter referred to as the B-certificate) MAH in Guangdong Province, the problems and reasons for the full process production site supervision of the entrusted enterprise were deeply discussed, and the corresponding improvement suggestions were put forward, according to the quality management of drug production and the relevant provisions on strengthening the management of holders after listing. Results: After combing the status of entrusted production extension inspections, it was found that three aspects problems of holders about key personnel configuration, understanding of the entire process supervision and production risk assessment, which were manifested in the lack of rich work experience of personnel, the lack of rigorous supervision methods throughout the entire process, and the incomplete assessment of production risks. Conclusion: The B-certificate MAH should focus on key personnel to fulfill their main responsibilities, improve management processes to standardize supervision behavior, strengthen risk assessment to identify safety hazards, so as to ensure the number and qualifications of key personnel match the production scale, form a closed-loop quality management system for the entire production process, carry out comprehensive and precise risk assessment, and firmly establish awareness of drug quality and safety.

Objective: To refine and elaborate on typical types of change-related issues and specific cases, based on China’s post-marketing change management framework for drugs, providing a reference for marketing authorization holders to establish a robust post-marketing change control system and offering guidance for post-marketing change inspections of drugs. Methods: Using a literature review approach,keywords such as drug management, drug change, and post-marketing changes in pharmaceuticals were used to search on the official websites of the National Medical Products Administration (NMPA), the Center for Drug Evaluation (CDE) of NMPA, and provincial medical products administrations. A series of drug change regulations issued in China in recent years were sorted out, and the framework for drug change management in China was summarized. Statistical analysis was conducted on the drug change control deficiencies raised in FDA warning letters from 2021 to 2023. Additionally, based on the author’s recent inspection experiences, typical types of issues and specific cases related to post-marketing change management in China were identified through a survey research method. Results: China’s framework for drug change management is basically well-established. However, inspections of drugs conducted both domestically and internationally have uncovered deficiencies in the post-marketing change management by drug marketing authorization holders. These deficiencies include imperfections in the establishment of a change control management system, inappropriate categorization of change management, failure to submit supplementary applications, filings, or reports as required, exclusion of changes from the change control management system, and inadequate or insufficient research on changes. Conclusion: Marketing authorization holders should establish a scientific and reasonable internal change control system, conduct necessary research on changes, and utilize the communication mechanisms of regulatory authorities to fully discuss uncertain change categories. Drug inspectors should focus on knowledge management and summarizing inspection experience to form a systematic and comprehensive understanding of changes, and conduct targeted analysis of post-marketing change issues encountered during inspections.

Objective: To conduct the in vivo toxicity study of repeated administration of oncolytic virus drug HSV-1/hPD-1 in cynomolgus macaques, and to find out the safety dose range, so as to provide informative references for subsequent clinical trials. Methods: Thirty cynomolgus macaques were randomly divided into three groups including control group, HSV-1/hPD-1 low and high-dose groups (1.0×10⁸ , 4.0×10⁸ pfu), with five animals per sex per group. The monkeys were intramuscularly injected twice a week for consecutive six weeks following an eight-week recovery phase. Animals were observed clinical symptoms daily and irritation of injective sites on days 1 and 2 post injection. Body weight was measured once weekly and food consumption was visually estimated daily. Other toxicological parameters including safety pharmacology (body temperature, blood pressure, electrocardiogram), clinical pathology (hematology, coagulation, biochemical, urinalysis), immunology (T lymphocyte, cytokine, immunogenicity), histopathology and organ weight were scheduled to be detected at the quarantine period, after the fi rst dosing, the end of dosing and recovery period. Results: All animas tolerated well and didn’t show obvious changes in clinical signs, injective irritation, body weight, food consumption, and pharmacology and clinical pathology indexes. On day 41, increased CD3⁺ CD4⁺ T lymphocytes were inspected in low dose animals. From days 13 to 97, antibody against HSV-1 vector, expressed PD-1 protein and antiantibody were continuously detected in low and high dose animals, which were considered correlation with immunostimulation and immunogenicity attributed to test articles. The histopathological fi ndings were recoverable minimal to moderate mixed cell infiltration in injection site of low and high dose animals and unrecoverable minimal myelin/axonal damage in sciatic nerve of high dose animals. The change of organ weight wasn’t detected in both groups. Conclusion: After repeated administration of oncolytic virus drug HSV-1/hPD-1, cynomolgus macaques showed good tolerance in vivo, and the no-observed-adverse-eff ect-level (NOAEL) of the test substance was 1.0×10⁸ pfu. Our research data could be used to support subsequent clinical trials.

