To put forward some suggestions on post-approval change management of drugs based on ICH Q12 for our country.

The EU and China regulatory frameworks and classification requirements of post-approval CMC changes of chemical drugs under ICH Q12 were studied, and our deficiencies on management of post-approval drug changes were analyzed.

The EU has issued the Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management-Scientific Guideline, which establishes a globally recognized framework. This guideline demonstrates mature lifecycle management concepts, comprehensive management tools, clear change procedures, and efficient review communications. It enables enterprises to better understand critical elements of products and manufacturing processes through ICH Q12 tools, facilitates more efficient implementation of post-approval CMC changes, reduces corporate change costs, and conserves regulatory review resources.

China can dram on the mature experience of EU regulatory authorities to optimize its post-approval CMC change management system in accordance with ICH Q12. These measures would enhance the efficiency and scientific rigorousness of pharmaceutical post-approval CMC change management in China while alleviating burdens on marketing authorization holders (MAHs) and regulatory authorities.

The new quality of productivity is the core driving force and key support for promoting high-quality enterprise development. This study investigates the impact of the coupling and collaborative development of the talent chain, capital chain, and supply chain on the new quality of productivity of leading traditional Chinese medicine (TCM) enterprises.

Based on panel data from 75 listed TCM manufacturing enterprises from 2015 to 2023, an interactive fixed effects model is used to empirically analyze the promoting effect of the "three chains" coupling and collaborative development on the new quality of productivity of leading TCM enterprises, and further examines the mediating role of absorptive capacity.

The results show that the coupling and collaborative development of the "three chains" significantly and positively promotes the development of the new quality of productivity of leading TCM enterprises. The collaborative development of the "three chains" helps to enhance the absorptive capacity of enterprises. Absorptive capacity significantly promotes the improvement of the new quality of productivity of enterprises. Absorptive capacity plays a mediating role in the impact of "three chains" coupling and collaborative development on the new quality of productivity of leading TCM enterprises.

This research provides theoretical support for leading TCM enterprises to optimize resource allocation, enhance innovation capabilities, and improve the new quality of productivity, and offers practical evidence for policymakers to promote high-quality development in the industry.

To establish a real-time fluorescence quantitative polymerase chain reaction (PCR) nucleic acid detection method of human parvovirus B19 and validate the method systematically.

Specific primers and probes for the highly conserved regions of the three genotypes of B19 virus were designed, recombinant vectors were constructed to prepare reference-grade plasmids, and B19 quantitative amplification standard curves were established. The linear range, accuracy, precision (repeatability and intermediate precision), detection limit, specificity, genotyping and anti-interference ability of this method were verified.

When the quantitative reference range for B19 virus was 1×10⁴~1×10⁸ IU·mL^-1, a double logarithmic regression analysis was performed between the measured values and the theoretical values, and the regression equation R²≥0.980 0 showed good linear correlation. The deviation between the detection values of B19 standard substances at two concentration levels of sample 1 and sample 2 and the target values was≤±0.5 lg value. The CV values of B19 positive sample 1 and sample 2 for intra-batch, inter-batch precision confirmation and continuous repeated detection precision confirmation were both ≤5%. The detection limits of [STBX]NS1[STBZ] and [STBX]VP1[STBZ] genes were 57.8 and 5.78 IU·mL^-1, respectively, with a detection rate ≥95%. Three genotypes of B19 virus samples can be effectively detected. The plasma of seven non B19 pathogens, including hepatitis A virus, hepatitis B virus, hepatitis C virus, human immuno-deficiency virus, human cytomegalovirus, hepatitis E virus and Treponema pallidum, was non-reactive and had good species specificity. At the same time, in the presence of seven other concurrent pathogens, the positive samples were stably detected, and the B19 nucleic acid testing method was not interfered with. This method was non-reactive to common plasma interfering substances, including hemoglobin, triglycerides and conjugated bilirubin. Meanwhile, in the presence of the above three common plasma interfering substances, B19-positive specimens were stably detected, and the B19 nucleic acid detection method was not affected.

This method has strong specificity, high sensitivity, wide linear range, good stability and reliability, and high accuracy, and can be used for the detection of human parvovirus B19 nucleic acid in plasma.

To evaluate the antipyretic effect of Binafuxi Granules on dry yeast-induced fever model in rats and further explore its antipyretic mechanism, in order to provide a theoretical basis for the clinical application of Binafuxi Granules.

The rat fever model induced by dry yeast was established, and the antipyretic mechanism of Binafuxi Granules on fungal fever rats was investigated by rat anal temperature measurement, ELISA detection, qPCR detection, and Western blot detection.

