随着全球医疗需求增长及环保意识增强，传统化学制药的高污染、高能耗等问题日益凸显。为实现可持续发展，该 文结合绿色化学理念，提出“绿色化学制药十二原则”，旨在通过技术创新与工艺优化，降低环境负担并提升资源效率。该 原则涵盖合成路径设计、能源经济性、可再生原料使用、催化反应优化、溶剂选择、智能化生产等关键环节，强调利用人 工智能技术实现工艺精准控制与流程强化。同时，倡导副产物资源化、连续化生产和药物递释系统理性设计，以减少废弃 物排放并提高药品质量。该原则不仅为制药工艺研发与生产提供指导，还将推动行业标准的制定，促进制药工业向绿色、 高效方向转型，为全球药品需求的战略满足提供科学支撑。

Doxorubicin is one of the potent drugs in the clinic for the treatment of blood cancers and solid tumors. However, side effects and drug resistance of doxorubicin pose major obstacles to its application in antitumor therapy. Curcumin exhibits multiple pharmacological effects such as antitumor activity, antioxidation, and anti-inflammation. When combined with doxorubicin, curcumin can enhance efficacy, reduce toxicity, and reverse multidrug resistance. Nevertheless, due to the poor solubility, instability, and low bioavailability of curcumin, the application of this combination therapy is limited. Currently, the nano drug co-delivery system offers numerous advantages in antitumor therapy. A nano-based co-loading delivery system of curcumin and doxorubicin can improve drug solubility, enhance stability, achieve targeted drug aggregation, and realize sustained- and controlled- release at the tumor site. This review summarizes the antitumor mechanisms of the concomitant use of curcumin and doxorubicin and their novel nano-based drug delivery systems in recent years, providing ideas for further research on this combination therapy and the development and application of their nano-formulations.

In this study, a novel synthetic process of finerenone(1), an anti-diabetic nephropathy drug, was developed. Using 2-hydroxyethyl methyl sulfone(20) and 2,2,6-trimethyl-4H-1,3-dioxin-4-one(21) as starting materials, the target product 1 was synthesized through sequential steps including alcoholysis, Knoevenagel condensation, Hantzsch cyclization, etherification, chiral resolution, β-elimination, and ammonolysis, with an overall yield of 19.9％ (based on 20), purity of 99.80％ , and ee value of 99.82％ . The novel process features mild reaction conditions and well-controlled quality, yielding intermediate 2-(methylsulfonyl)ethyl (4S)-4-(4-cyano-2-methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro- 1,6-naphthyridine-3-carboxylate with high optical purity following resolution, making it suitable for industrial production.

Diseases caused by bacterial infections pose a significant threat to human health. In recent years, the overuse of antibiotics has led to the emergence of drug-resistant microorganisms and the development of new bacterial strains. These factors have further exacerbated the threat of bacteria to human health and environmental safety. Consequently, the development of novel antibacterial materials to prevent the emergence of “superbugs” has become a key research focus. Metal-organic framework materials(MOFs) have emerged as star materials in the antibacterial field, owing to their exceptional crystallinity, high porosity, large specific surface area, and facile tunability through modification. However, traditional MOFs also exhibit some shortcomings, such as poor hydrophilicity, long antibacterial cycles, and lack of targeting. To overcome these drawbacks, post-synthetic modification of conventional MOFs has emerged as an important strategy. Based on this, this article summarizes several design approaches for novel MOF-based antimicrobial materials, including modification of MOFs metal nodes, functionalization of organic ligands, surface and pore structure modification, and the formation of composites with other materials. The aim is to provide a reference for the future synthesis of advanced antimicrobial MOFs.