Objective: To investigate the component biomass and its distribution characteristics of Calophyllum membranaceum, a unique traditional Chinese medicine in Guangxi, and to deeply understand the growth characteristics of plants, so as to provide a theoretical basis for the subsequent large-scale breeding. Methods: Based on plant specimens information and relevant literature review, 10 survey points which covering 8 cities and counties were set up in Guangxi to conduct the resource distribution of Calophyllum membranaceum. In each survey point, more than 3 whole plants were randomly selected and whole-plant harvest method was used to obtain plant growth indexes and biomass data. The relationship between plant organ biomass distribution and geographical and growth factors was explored at the individual level, and the growth indexes differences between wild plants and cultivated plants were compared. Results: Statistical analysis of the data from the resource survey revealed that the wild populations of Calophyllum membranaceum showed a sporadic distribution pattern and mostly grew in the lower part of the forest stand; compared with the cultivated plants, the averaged age, averaged ground diameter, averaged plant height, averaged total biomass of Calophyllum membranaceum were respectively (14.47±1.74) a, (8.28±0.53) mm, (75.68±5.10) cm, and (43.31±5.96) g. The above growth indexes were much lower than those of the cultivated plants; in terms of biomass allocation characteristics, the plant stem biomass was the largest (56.48 ± 18.79) g , and the stem mass ratio was more than 35%, while the difference between leaf mass ratio and root mass ratio was not significant. By analyzing the effects of geographic environmental factors and plant growth parameters on biomass allocation, it was found that the root shoot ratio was significantly positively correlated with altitude, the root biomass fraction was significantly negatively correlated with plant height, the stem biomass fraction was significantly positively correlated with latitude, ground diameter, plant height and age, and the leaf biomass fraction was significantly negatively correlated with the other five factors except altitude. The overall explanatory power of geographical factors on biomass allocation was 23.2%, slightly higher than growth parameters (19.6%). Conclusion: Calophyllum membranaceum populations are widely distributed in Guangxi, the plant growth is stable, but the total resources are gradually decreased. There are significant spatial geographical differences in component biomass and its allocation. The biomass allocation is influenced by others factors besides geographical factors and growth factors.

Objective: To sort out the similarities and differences of the implementation documents of the policy of wholesale and retail integration of drug business in 12 provinces, including Jiangsu, Guizhou, Hainan, Shanxi, Chongqing, Shandong, Jiangxi, Inner Mongolia, Guangxi, Guangdong, Hunan and Hubei, so as to provide references for drug business enterprises and relevant regulatory authorities and promote the high-quality development of the industry. Methods: From the policy implementation document release time, subject requirements, drug business license issuance methods, quality management system, institutions and responsibilities, personnel requirements, facilities and equipment requirements, computer system requirements and other aspects of the above-mentioned local drug business wholesale and retail integration policy implementation documents for detailed comparative analysis. Results: It is clear that the implementation documents of the policy of the integration of drug business wholesale and retail in the above provinces require the integrated wholesale and retail enterprises are the same legal entity, but there are differences in the requirements of drug business license issuance, quality management system, institutions and responsibilities, personnel requirements, facilities and equipment requirements, computer system requirements and other aspects. Conclusion: Through a comparative analysis of the implementation documents of the above-mentioned drug wholesale and retail integration policies in various places, suggestions for the development of enterprises are put forward to provide strong support for the development of the industry.

