10 February 2026, Volume 49 Issue 1
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International Journal of Biologicals. 2026, 49(1): 1-5. https://doi.org/10.3760/cma.j.cn311962-20250521-00037Objective To investigate the hemolysis and vascular irritation of human coagulation factor Ⅸ (FⅨ) products.Methods According to the provisions of the Technical Guidelines for Studies on Irritation, Sensitization, and Hemolysis of Drugs issued by the Center for Drug Evaluation of the National Medical Products Administration, for FⅨ products, the in vitro test tube method was used to evaluate the hemolytic potential of the drug, and the self-control method with left-right side of the same animal was adopted to conduct the rabbit irritation test by auricular vein injection of 1.6 mL/kg FⅨ or saline for 7 d.Results At a concentration of 50 international unit（IU）/mL, FⅨ did not induce hemolysis or erythrocyte agglutination. During the drug administration period and the recovery period after drug withdrawal in rabbits, no significant abnormalities were observed in general condition, and the vascular irritation scores were all 0. Fourteen days after drug withdrawal, the vascular irritation scores of rabbits remained 0. At 96 h after the last administration and at the end of the 14 d recovery period, the mean pathological scores of rabbits were both 0.Conclusion FⅨ at a concentration of 50 IU/mL does not exhibit hemolytic activity or vascular irritation in rabbits.
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International Journal of Biologicals. 2026, 49(1): 6-12. https://doi.org/10.3760/cma.j.cn311962-20250520-00036Objective To screen differences in abnormal toxicity test (ATT) for same biological product using animals from different suppliers and to explore the scientific and rational nature of ATT by additional blood routine analysis.Methods With reference to Chinese pharmacopoeia 2025 edition (volume Ⅲ) general rule 1141 “Abnormal toxicity test method”, the differences between animals from different suppliers were compared by analyzing the weights and blood routine results of animals after immunization with different vaccines.Results The body weight growth trend of NIH mice from supplier B was statistically significantly lower than that of the current supplier (supplier A) in both control and vaccine groups (t=2.64-7.07, all P<0.05), and the difference between suppliers C and A was not significant. Using the blood routine results of NIH mice from supplier A as a reference, blood routine results of mice from supplier B had significantly more red blood cells in both vaccine groups (t=2.44-4.07, all P<0.05) and showed significant differences in many white blood cell indicators (t=2.31-5.96, all P<0.05), while that of supplier C only showed significant differences in a few indicators. The body weight growth trends of Hartley guinea pigs from 3 suppliers (B, D, E) remained the same in both control and vaccine groups, and there was no significant difference in blood routine results.Conclusions NIH mice from supplier B have significantly different quality from those from suppliers A and C, while the quality of Hartley guinea pigs from suppliers B, D, and E is similar. The difference in animal quality directly affects the determination of ATT results, and the rationality of using ATT as a testing method for vaccine batch release is worth exploring.
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International Journal of Biologicals. 2026, 49(1): 13-20. https://doi.org/10.3760/cma.j.cn311962-20250331-00019Objective To evaluate the non-clinical safety comparability of Reassortant Rotavirus Vaccine, Live, Oral, Hexavalent (Vero Cell) produced in pilot and commercial facilities by assessments of single- and repeated-dose toxicity.Methods SD rats were administered by gavage with vaccines produced in pilot and commercial facilities, respectively, at 6 mL dosage, while the proposed clinical dosage was 2.0 mL. The long-term toxicity of the vaccine was assessed through 4 repeated intragastric administrations at doses of 2 or 6 mL per rat on day 1, 15, 29, and 43, with a 4-week recovery period. Results In the single-dose toxicity test, maximum tolerated dose was 6 mL per rat for vaccines produced in both facilities, which was 50-200 times the intended human dose converted by body weight. The body weight gain from day 0—14 and mean daily food intake of rats that received vaccines produced in pilot and commercial facilities were simliar to control groups， which were 33-44 g and 18-20 g, respectively, for female rats and 109-123 g and 25-29 g, respectively, for male rats. In the repeated-dose toxicity test, the no-observed-adverse-effect level was 6 mL per rat. The trends of body weight, mean daily food intake and body temperature in low- and high-dose groups with vaccines produced in pilot and commercial facilities were all simliar to control groups. The blood and biochemical indicators of animals did not show abnormal changes related to different facilities.In equivalent dose vaccine satellite groups, there were no statistically significant differences in seroconversion rate (P=0.474-1.000) and geometric mean titer (GMT) (t=0.05-0.85,P=0.442-0.965) of serum IgG antibodies against rotavirus, and the change trend was consistent. The peak of IgG antibody seroconversion rates and GMTs (1∶lgx) in low- and high-dose vaccine (produced in pilots facilities) satellite groups were 80.0%, 80.0% and 1.61,1.81, while the corresponding vaccine （produced in commercial facilities） satellite groups were 90.0%,100.0% and 1.79,1.91,respectively. The organs and histopathological sections of animals did not show abnormal changes related to different facilities.Conclusion Reassortant Rotavirus Vaccines, Live, Oral, Hexavalent (Vero Cell) produced in pilot and commercial facilities both show good safety in SD rats and are comparable in single-and repeated-dose toxicity studies.