The synthesis process of the antihyperglycemic drug linagliptin(1) was optimized, and the key process parameters for each step were determined, along with the impurities generated. Starting from 8-bromo-7-(but- 2-yn-1-yl)-3-methylxanthine(3), crude 1 was obtained through a two-step substitution reaction and deprotection. The pure target 1 was afforded by recrystallization from ethanol with an overall yield of 74.6％ (based on 3) and HPLC purity of 99.85％ , while individual impurity below 0.05％ . By replacing the deprotection reagent with trimethylsilyl trifluoromethanesulfonate(TMSOTf), the process was stabilized and simplified, significantly reducing the formation of the dimer impurity of 1(namely related substance B). This optimized process was suitable for industrial production. Furthermore, nine related substances were synthesized, among which the synthetic routes of related substances A, C, D, E, F, G, H, and I were reported at the first time. This study is expected to provide a valuable reference for the quality control of 1.

Teduglutide(1) exerts its physiological effects by binding to glucagon-like peptide-2(GLP-2) receptors on the intestinal and digestive tract walls. Clinically, it is used to treat short bowel syndrome. In light of the current situation where only an expensive original product with limited accessibility is available on the domestic market, this study aims to develop a more efficient production method. To achieve this, small ubiquitin-related modifier protein was fused with 1 for intracellular soluble expression in Escherichia coli. The results showed that the target peptide reached a productivity of over 800 mg per liter of fermentation broth, with a purification yield of approximately 46％ and a purity exceeding 99％ . The LC-MS/MS analysis confirmed that relative molecular weight and amino acid sequence of the peptide were consistent with the theoretical predictions. This research offers a simple, low-cost, high-yield approach for 1 production, laying a foundation for future large-scale manufacturing.

Reactive oxygen species(ROS) are byproducts of cellular redox metabolism. Excessive ROS can lead to oxidative damage of DNA, proteins and lipids, thereby exacerbating the genetic instability of cancer cells and promoting tumor initiation and progression. Peroxiredoxin 1(PRDX1), a key member of the peroxidase family, plays a pivotal role in maintaining intracellular ROS balance, effectively protecting cells from ROS-induced damage. Simultaneously, PRDX1 acts as a molecular chaperone in various malignancies, exhibiting dual roles in either promoting or inhibiting tumor growth. In recent years, numerous PRDX1-targeting candidate drugs have demonstrated significant antitumor effects both in vitro and in vivo, confirming PRDX1 as a potential target for cancer therapy. This review summarizes recent advances in understanding the mechanisms of PRDX1 as a tumor treatment target, as well as the development of antitumor natural products targeting PRDX1.

Dimetridazole(1) is a nitroimidazole antibacterial agent and an antiprotozoal veterinary drug. The traditional batch methylation for the synthesis of 1 has issues such as low yield, abundant disubstituted impurities, and high safety risks. In this study, 1 was prepared through a continuous flow reactor, which effectively reduced potential risks in the methylation reaction and increased the yield from 53％ (reported in the literature) to 73％ . Meanwhile, four related substances of 1 were discovered and synthesized, namely 1,2-dimethyl-4-nitro-1H-imidazole(3), 1,2,3-trimethyl-5- nitroimidazolium monomethyl sulfate(4), and a mixture of N-methyl-N-(2-methylamino-2-nitrovinyl)acetamide(5) and N-methyl-N-(2-methylamino-1-nitrovinyl)acetamide(6), which provided some references for the quality control of 1. In addition, it was found that when ammonia was used in the work-up of the methylation reaction, the quaternary ammonium salt 4 could be demethylated into the target product, offering a new approach to turning waste into valuable product.