The dry yeast-induced fever model experiment showed that compared with the model group, the rectal temperature of rats in each administration group of Binafuxi Granules decreased significantly in a continuous period of time (P<0.01). Compared with the model group, the contents of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in serum and the contents of prostaglandin E2 (PGE2) and cyclic adenosine monophosphate (cAMP) in hypothalamus were significantly decreased in each administration group (P<0.01). The mRNA expression levels of Toll-like receptor 4 (TLR4), cyclooxygenase-2 (COX2), nuclear factor κB p65 (NF-κB p65) and other immune and inflammatory response-related genes in the hypothalamus of rats were significantly inhibited (P<0.05). The expression levels of immune and inflammatory response-related proteins TLR4 and p-NF-κBP65 in the hypothalamus of model rats were significantly down-regulated (P<0.05).

Binafuxi Granules may inhibit the production of heat-causing inflammatory factors by regulating TLR4/NF-кB signaling pathway and exert antipyretic effect.

To improve the oral bioavailability of abiraterone acetate (ABA), reduce the administered dose, and eliminate its significant food effect.

ABA-loaded lipid nanoemulsion (ABA-NE) was prepared by high-pressure homogenization. The formulation and process parameters were optimized through single-factor tests and orthogonal experimental design. The prepared ABA-NE was characterized for particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency. A pharmacokinetic study in beagle dogs was conducted to compare the bioavailability of ABA-NE with that of the reference tablets.

The optimized ABA-NE appeared as a white, homogeneous emulsion with average particle size of (195.61±3.12) nm, PDI of (0.05±0.01), Zeta potential of -(48.17±2.64) mV, encapsulation efficiency of (95.76±1.59)% and drug loading capacity of (39.84±0.23) mg·mL^-1. The pharmacokinetic study demonstrated that compared with the reference formulation, ABA-NE significantly increased the maximum plasma concentration (C_max) and the area under the concentration-time curve (AUC). The oral relative bioavailability of ABA-NE was 16.06-fold higher than that of the reference tablets.

ABA-NE can significantly improve the oral bioavailability of ABA, which is expected to reduce the clinical dosage. It also provides a potential strategy for eliminating the effect of food. However, further experiments after meals are needed to verify this hypothesis.

To establish a flow-through cell method for determining the dissolution of tazarotene gel and analyze the correlation between its in vitro release behavior and microscopic characteristics.

A closed-loop flow-through cell system was employed to systematically investigate the effects of release medium composition, surfactant concentration, flow rate, filter membrane pore size, and fluid flow pattern on the in vitro release profile of tazarotene, while comparing the release behavior differences between commercial generic and originator products. Additionally, confocal laser micro-Raman imaging was utilized for non-destructive characterization of critical microstructure parameters including API polymorphic form and particle size distribution in both formulations, followed by analysis of key quality attributes contributing to the observed in vitro release performance disparities.

The dissolution curve with a suitable degree of distinction can be obtained by using 0.9% sodium chloride solution containing 0.5% sodium dodecyl sulfate as dissolution medium, at (32±0.5) ℃ with a flow rate of 8 mL·min^-1 and a 100 μm filter membrane. Although the polymorphic form of the active pharmaceutical ingredient (API) in generic formulations was consistent with that of the originator product, the undissolved particle counts (54 particles·mm^-2) in the generic drugs was significantly higher compared to the originator product (25 particles·mm^-2), resulting in statistically significant differences in their in vitro release profiles.

The microstructural characteristics reflect differences in the types of key solubilizing agents used as excipients in the formulation, which may influence the in vitro release properties of the product. It is recommended that domestic manufacturers promptly optimize formulation processes and improve product quality.

To detect the adverse drug event (ADE) signals of fezolinetant and estradiol to provide references for rational drug use in treatment of vasomotor symptoms (VMS) in women during menopause.

The ADE signals of fezolinetant and estradiol from the FDA Adverse Event Reporting System (FAERS) database were mined from the third-party data platform OpenVigil 2.1. The reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods were adopted to analyze and compare the risk signals of the two drugs.

A total of 72 255 adverse event reports (1 616 cases of fezolinetant and 70 639 cases of estradiol) were mined. After standardized screening, 344 cases of fezolinetant-related ADE were detected, and 33 positive signals were detected (menopausal symptoms, elevated liver function test values and postmenopausal bleeding, etc.), involving 11 system organ classification (SOC, all kinds of examinations, systemic diseases and various reactions at the administration site, and gastrointestinal system diseases, etc.). In 3 540 estradiol-associated ADE, 557 positive signals were detected (necrosis of uterine fibroids, testicular mixed germ cell tumors and pseudo-precocious puberty, etc.), covering 26 SOC classes (systemic diseases and various reactions at the administration site, product issues, and reproductive system and breast diseases, etc.). This study identified the following new potential risk signals: new ADE related to brain fog, dysarthria, oral discomfort and palpitations were discovered for fezolinetant; the SOC related to the estradiol group included benign, malignant and tumors of unknown nature, as well as those in the nervous, urinary and gastrointestinal systems.

The major adverse events of fezolinetant were associated with abnormal liver function indicators and gastrointestinal system diseases, while estradiol related ADE were associated with product use, reproductive system and breast diseases. The treatment of menopausal patients with vasomotor and other symptoms should be individualized and adverse drug reactions should be monitored.