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International Journal of Biologicals. 2026, 49(1): 21-25. https://doi.org/10.3760/cma.j.cn311962-20250218-00012Objective To compare the digestive effects of trypsin and trypsin-like enzyme TrypLE on Vero cells, 2BS cells, and MDCK cells, in order to determine their suitability for cell culture and digestion processes.Methods After trypsin solution and TrypLE were used to digest Vero cells, 2BS cells, and MDCK cells, key parameters such as digestion time, dispersion effect, residue after digestion, cell count, and cell viability were analyzed to compare the effects of different digestive enzymes. Digested cells were then inoculated into cell factories and basket bioreactors for cultivation. During the cultivation period, cell morphology and confluence in cell factory were observed daily, and the adhesion effect of cells and glucose consumption in basket bioreactor were measured.Results There were no statistically significant differences in digestion time, cell count, or cell viability of Vero cells and 2BS cells between trypsin and TrypLE digestions (t=﹣0.46-3.46, P=0.074-0.885), and dispersion effect and residue after digestion were similar. However, the digestion time for MDCK cells using TrypLE was statistically significantly longer than using trypsin (t=13.28, P＜0.01), and the digestion effect of TrypLE was inferior to that of trypsin. When these 3 types of cells were re-cultured in the cell factory after digestion, they all had regular shapes and good confluence. When re-cultured in the basket bioreactor, the adhesion rates of 3 types of cells within 3 h were all above 80%, and there was no statistically significant difference in the total glucose metabolism (t=﹣1.05-1.01，P=0.405-0.783).Conclusion TrypLE can replace trypsin for the digestion process of Vero cells and 2BS cells, while trypsin is more effective for digesting MDCK cells.
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International Journal of Biologicals. 2026, 49(1): 26-31. https://doi.org/10.3760/cma.j.cn311962-20250508-00030Objective To establish and validate an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of nonyl phenol leachable in human growth hormone (hGH) injection.Methods Referring to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use guidelines related to impurities, the safety limit of nonyl phenol was calculated. The UPLC-MS/MS method was used to determine the content of nonyl phenol leachate in hGH injection, and the linearity, specificity, limit of quantitation (LOQ), accuracy, precision, stability and robustness of the method were validated. The established method was used to detect 3 batches of hGH injection.Results The safety limit of nonyl phenol was 4.5 μg/vial. The method had a good linear relationship between peak area and concentration in the nonyl phenol concentration range of 8.2-65.5 μg/L.No nonyl phenol was detected in the blank solution.The LOQ was 1.2 μg/vial.The average recoveries of spiked samples at low, medium and high levels were all between 70%-125%, with relative standard deviations (RSDs) all ＜15%.The RSDs of repeatability and intermediate precision were both ＜15%.Nonyl phenol in the test solution was stable at room temperature for 20 h; when the flow rate in the chromatographic conditions was set to 0.27 and 0.33 mL/min, the RSD of nonyl phenol peak area in 6 detections was ＜10%.The detection results of 3 batches of samples were much lower than the limit of 4.5 μg/vial.Conclusion UPLC-MS/MS method for the determination of nonyl phenol leachate in hGH injection is successfully established, and the linearity, specificity, LOQ, accuracy, precision, stability and robustness of this method are good.