随着人工智能、集成电路、生物医药等前沿研究的持续进步，药品先进制造数字孪生愈发受到关注。目前，数字孪 生技术已在制药行业实现了某些场景应用，并在优化布局、提升产品质量、降低成本等方面发挥积极作用，但其技术要求 以及合规考量仍需深入分析。文章围绕药品先进制造数字孪生的挑战和关注要点进行探讨，就进一步推动生物医药产业高 质量发展以及国际化进行了展望，并在技术设计和实践方面提出建议，以期为药品先进制造的科学监管以及新质生产力的 发展提供一定参考。

Low-concentration atropine eyedrops, an ophthalmic formulation for delaying myopia of adolescents, has been widely recognized due to its clinical therapeutic effects. However, the commercialized atropine sulfate eyedrops, ophthalmic aqueous solution, have many problems, such as eye irritation caused by low pH value of the aqueous solution, poor stability of the preparations and poor patient compliance. In this review, the formulations and preparation processes of atropine sulfate ophthalmic preparations currently under development and on the market are summarized, the characteristics, advantages and disadvantages of various technical approaches for improving stability and compliance of atropine sulfate ophthalmic products are analyzed, hoping to provide some references for the optimization of atropine ophthalmic formulations.

Finerenone(1) was synthesized from diketene and 4-methoxybenzylamine as the starting materials, through the aminolysis, condensation, Hantzsch cyclization, ethylation, and chiral resolution steps. After optimizing the reaction conditions, the overall yield of this process was 11.4％ with the purity of 99.7％ . The usage of 4-methoxybenzyl group as the protection group was reported at the first time in this route, which was suitable for industrial production.

Recombinant human granulocyte colony-stimulating factor(1) is clinically used to treat neutropenia caused by chemotherapy or radiotherapy in cancer patients. When expressed in Escherichia coli, 1 predominantly accumulates as inactive inclusion bodies. So, the low yield of inclusion body denaturation and refolding limits the overall process yield. In this study, soluble expression of 1 was achieved by employing a fusion expression strategy with the small ubiquitin-related modifier protein, with an expression level of 2.19 g/L. Further steps including extraction, enzymatic cleavage, clarification, anion exchange chromatography, cation exchange chromatography, and ammonium sulfate precipitation yielded 1 with a purity of 99.3％ and a recovery rate of 44.2％ . The structure and function of the self-produced 1 were confirmed through HPLC retention time comparison, mass spectrometry, peptide mapping, disulfide bond localization, and in vitro biological activity assays. Finally, a 50 L scale-up test demonstrated the feasibility of industrial-scale manufacturing for this process. This study provides a robust foundation for the industrialization and subsequent structural optimization of 1.

To enhance the solubility and dissolution rate of epalrestat(EP), a cocrystal of EP and benzamide(BAM), as well as its inclusion complex with hydroxypropyl-β-cyclodextrin(HP-β-CD), were prepared using a mechanical ball milling method. The preparation conditions for both the EP-BAM cocrystal and its inclusion complex were optimized. Structural characterization was performed using powder X-ray diffraction, differential scanning calorimetry, and infrared spectroscopy. The solubility performance was evaluated through saturation solubility experiments and in vitro dissolution tests were also carried out. The results showed that the solubility of the EP-BAM cocrystal increased by 1.08- fold compared to EP, while that of the EP-BAM/HP-β-CD inclusion complex increased by 11.53-fold. The results of in vitro dissolution tests showed that both the cocrystal and the inclusion complex exhibited superior dissolution rates and amounts compared with the physical mixture. The EP-BAM cocrystal and the EP-BAM/HP-β-CD inclusion complex significantly improve the solubility and dissolution rate of EP, providing an effective strategy to enhance its bioavailability.

Oligonucleotide drugs have been utilized in the prevention and treatment of various diseases. To enhance their stability and facilitate transmembrane delivery, lipid nanoparticles(LNPs) are commonly employed as carriers. However, the poor stability of miRNA-LNPs results in stringent storage requirements, limiting their broad application. Therefore, this study investigated the effects of formulation and process parameters on miRNA-LNPs physical stability, using particle size and encapsulation efficiency as key indicators. The results indicated that various phospholipids contributed to the physical stability of LNPs, among which PEGylated phospholipids effectively preventing LNPs aggregation. The phase transition of water directly destroyed the LNPs structure, and the combination of cryoprotectant sucrose and PEGylated phospholipids could effectively resist the damage caused by water phase transition to the LNPs structure. By elucidating the mechanisms by which structural materials and water phase transitions affect miRNALNPs physical stability, this study introduced cryoprotectants as a novel strategy to improve the physical stability of oligonucleotide drug-loaded LNPs. These findings provide valuable insights for optimizing LNP-based formulations, thereby strengthening the clinical applicability of small nucleic acid therapeutics.

An ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method was established for the determination of dictamnine(1) and fraxinellone(2) in rat plasma. A UPLC HSS T3 chromatographic column(2.1 mm×50 mm, 1.8 μm) was used, and the analysis was carried out in the gradient elution mode with acetonitrile as mobile phase A and water(containing 0.1％ of formic acid) as mobile phase B. Positive ion mode detection and multiple reaction monitoring mode were used for quantitative analysis, with midazolam as the internal standard. The results showed good linearity for 1 and 2 in the range of 2 - 2 000 ng/mL. The extraction recovery rates of 1 and 2 were above 79.5％ , the precisions were less than 15％ , and the accuracies were 87.3％ - 109.8％ . In pharmacokinetic studies in rats, after gavage administration(2 mg/kg) or sublingual administration(0.1 mg/kg), the cmax of 1 were (1 382.4±129.6) and (382.6±118.9)ng/mL, with t1/2 of (1.5±0.2) and (2.3±0.5)h, respectively; the cmax of 2 were (57.5±2.2) and (742.6± 109.7)ng/mL, with t1/2 of (2.7±1.0) and (2.1±0.5)h, respectively. The bioavailability values of 1 and 2 were 68.1 ％ and 7.6％ , respectively. This established method provides a reference for its clinical use.

A HPLC method was established for the simultaneous determination of sodium chondroitin sulfate(2), vitamin B1(3), and vitamin B6(4) in compound cerebroprotein hydrolysate tablets(1), and the content uniformity was also investigated. Chromatographic separation was performed on a Hypersil BDS C18 column(4.6 mm×250 mm, 5 μm) using gradient elution with 0.02 mol/L sodium heptanesulfonate solution as mobile phase A and acetonitrile as mobile phase B. The column temperature was set at 35 ℃ , with an injection volume of 20 μL. The detection wavelengths were set at 200, 246, and 291 nm for compounds 2, 3, and 4, respectively. The methodological research results showed that the established method exhibited strong specificity, good linearity, repeatability, and accuracy. The sample determination results showed that the content and content uniformity of the three components in 1 from different manufacturers were significantly different, indicating the necessity for enhancing its quality control measures.

Peptide-drug conjugates(PDCs) are emerging targeted drugs, composed of payloads, linkers, and homing peptides. By homing peptides, cytotoxic molecules or radionuclides can be enriched in cells of diseased tissues, thereby reducing the toxicity to normal cells. With the advantages of high selectivity, high tissue penetration, and low immunogenicity, PDCs have become a hot spot in the development of a new generation of targeted antineoplastic drugs following antibody-drug conjugates(ADCs). Nevertheless, PDCs still face some challenges, such as poor in vivo stability, and low receptor affinity. This paper reviews the composition, clinical application progress, key technologies, and challenges of PDCs, aiming to provide some references for the development and application of PDCs.

A centrifugal assisted liquid-liquid extraction combine with gas chromatography method was established for the determination of 17 related substances in sodium valproate(1) sustained-release tablets. The HP-FFAP column (0.32 mm×30 m×0.25 μm) and the hydrogen flame ionization detector were used with programmed temperature. The flow rate was 3.0 mL/min, the inlet temperature was 220 ℃ , and the detector temperature was 300 ℃ . The results showed that the established method could effectively separate 17 process impurities and degradation impurities, with a detection limit of about 0.25 μg/mL(0.005 ％ ). The impurities 2-methylvaleric acid and 2-methyl-2-ethylvaleric acid were detected in 1 sustained-release tablets by this method. This method solves the problem of difficult detection caused by material swelling and inability to dissociate in 1 sustained-release tablets and enables accurate determination of the related substances, providing a reference for the quality control and standard improvement.