Objective: To explore more scientific and efficient methods for conducting drug pre-approval inspection under newly-revised Provisions for Drug Registration and other series of regulations and technical requirements, provide reference for the high-quality development of drug pre-approval inspection in China. Methods: By reviewing the development history of drug pre-approval inspection in China and the new changes in drug pre-approval inspection under new regulations, this study analyzes the challenges faced by drug pre-approval inspection in China under the new situation and explores corresponding strategies. Results: Under the new regulations, there have been changes in drug pre-approval inspection, including the work to be organized and carried out by CFDI, initiation mode adjusted from mandatory inspections to risk-based initiation, inspection procedure adjusted from series to parallel, organizational form adjusted from organized by NMPA and drug administration of province respectively to joint inspection, establish evaluation and inspection sub-centers, and special drug inspection center; under the new situation, drug inspection faces challenges in initiation program and procedure of inspection, construction of inspector team, collaboration and risk transmission mechanisms, applicant's registration quality and risk management awareness. Conclusion: It is recommended that regulatory agencies further refine initiation program and procedure of inspection, improve effective communication mechanisms and form a closed-loop management system for risk identification, transmission, and control, strengthen the construction of the inspector team and enhance the professional level of inspectors. At the same time, it is recommended that drug registration applicants should enhance the awareness of the first person in charge, improve quality of drug research and development application and risk awareness, actively cooperate with the work of inspection and strengthen the key competitiveness. The ultimate goal is to enhance the comprehensive strength of drug pre-approval inspection in China.

Objective: To provide reference through comparative research and analysis of regulations, for improving China's drug clinical trials and change management during clinical trials, especially for the sponsor change or production site change, and their change management during clinical trials. Methods: The regulatory requirements and implementation of European Union(EU) drug clinical trial applications and change management during clinical trials were collected and studied. Suggestions were provided by comparing them with the present regulatory framework and situation of China. Results and Conclusion: In EU, the clinical trial sponsors and clinical trial drug production sites are allowed to apply for registration and change of clinical trials both domestically and internationally. The EU clinical trial regulatory system is relatively mature and complete which are of reference value to China, such as a unified clinical trial application portal website and clinical trial information database, an integrated system of scientific and ethical in parallel review procedures, the qualification and responsibility for the sponsors and their legally designated representatives, and measures of supervision and risk control for production sites of investigational drugs as well as their changes.

Objective: To summarize the clinical trials of chemical modified new drugs that have been published, in order to provide a reference for the subsequent clinical trials of chemical modified new drugs. Methods: Based on drug clinical trial registration and information publicity platform of the Center for Drug Evaluation of National Medical Products Administration and combined with third-party databases such as Yaozhi and Insight, the clinical trial in for mation of chemically modified new drugs during the period from January 1st, 2020 to December 31th, 2023 was retrieved, and statistical analysis was conducted using excel and other method to study the development of clinical trials. Results: From January 1st, 2020 to December 31th, 2023, the number of clinical trials announcements of chemical modified new drugs had increased year by year, and a total of 548 announcements had been made in three years. Clinical trials for 2.2 types of chemical modified new drugs accounted for more than 50%, which was the highest, and clinical trials for 2.1 types of chemical modified new drugs accounted for the least. The stages of clinical trials were mainly phase I clinical trials. Conclusion: The chemical modified new drugs can draw on the clinical development data of the marketed products, reduce part of the clinical trial research, and shorten the research and development cycle, which is the hot spot of new drug research and development.