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International Journal of Biologicals. 2026, 49(1): 32-39. https://doi.org/10.3760/cma.j.cn311962-20250320-00017Objective To establish, verify and preliminarily apply a real time fluorescent quantitative reverse transcription PCR (RT-qPCR) detection method for xenotropic murine leukemia virus (X-MuLV). Methods Specific primers were designed according to gene sequence of X-MuLV provided by American Type Culture Collection. Recombinant plasmid and RNA standard containing target sequence were constructed, quantified through digital PCR and serially diluted to establish RT-qPCR method. Sensitivity, specificity, accuracy, precision, and robustness of RT-qPCR were investigated. The method was applied to validate virus clearance procedure by nanofiltration and chromatography, and compared with cytopathic effect assay.Results The established RT-qPCR detection method for X-MuLV showed a linear range of 2.5×101-2.5×108 copies/μL，and the amplification efficiency was 98%. The sensitivity of detection was 2.5×101 copies /μL. No cross-reaction with other commonly used viruses in the lab was detected. The coefficients of variation of repeatability and intermediate precision validation were all less than 1%. Protein and buffer had no matrix effect on virus detection of samples. When the method was employed to access the X-MuLV clearance of nanofiltration process, >4 lg copies reduction was shown in virus load between pre- and post-treatment, consistent with the result of cytopathic effect assay. When applied to evaluate composite cation-exchange chromatography, the RT-qPCR method detection results reflected the distribution of X-MuLV particles throughout the process.Conclusion The RT-qPCR method established for X-MuLV has good sensitivity, specificity, accuracy, precision and robustness, applicable for virus clearance processes validation of biological products.
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International Journal of Biologicals. 2026, 49(1): 40-44. https://doi.org/10.3760/cma.j.cn311962-20241113-00077Objective To investigate the epidemiological characteristics and breakthrough cases of varicella in Xuancheng City, and provide a basis for epidemic prevention and control.Methods The information of varicella cases in Xuancheng City from 2021 to 2023 was collected through the varicella epidemic report card of China Information System for Disease Control and Prevention, and the epidemiological characteristics were analyzed by descriptive epidemiological method.Results A total of 6 979 varicella cases were reported in Xuancheng City from 2021 to 2023, with an average annual reported incidence rate of 93.44 per 100 000 (χ2=122.80, P＜0.001). The incidence of varicella had significant seasonality, with a small peak from May to July and the highest peak from October to January of the following year. The three counties (cities) with highest average annual incidence rates were Jixi County, Ningguo City, and Jingxian County.The number of male cases was slightly higher than that of female cases, the age of onset was mainly under 14, and occupations were mainly students and kindergarteners.There were 2 652 breakthrough cases, accounting for 38.00% of the total cases. There were more breakthrough cases in males than in females, and the proportion of breakthrough cases in autumn was the largest. In 11 years after vaccination, longer time since vaccination was associated with more breakthrough cases.Breakthrough cases in clustered epidemic accounted for 68.45% of related cases, significantly higher than that in sporadic cases. Breakthrough cases were mainly students aged 7-13.Conclusions The incidence of varicella in Xuancheng City is on the rise, and schools and kindergartens are the key places for the prevention and control of varicella. It is nessesary to prevent the occurrence of cluster epidemic, increase 2-dose varicella vaccination, and reduce the occurrence of breakthrough cases. CDC should strengthen epidemic monitoring, review epidemic report, carry out targeted training and health education, and establish effective immune barriers to reduce the incidence of varicella.
