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目的证明总有机碳(total organic carbon,TOC)检测法可用于无细胞百日咳疫苗生产中的清洁验证,评价清洁方法的有效性。方法对TOC检测法的线性、精密性(重复性及中间精密性)、准确性、检测限(LOD)和定量限(LOQ)、耐用性进行验证。取不同碳浓度(20、40、80 ppm)的无细胞百日咳精制品稀释液,分别滴于玻璃、不锈钢、硅胶及塑料4种样板的表面,采用擦拭和淋洗两种方式取样,进行TOC检测,计算残留物回收率。采用TOC法对无细胞百日咳疫苗生产用具清洁效果进行评价。结果蔗糖浓度在0.25~8 mg/L范围内,与TOC值呈良好的线性关系,线性回归方程为y=1.071 7 x-0.206 3,R~2=0.999 8;重复性及中间精密性RSD值均<10%;准确性的平均回收率为99%,RSD为2.07%;超纯水的LOD及LOQ分别为24.1和80.2μg/L,棉签的LOD及LOQ分别为56.8和189.4μg/L;供试品溶液于常温下放置0、4、8、12、16、20、24、48 h后的TOC值呈逐渐降低趋势,RSD为5.66%;4种材质的淋洗和擦拭取样检测结果的RSD均<15%,回收率均在50%~120%之间。无细胞百日咳疫苗生产器具经擦拭和淋洗取样检测的残留量均≤1.5μg/cm~2。结论 TOC法可用于无细胞百日咳疫苗生产的清洁验证,证明在百日咳生产过程中所使用的清洁方法是有效的,该方法可广泛用于疫苗生产中的清洁验证。
Objective To demonstrate that the total organic carbon (TOC) assay can be used for the cleaning validation of acellular pertussis vaccine and evaluate the effectiveness of the cleaning method. Methods The linearity, precision (repeatability and intermediate precision), accuracy, limit of detection (LOD), limit of quantitation (LOQ) and durability of TOC method were tested. The acellular pertussis extract dilutions of different carbon concentrations (20, 40, 80 ppm) were respectively dropped on the surface of four samples of glass, stainless steel, silica gel and plastic. Samples were taken by wiping and rinsing for TOC detection , Calculated residue recovery. TOC method was used to evaluate the cleaning effect of acellular pertussis vaccine production tools. Results The concentration of sucrose was in the range of 0.25-8 mg / L with a good linear relationship with the TOC value. The linear regression equation was y = 1.071 7 x-0.206 3, R 2 = 0.999 8. The repeatability and intermediate precision RSD The average recovery of accuracy was 99% with RSD of 2.07%. The LOD and LOQ of ultrapure water were 24.1 and 80.2 μg / L, respectively. The LOD and LOQ of cotton swab were 56.8 and 189.4 μg / L, respectively. The TOC value of the test solution at 0, 4, 8, 12, 16, 20, 24 and 48 h at room temperature showed a decreasing trend with a RSD of 5.66%. The results of the leaching and wiping sampling of 4 materials RSD <15%, the recovery rates are between 50% and 120%. Acellular pertussis vaccine production equipment by wiping and leaching sampling residues were ≤ 1.5μg / cm ~ 2. Conclusion The TOC method can be used for the clean validation of acellular pertussis vaccine production and demonstrates that the cleaning method used during pertussis production is effective and can be widely used for cleaning validation in vaccine production.