Mesoporous silica nanoparticles(MSNs) have adjustable pore diameters and pore structures, high specific surface areas, as well as good biocompatibility. As a delivery carrier, MSNs can enhance drug stability, realize the controlled release of drugs, and improve the solubility and bioavailability of poorly soluble drugs. This review summarizes the advantages of MSNs as drug carriers, introduces the applications of MSNs in drug delivery and disease treatment in recent years, and anticipates the application prospects of MSNs.

文章探讨氘代药物相较于原型药物化合物专利的自由实施可能性，为药企开发氘代药物的侵权风险评估提供参考。 首先，简要梳理了我国专利侵权判定规则体系，概括了目前实践中原型药物化合物专利中权利要求和说明书的撰写方法， 最后结合氘代药物的特点，综合分析撰写方式对于氘代药物自由实施的可能影响。而评估氘代药物自由实施的可能性，一 方面需依据侵权判定的步骤和原则，另一方面需综合考量氘代药物相较于原型药物所具备的未揭示效果。

Cytotoxicity tests were conducted to evaluate the biosafety of medical polyurethane(PU) products. In this study, cytotoxicity tests of PU products mainly composed of bis(4-isocyanatocyclohexyl)methane(HMDI) and poly(tetramethylene ether)glycol(PTMEG) were conducted. The cytotoxicity of the PU products, raw materials and additives in the formulations were tested respectively according to the MTT method. The results showed that PU had no acute systemic toxicity, but the cell viability of PU was less than 50％, which indicated a cytotoxic potential. This laboratory prepared a small-batch of PU samples using the same formulation as commercial products, which passed acute systemic toxicity tests but exhibited only 8％ cell viability. After acetone cleaning, the cell viability increased to 60％ . The cell viabilities of the formulations containing HMDI and the additives such as chain extenders, antioxidants, light stabilizers and catalysts were more than 70％ in the cytotoxicity test, indicating no cytotoxicity. However, the cell viability of PTMEGcontaining formulations was less than 70％ , with viability decreasing as concentration increased, indicating that PTMEG might be the primary cause of PU cytotoxicity. It is recommended to adjust the proportion of PTMEG or replace it with polyols exhibiting superior biosafety performance in PU products, and optimize the cleaning process during production to ensure the biosafety of PU.

注射剂为临床常用的高风险剂型，特别是小容量注射剂，其灌装量对临床用药的安全性和有效性至关重要。该文结 合各国法规、指南，对小容量注射剂过量灌装的确定方法进行分析和讨论，并通过举例说明过量灌装限度确定需要考虑的 因素，以期为探索合理的、符合技术及法规要求的研究策略提供参考。

In order to meet the regulatory requirements for halide identification of pharmaceutical rubber stoppers(mainly chlorinated and brominated rubber stoppers) in packaging material changes and generic drug research and development, a rapid and accurate method based on pretreatment of ignition residue and ion chromatography detection was established. After ignition and ashing, residual ions in samples were extracted with water. The Dionex IonPac™ AS19 column was used, with 20 mmol/L potassium hydroxide solution as eluent, at a flow rate of 1 mL/min, column temperature of 30 ℃ , and injection volume of 25 μL. The results showed that it was linear for chloride and bromine ions in the range of 2 - 100 μg/mL, with satisfactory recovery and strong method specificity. The method was applied to determine 16 batches of halogenated butyl rubber stoppers from different manufacturers, and the determination results were completely consistent with the formulations claimed by the manufacturers. This simple, rapid, and accurate method enables effective identification and quantitative detection of halides in pharmaceutical stoppers, providing reliable technical support for packaging material changes of marketed drugs, generic drug packaging screening, and quality control of rubber stoppers.

