Experimental Evaluation On A Vaccine Vial Monitor Developed In China For Monitoring Vaccine Temperature

Objective:1.To evaluate whether the end point of response time of a Vaccine Vial Monitor(VVM)developed in China(VVMD)meet the World Health Organization(WHO)product criteria.2.To evaluate the adaption of different specifications of VVM developed in China between the color change of those VVMs with corresponding vaccine titers under different temperature and duration.Methods:1557 VVMDs and 120 Imported VVMs and 24 bivalent Oral Polio Vaccines(bOPV)and 72 Measles-Mumps-Rubella Vaccines(MMR)and 21 Japanese B encephalitis Vaccines(JEV)were randomly sampled in this experimental study.VVMDs were exposed to water bath at 37℃ and 25℃.We measured and collected color change and analysis whether the end point response time meet WHO criteria by confidence interval method.VVMDs were assembled after made 0,1,2,3,5 months storage in room temperature condition,and two independent samples t-test and Analysis of Variance(ANOVA)was used to compare end point response time difference and compared with the WHO criteria.The end-point response time and equivalence of domestic and imported VVM of the same specification were evaluated and compared with the WHO standard Under laboratory conditions.Different specifications of VVMDs were adapted by Combining the thermal stability of the vaccines.VVMD2 corresponded to bOPV,WMD7 corresponded to MMR,VVMD 14 corresponded to JEV.The VVMDs were added to the corresponding vaccine bottle,and placed them at the specified temperature for a certain period of time,measured the correlation between the vaccine titer and the color difference of the Chinses VVM titer,and evaluate the color difference change and the corresponding vaccine titer through the Person correlation analysis VVMD adaptability.Results:1.The end point response times of VVMD2.VVMD7and VVMD14 monitors in 37℃ were 2.12(95%CI:2.10-2.15)days,6.27(95%CI:6.21-6.32)days,and 13.55(95%CI:12.02-12.26)days,respectively.Average end point response times in 25℃were12.82(95%CI:12.68-12.96)days,28.91(95%CI:28.52-29.30)days,and 76.71(95%CI:75.94-77.47)days.VVMD7 and VVM14 meet WHO criteria.The VVMD2 did not meet the WHO criteria.2.The VVMD2,VVMD7,and VVMD14 are stored at room temperature(25℃),with the extension of the storage time(0,1,2,3,5 months),the end point response time was slightly shortened.After 5 months of storage at room temperature,the end point response time of VVMD2,VVMD7,and VVMD14 were 1.99 days(95%CI:1.97 days-2.02 days),5.67 days(95%CI:5.6 days-5.73 days),12.09 days(95%CI:5.6 days-5.73 days),respectively.95%CI:11.97 days-12.21 days),VVMD2 slightly exceeds the WHO standard,VVMD7 and VVMD14 were in line with the WHO standard.3.Under the condition of 37℃ water bath,the end point response time of Chinese and imported VVMD2,VVMD7,VVMD14 were not completely equivalent.The difference between the end point response time of imported VVM2 and VVMD2 under the condition of 37℃ water bath was-0.03(95%CI:-0.08-0.02,).Under the condition of 25℃ water bath,there was a certain gap between the end point response time of VVMD2,VVMD7,VVMD14 and the imported VVM2,VVM7,VVM14.The end point response time difference at 25℃ was-2.80(95%CI:-2.80,-2.62).The end point response time VVMD2 at 37℃ was equivalent to that of imported VVM2 and VVMD2,VVMD7,and VVMD14 at 25℃ was not equivalent to that of imported VVM with O2 as the boundary value.The end point response time of VVMD and imported VVM was not completely equivalent.4.When VVMD2 reacheed the end point,bOPV type Ⅰ,type Ⅲ,and total virus titers were effective.When VVMD7 reacheed the end of the reaction,the measles,rubella,and mumps virus titers of MMR were effective;When VVMD 14 reacheed the end of the reaction,the JEV titer is still valid.The correlation between the color difference change of VVMD2 used in oral polio vaccine(bOPV)the type Ⅰ,type Ⅲ and total virus titer of bOPV was 0.52(95%CI:0.15-0.77,p<0.01),0.43(95%CI:0.02-0.71,p<0.05),0.55(95%CI:0.19-0.78,p<0.01).The correlation between the color difference of VVMD7 and the titer of measles,mumps and rubella triple vaccine was 0.59(95%CI:0.268-0.79,p<.0001),0.69(95%CI:0.53-0.80,p<0.0001),0.41(95%CI:0.18-0.60,p<0.01).The correlation between the color difference of VVMD14 and the titer of JEV was 0.90(95%CI:0.78-0.96,p<0.001).VVM14 had a positive correlation with JEV.Conclusion:1.Research had found that the end point response time of VVMD7 and VVMD14 meet WHO criteria,while VVMD2 wass slightly exceeds the WHO standard.2.When adapted to VVMD according to the thermal stability of the vaccine,The color difference(time temperature response)of the three specifications of VVMD was related to the change of vaccine titer When the VVMD reaches the end point,the titers of the adapted vaccine were all qualified.3.Both VVMD7,VVMD14 and imported VVM7,VVM14 meet the WHO standards,but the end point response times of VVMD and imported VVM of the same specification are different.The response time of VVMD of the same specification is different from the imported VVM in this research.4.When VVMD stored at room temperaturefor 1-5 months,the end point response times of VVMD7 and VVMD 14 were attenuated,but they meet the WHO standard.The end point response time of VVMD2 slightly exceeded the WHO standard.It was recommended to determine the suitable temperature storage conditions for VVMD.