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International Journal of Biologicals. 2026, 49(1): 45-51. https://doi.org/10.3760/cma.j.cn311962-20250825-00069Objective To analyze pathogens, severe cases and population distribution characteristics of hand foot mouth disease (HFMD) after the launch of inactivated enterovirus A71 (EV-A71) vaccine in China, and to provide references for the prevention and control of HFMD in China.Methods The literature published openly from 2016 to 2025, explicitly involving the application effect evaluation of EV-A71 vaccine and containing basic data such as the changes of pathogens before and after the application of vaccine, severe cases or incidence rates, and population distribution characteristics, was collected from China National Knowledge Infrastructure and comprehensively analyzed by chi-square test.Results The population distribution of HFMD cases before and after the use of EV-A71 inactivated vaccine showed that scattered children accounted for the highest proportion, followed by children in kindergartens and nurseries, and students and other groups accounted for the lowest proportion. However, after the application of EV-A71 vaccine, the composition of scattered children in HFMD cases decreased by 11.35% compared with that before the vaccine application, the proportion of children in kindergartens and nurseries increased by 25.62%, and the proportion of students and others increased by 61.38%. The differences in population distribution before and after the vaccine application were all statistically significant (χ2=15 659.45, 11 028.25, 3 587.36; P<0.001). After the application of EV-A71 vaccine, the average number of HFMD cases caused by EV-A71 decreased by 56.17%, while the average number of cases caused by coxsackie virus A16 (CVA16) and other enteroviruses increased by 8.08% and 62.37%, respectively, and the differences were all statistically significant (χ2=41.94, 310.80, 39.37; P<0.001). Non-EV-A71 enteroviruses (such as CVA16, CVA6 and CVA10, etc.) became dominant pathogens. After the application of vaccine, the average number of severe cases decreased by 42.70%, and the proportion of those caused by EV-A71 in severe cases dropped by 17.89%. The differences were statistically significant (χ2=4 087.32, 4 215.92；P< 0.001). However, approximately 59% of severe cases were still caused by EV-A71 infection after the use of the vaccine, suggesting that EV-A71 remained the main pathogen leading to critical HFMD.Conclusion EV-A71 vaccine has significantly reduced the incidence of severe HFMD cases, but EV-A71 remains the primary pathogen causing severe cases, while non-EV-A71 enteroviruses have become dominant pathogens.
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International Journal of Biologicals. 2026, 49(1): 52-58. https://doi.org/10.3760/cma.j.cn311962-20250225-00013Ankylosing spondylitis (AS) is a chronic autoimmune disease that primarily affects the sacroiliac joints, spine and adjacent tendons, soft tissues. The typical pathological progression of AS involves processes such as immune inflammation-driven responses, bone destruction, and new bone formation. These processes recur at same sites, ultimately leading to gradual joint stiffness and deformation. This article discusses the pathogenic mechanism， regulatory role, and current research status of IL-17 in AS, aiming to clarify the advantages of IL-17 as target in AS treatment and lay foundation for the development of IL-17-related drugs and the clinical management of AS.
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International Journal of Biologicals. 2026, 49(1): 59-64. https://doi.org/10.3760/cma.j.cn311962-20250813-00060Seasonal influenza poses a persistent threat to global public health, imposing a significant disease burden particularly on high-risk population such as the elderly, children, pregnant women, chronic diseases patients, and immunocompromised people. Although the effectiveness of existing influenza vaccines is contingent on their match with circulating strains, their protective benefits for high-risk population are well-supported by epidemiological evidence. Currently, influenza vaccination coverage in China remains considerably lower than developed countries. There is an urgent need to enhance vaccination rates among high-risk population through policy support and technological innovation to reduce the disease burden of influenza. This article systematically reviews the protective evidence of influenza vaccines in high-risk population, focusing on the effectiveness and applicability of different vaccine types (inactivated, live attenuated, recombinant protein, and adjuvanted vaccines) in the high-risk population. It also examines the effects of repeated vaccination, the role of herd immunity, and the optimization of vaccination strategies, providing references to improve protection in high-risk population.
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International Journal of Biologicals. 2026, 49(1): 65-69. https://doi.org/10.3760/cma.j.cn311962-20241212-00086As an important nucleic acid quantification technology in molecular biology, digital PCR has been widely used in the fields of pathogen detection, gene editing detection, and disease diagnosis in recent years due to its advantages of high sensitivity, accuracy, and specificity. This article reviews the basic concepts and principles of digital PCR, as well as the application progress of digital PCR in the field of biological detection, in order to provide a reference for researchers to choose appropriate detection methods.
创刊：1978年10月
主管：中华人民共和国国家卫生健康委员会
主办：中华医学会
上海生物制品研究所有限责任公司
编辑：《国际生物制品学杂志》编辑委员会
出版：《中华医学杂志》社有限责任公司
ISSN 1673-4211
CN 31-1962/R
主管：中华人民共和国国家卫生健康委员会
主办：中华医学会
上海生物制品研究所有限责任公司
编辑：《国际生物制品学杂志》编辑委员会
出版：《中华医学杂志》社有限责任公司
ISSN 1673-4211
CN 31-1962/R
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