In 2024, FDA approved 50 new drugs, including 31 chemical small molecules and 19 biological products. This review describes the descriptions, indications, mechanism of action, dosage forms and strengths, adverse reactions, and synthesis routes of all the small molecules, and the basic information about biological products.

In this paper, the synthetic route of phenylephrine hydrochloride(1) was improved. 3-Hydroxyacetophenone( 2) was used as the starting material to synthesize 2-chloro-1-(3-hydroxyphenyl)ethan-1-one(3) by reacting with sulfonyl chloride. Compound 3 was transformed into 1-(3-hydroxyphenyl)-2-[benzyl(methyl)amino]ethan-1-one(4) through nucleophilic substitution with N-methylbenzylamine. (R)-3-[2-[Benzyl(methyl)amino]-1-hydroxyethyl]phenol(5) was stereoselectively synthesized from 4 via reduction by the engineered bacteria containing carbonyl reductase A12. Compound 1 was obtained from 5 with the purity of 99.9％ and ee value of up to 99.9％ by palladium carbon debenzylation and salification, and the total yield reached to 62.8％ (based on 2). The improved synthetic route had the characteristics of simple operation and high yield, which was suitable for industrial production.

新药研发合作模式成为我国各大制药企业共同关注的话题。文章在改进原有竞合博弈范式基础上，采用复杂中介模 型分析了我国医药制造板块上市公司的博弈型研发合作对制药企业新药研发效率的促进机制。得出 2 条结论 ：①博弈型研 发合作有助于加快制药企业关键核心技术突破，从而显著提升制药企业新药研发效率 ；②不同博弈型研发合作的收益分配 模式，将对制药企业新药研发效率产生异质性影响。同时，提出了“市场均分型”和“股权收益型”2 种高绩效新药研发 合作模式，以期为我国制药企业突破关键核心技术、提高新药研发效率提供一定参考。

Droplet-based microfluidic technology shows great application potential in the preparation of drug delivery systems due to its excellent handling of fluids at the micro- or nano-scale. Compared with the microspheres prepared by conventional preparation methods, the microspheres prepared by droplet-based microfluidics exhibit a welldefined and controllable composition and structure, high monodispersity, and good process reproducibility. Focusing on the droplet generation passive method and passive microchannel device, this review introduces the basic principles of microsphere preparation by droplet -based microfluidics, and systematically analyzes the main effects of fluid-related parameters, device design parameters and additives on the critical quality attributes, including microsphere morphology, particle size distribution, encapsulation efficiency, and drug release behavior. It is hoped that this review can provide a reference for the research and development of microspheres.

药品上市后变更管理属于药品全生命周期管理的一部分，本文梳理了药品上市许可有关稳定性的要求及相关指导原 则，并对药品上市后有关变更事项中的稳定性要求及有效期确定进行分析。重点关注了稳定性研究中的放样条件选择、考 察指标制定和结果评价等方面的内容，对药品上市后变更稳定性研究中常见问题，结合审评实践进行了探讨，旨在为上市 后变更稳定性研究工作提供更多参考。

Biopharmaceuticals, especially therapeutic monoclonal antibodies(mAbs), are mainly produced in mammalian cell culture systems. Glycosylation is a critical quality attribute of mAbs, which has a significant impact on their biological activity, pharmacokinetics, half-life, and immunogenicity. Therefore, in order to better control the quality of glycosylation modification, the glycosylation process of mAbs must be regulated and monitored throughout the culture process of mammalian cells. This review focuses on the engineering of mammalian cells, optimization of cell culture processes and culture media, glycosylation regulators, mathematical models and omics technologies. And it introduces the technological progress achieved in the regulation of glycosylation modification of monoclonal antibodies during mammalian cell culture.

