An overview of the validation approach for moist heat_part I(3)

Table I: Temperature data interpretation for a heat distribution study during exposure phase.Function Minimum temperature Run Number 1 2 3 4 1 2 3 4 1 2 3 4 T5 120.43 121.71 121.35 121.85 123.27 121.91 122.37 122.16 121.76 121.84 121.88 122.00 121.87 0.10 T0 121.87 121.81 121.91 122.09 122.02 122.13 122.22 122.44 121.95 121.97 122.05 122.21 122.05 0.12 Values within the Run Thermocouple Numbers for Heat Distribution T1 T2 T3 T4 T6 121.85 121.37 121.79 121.71 121.53 121.82 121.77 121.92 121.81 121.39 121.92 121.84 121.75 121.71 121.53 122.07 122.01 122.02 122.10 121.66 122.02 121.96 122.16 122.14 121.92 122.02 121.98 122.15 122.20 122.02 122.14 122.08 122.30 123.45 122.00 122.42 122.34 122.35 122.46 122.16 121.93 121.87 121.99 121.98 121.73 121.94 121.89 122.06 122.02 121.72 122.03 121.96 122.15 122.18 121.77 122.19 122.11 122.12 122.22 121.89 122.02 121.96 122.09 122.10 121.84 0.12 0.11 0.06 0.11 0.12 T7 121.62 121.58 121.62 121.29 122.05 122.07 122.12 122.83 121.82 121.85 121.85 121.94 121.84 0.08 T8 121.63 121.78 121.70 121.83 122.03 122.25 122.16 122.39 121.81 122.03 121.93 122.01 121.95 0.09 Values across the Run 120.43 121.39 121.35 121.28 123.27 122.24 123.44 122.82 121.89 121.92 121.98 122.08

Maximum temperature

Mean temperature

Mean of the four runs Standard deviation for the means t value

1 2 3 4 1 2 3 4

—

0.07

0.10

0.28

0.01

0.02

0.71

0.69

0.30

0.09 0.10 0.13 0.12— 0.59 0.15 0.002

One thermocouple must always be located next to the autoclave temperature probe, which is usually placed in the chamber drain. The reason for this practice is that, theoretically

, the“cold spot” of a chamber is in the drain. Depending on various chambers’ geometry, sometimes the location of the cold spot in the chamber drain is not confirmed in practice. The OQ phase consists of a verification of the equipment functionality. A series of checks and tests should be performed after the unit is installed. The proper operation of alarms and safety devices also must be tested. For a prevacuum cycle involving an air-removal phase, the attainability, effectiveness, and consistency in time of vacuum conditions must be tested. Chamber mapping consists of heat distribution studies throughout the chamber for each sterilizing temperature used. Heat distribution studies determine during processing whether the temperature is uniform and reproducible throughout the empty chamber and localize the cold spots within the chamber. These studies also confirm that the system works within the specified limits throughout the entire range of operational parameters. The sterilizing temperatures are programmed into the autoclave controls. For each sterilizing temperature being validated, the empty chamber should be monitored three times during a period of one hour, and the reproducibility of the results obtained must be compared. The comparative readings of the reference temperature sensor, the thermocouple near the temperature sensor, and the temperature displayed by the autoclave recorder should be 1 C. During the exposure phase, a difference no greater than 2.5 C between the temperature of100

the chamber’s coolest spot and the mean chamber temperature is acceptable (8). Performance qualification (PQ) phase. PQ represents the confirmatory phase of the validation program and consists of tests performed with the autoclave chamber under loaded conditions. During the PQ phase, which is sometimes referred to as process validation, the following objectives must be attained (1):● demonstration of the uniformity and effectiveness of the process in inactivating or removing microorganisms to the required safety level● demonstration of the reproducibility of the process—through the use of sufficient cycles● demonstration of the compatibility of the process with the items to be sterilized—through the assessment of the influence of the sterilization process on the products. The PQ phase consists of studies that use thermocouples inserted into the articles being sterilized and studies that use BIs in operationally fully loaded autoclave conditions (2). Heat penetration studies are considered the most critical component of the entire validation program. These studies are intended to find areas in the loads that are difficult to penetrate or heat. When selecting the monitoring sites, one must take into account the cold spots previously found during the monitoring of the empty chamber. Heat penetration studies must demonstrate the reproducibility of a cycle in relation to the loads and the effectiveness of the killing effect throug

hout the chamber and load. Selecting loading configurations must be performed very carefully and should be based on worst-case situations. The maxiwww.phar

Pharmaceutical Technology

OCTOBER 2002

Table II: Temperature data interpretation for a heat penetration study during exposure phase.Function Minimum temperature Run Number T10 1 120.26 2 120.84 3 120.62 4 120.81 1 123.10 2 122.35 3 122.83 4 122.91 1 121.67 2 121.53 3 121.63 4 121.58 121.60 1 2 3 4 1 2 3 4 0.06 T11 120.91 121.35 120.95 121.48 122.33 121.92 122.27 122.14 121.68 121.63 121.62 121.77 121.67 0.06 Values within the Run Thermocouple Numbers for Heat Penetration T12 T13 T14 T15 T16 T17 121.05 120.76 120.69 120.86 120.57 120.67 121.04 120.80 121.08 120.73 120.80 120.87 121.18 120.96 120.86 120.92 120.45 121.15 121.31 121.33 121.19 121.38 121.27 121.20 122.20 122.31 122.66 122.34 122.49 122.52 122.11 122.31 121.99 122.40 122.10 122.17 122.01 122.04 121.91 122.09 121.85 121.71 122.26 122.19 122.32 122.20 122.37 122.27 121.69 121.61 121.64 121.60 121.53 121.55 121.55 121.53 121.56 121.57 121.56 121.63 121.54 121.53 121.45 121.54 121.33 121.52 121.81 121.81 121.84 121.83 121.82 121.84 121.64 121.62 121.62 121.63 121.56 121.63 0.12 0.13 1.66 0.13 0.2 0.14 T18 120.91 121.07 120.22 121.14 122.28 122.04 122.40 122 …… 此处隐藏：21968字，全部文档内容请下载后查看。喜欢就下载吧 ……