MacDonald W D, Pelletier C A, Gasper D L
J Parenter Sci Technol. 1989 Nov-Dec;43(6):266-70.
Microbial challenge test methods to validate sterilizing-grade filters were developed to facilitate the use of parenteral drug products as liquid vehicles. Scaled-down filtration systems were developed in response to processing parameters, e.g., flow rates, pressures, duration, and temperature, provided by customers. Accordingly, 47 mm disc filter holders were chosen to minimize the volume of product necessary for each test. A peristaltic pump was used to produce positive pressure within the test system, and a 47mm filter sampling manifold was used to assay the entire filtrate. The resultant system was able to accommodate a variety of flow rates while maintaining the viability of the retention test microorganism, Pseudomonas diminuta (ATCC Number 19146). Experiments were conducted by challenging sterilizing-grade (0.22 micron) and 0.45 micron polyvinylidene difluoride (PVDF) (Durapore) filter discs under simulated processing conditions with P. diminuta resuspended in the pharmaceutical products. The challenge concentration was at least 10(7) colony forming units per cm2 of filter area. The 0.22 micron filters were shown to be retentive in all cases, while the 0.45 micron membranes exhibited some degree of bacterial passage as expected. The results of these experiments were communicated to the customers for inclusion in their process validation documentation.
为便于将肠胃外注射用药品用作液体载体，开发了用于验证除菌级过滤器的微生物挑战试验方法。针对客户提供的工艺参数（如流速、压力、持续时间和温度），开发了缩小规模的过滤系统。因此，选择47毫米的圆盘式过滤器支架以尽量减少每次试验所需的产品体积。使用蠕动泵在试验系统内产生正压，并使用47毫米的过滤器采样歧管对整个滤液进行分析。所得系统能够适应各种流速，同时保持截留试验微生物——缺陷假单胞菌（美国典型培养物保藏中心编号19146）的活性。通过在模拟工艺条件下，用重悬于药品中的缺陷假单胞菌对除菌级（0.22微米）和0.45微米聚偏二氟乙烯（PVDF）（Durapore）滤膜进行挑战试验来开展实验。挑战浓度为每平方厘米过滤面积至少10(7) 菌落形成单位。结果表明，0.22微米的过滤器在所有情况下均具有截留性，而0.45微米的滤膜正如预期的那样表现出一定程度的细菌透过。这些实验结果已传达给客户，以便纳入其工艺验证文件中。