The treatment for arthritis often involves long-term oral administration or intra-articular injection of nonsteroidal anti-inflammatory drugs to alleviate inflammation and slow down the progression of the disease. However, these treatments may give rise to gastrointestinal irritation, hepatotoxicity, intra-articular infections, and other adverse effects. As a transdermal drug delivery system, microneedles can penetrate the stratum corneum barrier to deliver drugs to the deeper epidermis and dermis layer rich in immune cells, and has attracted widespread attention and application in the field of arthritis treatment due to its advantages of minimally invasive and improved drug permeability. This review elaborates on the progress of microneedles in the treatment of arthritis, in order to provide a reference for the development of preparations for arthritis treatment.

国务院于2019 年启动针对高值医用耗材的治理改革，对高值医用耗材的价格形成、医保支付、市场监管和医疗行为 等方面进行联动治理和综合性改革。高值医用耗材的定义是否需要调整，已成为当前亟须探讨的问题。基于高值医用耗材 的历年政策及现状，该文对其定义进行梳理，探讨集采降价后其是否符合“有较高价格”的说法，并从价格和价值两大角 度重新界定。研究结果显示，在当前集采背景下高值医用耗材的定义与内涵应包括2 个方面：一是价格高，二是价值高( 满 足医学、技术和社会3 个特性维度之一)。符合上述2 个方面中任一方面的医用耗材即可称为高值医用耗材。

对 FDA 微生物污染相关的药品召回事件执法报告中的制剂类型、召回原因、污染微生物种类等方面进行分析，了解 国外制药行业微生物控制的关注点，为我国药品的微生物质量控制提供参考。在微生物污染相关的召回案例中，无菌药品 召回 132 种次；非无菌药品召回 893 种次。无菌药品召回的原因主要为缺乏无菌保障 (54％ )；非无菌药品的召回原因主要 是非无菌药品微生物污染 (79.3％ )，其中洋葱伯克霍尔德菌群污染是典型代表。未明确鉴定结果的微生物污染在无菌药品 召回中占 81.8％，在非无菌药品中占 69.4％。美国的药品召回体系相对成熟，制药行业对于药品微生物质量控制不仅局限 于终产品，更贯穿至生产整个过程，值得我国借鉴。

Based on the six major systems of drug production quality management and the analysis of the typical production processes of chimeric antigen receptor T cell(CAR-T) products, this review analyzes and discusses the particularity of the CAR-T product production system and the corresponding key quality management points from four main aspects, namely product production process quality control, process validation and aseptic processing simulation test, contamination and cross contamination control in the production process, and production related deviation and change control. This review provides some references to cell therapy product manufacturers especially CAR-T product manufacturers, to further improve production system quality management, and also provides a reference to production inspection and quality audit.

口服混悬剂是为吞咽困难患者设计的一种非均相液体制剂，较其他口服制剂加入了更多种类的功能性辅料来维持体 系的稳定性及适口性，故其质量研究与控制难度大、潜在的安全性风险高。文章通过调研不同药品监管机构规定、指导原则、 药典等文件并结合药品审评经验，全面阐述如何开展该剂型的质量研究与控制，强调了易被忽略的问题，以期为业界开发 高质量的口服混悬剂提供参考。

Antibody drug conjugates(ADCs) are biotherapeutic agents composed of a monoclonal antibody covalently linked to a cytotoxic payload via a chemical linker. Their unique structure combines the dual advantages of antibody-mediated targeted delivery and the potent cytotoxicity, demonstrating remarkable clinical efficacy in solid tumors, hematological malignancies and other therapeutic areas. ADCs are expected to play a pivotal role in future global drug development. Throughout the entire lifecycle of ADC development, manufacturing, and quality control, their binding affinity and biological activity critically influence therapeutic efficacy and safety. Comprehensive characterization of in vitro biological activity not only serves as the cornerstone for ensuring the clinical performance but also drives the resolution of current technical challenges and the advancement of innovative drug development. This review systematically discusses the current in vitro biological activity evaluation methods of ADCs, focusing on five functional modules based on the mechanism of ADCs: target binding activity, internalization efficiency, payload cytotoxicity, bystander effect, and Fcmediated functions, aiming to provide methodological references for ADC development and quality control.