Objective: To establish the identifi cation method with specifi city for Calophyllum membranaceum Gardn. et Champ. Method: A comparative study was carried out on Calophyllum membranaceum Gardn. et Champ and its congener Calophyllum antillanum Britt and Calophyllum inophyllum L to determine the identification characteristics of Calophyllum membranaceum Gardn. et Champ by using the characteristics, microscopic thin-layer chromatography (TLC) methods. Results: The character identification of Calophyllum membranaceum Gardn. et Champ was that the leaves were oblong lanceolate and hairless on both sides. The leaves of Calophyllum antillanum Britt. were rectangular round to oval, both main veins and branchlets were densely rusty-red pilose. The Calophyllum inophyllum L. leaves were broadly oval or obovate oval, hairless on both sides. The microscopic characteristics of Calophyllum membranaceum Gardn. et Champ powder could be observed leaf epidermal cells, fi bers and so on, no non-glandular hairs. More non-glandular hairs could be seen in Calophyllum antillanum Britt. The vertical wall of the lower epidermal cells of Calophyllum inophyllum L. leaves was wavy curved and thickened in a bead shape. The TLC identifi cation results showed that there was one more characteristic spot than other varietiesin the same genus. Conclusion: The established method for the identifi cation of Calophyllum membranaceum Gardn. et Champhas special property, which could distinguish between genuine and mixed counterfeit goods of Calophyllum membranaceum Gardn. et Champ.

Objective: To obtain the potential active ingredients and protein targets of Ligularia hodgsonii Hook. in the treatment of cough, and to explore the possible mechanism of action by Network Pharmacology. Methods: The chemical constituents of Ligularia hodgsonii Hook. were retrieved from PubMed and other data platforms, then the potential targets screened out through SwissADME and SwissTargetprediction. Cough related targets were obtained by using GeneCards. Key targets were obtained from STRING and Cytoscape, which were used to construct and analyze PPI network. Metascape platform was used for GO biological function process and KEGG metabolic pathway enrichment analysis. Results: Total of 23 key targets was obtained by multi-platform analysis, and most of the corresponding components were eremophilane-type sesquiterpenes. GO analysis obtained biological processes such as positive regulation of protein phosphorylation and regulation of inflammatory response, cellular component such as cell membrane and synapse, molecular function such as protein kinase binding and protein domain specifi c binding. The results of KEGG enrichment showed the signal pathways related to infl ammation.Conclusion: Ligularia hodgsonii Hook. has many active ingredients, which may improve cough symptoms and functions via multi-component multi-target manner and multi-pathway. The underlying mechanism may involve related pathways of infl ammation and immunity.

Objective: To put forward improvement suggestions in view of the risks arising in the process of online drug sales. Methods: Combining the current development status of online drug sales and the regulatory situation of existing laws and regulations, an empirical analysis of various issues that need to be improved throughout the entire process of online drug sales was conducted. Results: In view of the current problems that there are many risk points exposd in the process of online drug sales, and to enhance compliance of online drug sales with current regulations and address operational loopholes, it is imperative to refine regulatory requirements, improve corporate management practices and strengthen social collaboration. Conclusion: Quality control of the entire process of online drug sales could guarantee the continuous compliance of the process of online drug sales, ensure the safety and effectiveness of the process of drug use, and better protect public health.

Objective: To review the development of national drug standard material label management and explore ways for improvement. Methods: The development of national drug standard material label management was reviewed, existing problems were analyzed, and a scientific and intelligent management strategy was proposed based on international experiences and technology trends. Results and Conclusion: After more than three decades of development, national drug standard material label management has achieved a leapfrog development from 3 varieties in 1956 to more than 5000 varieties in 2024 through improving the technical review system, optimizing the production process, and strengthening stability research. However, there are still problems such as label contents and forms, printing equipment and technologies, and information management system. By optimizing label contents and forms, introducing RFID technology, and drawing on international advanced experiences and standards, the transition of label management from standardization to intelligence is achieved. Drug standard material label management is an important part of ensuring drug quality and safety. Scientific, intelligent, and international management should be continuously promoted to provide solid and strong support for building a solid line of defense for drug quality and safety.