To investigate the effects of score design on the quality of scored tablets, five types of scored tablets were selected as models, and the effects of tablet shape, shape and depth of score line, tablet hardness on the partitioning capability of different specifications and different tablets were evaluated with tablet weight variation, mass loss, content uniformity, and dissolution/release as evaluation indicators. The results showed that capsule-shaped tablets were easier to be split than circular tablets. When the long-to-short axis ratio of the capsule-shaped tablet was less than 2, tablet weight variation could be improved by increasing the score line depth(approximately 0.5 mm). The recommended hardness range for sustained-release scored tablets was between 90 N and 130 N to maintain the integrity of the pellets; the recommended hardness range for orally disintegrating tablets was between 30 N and 50 N to meet the requirement of disintegration time limit within 60 seconds. Low dose(specification ≤ 10 mg) scored tablets should pay attention to the content uniformity of intact tablets(A+2.2S ≤ 7.0) and the mass loss( ≤ 0.8 ％ ) after segmentation to control the accuracy of tablet splitting. Manual and mechanical splitting showed no significant differences in various indicators of the segmented parts, fully complying with the requirements of Chinese Pharmacopoeia 2020 Edition and the related guidance. These findings validated the rationality of the model drug score design and provided guidance for scored tablets development.

Based on the principle that uricase catalyzes the decomposition of uric acid to produce allantoin, hydrogen peroxide and carbon dioxide, this paper established a method to detect the activity of uricase at 37 ℃ and pH 7.5. The results showed that the quantitative ranges of hydrogen peroxide and uricase were 0.049 - 100.000 μmol/L and 0.819 - 200.000 mU/mL, respectively. The within- and between-run variation coefficients of precision were less than 20.0％ , and the relative error of accuracy were within ±25.0％ . The results of recovery experiments using hyperlipemia samples(lipid index 3 mg/mL) and 2％ hemolysis donor samples compared to normal donor samples showed that hyperlipemia did not interfere with the detection of uricase activity, whereas hemolysis did. Uricase activity was not affected when human serum uricase samples were placed at room temperature or 2 - 8 ℃ for no more than 24 h, frozen and thawing for no more than 3 cycles, and stored at –70 –90 ℃ for no more than 64 days. In conclusion, the established method is sensitive, precise, accurate, simple, rapid, and can support the evaluation of preclinical and clinical studies of uricase drugs.

CD16 has the capacity to effectively mediate natural killer(NK) cell activation without the necessity for co-engagement of other receptors, making it a widely selected target in bispecific antibodies(BsAbs) based on NK cell redirection. Mesothelin(MSLN) is significantly overexpressed in various solid tumors and can promote tumor cell adhesion, migration, proliferation, and survival. In this study, a bispecific antibody, 16MSLN, targeting both CD16 and MSLN was constructed. The antibody was expressed in Expi293F cells and purified using Protein L to obtain highly pure target antibody. The results of cell experiments indicated that 16MSLN could promote the crosslinking of NK cells with target cells and specifically enhance the killing effect of NK cells on MSLN+ tumor cells. This study provides a reference for the development of NK cell-redirected BsAbs.

A novel synthetic route for the preparation of the camptothecin intermediate, the racemic lactone(17), starting from 6-chloro-2-methoxynicotinic acid(12) was reported in this paper. Initially, compound 12 underwent a nucleophilic addition reaction with the selected 1-(tert-butyldimethylsilyloxy)butan-2-one. Employing an acetal and a benzyl group for selective protection, the synthesis proceeded through oxidation, deprotection and cyclization with methylsulfonic acid. The overall yield of this process was 31.23 ％ (based on 12). Compound 17 could be effectively converted into the racemic tricyclic ketone through four additional steps. This new synthetic method successfully avoided the needs for hazardous reagents such as ozone, osmium tetroxide, and cyanides, greatly enhanced the safety.