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ITG SUBJECT: MEASUREMENT OF RELATIVE HUMIDITY IN THE EO PROCESS The importance and criticality of the moisture content or relative humidity (RH) of the environment within the enclosed vessel of the Ethylene Oxide (EO) sterilization process has been well established by the drug and device industries. Appropriate instrumentation systems are necessary to sense, control, and record this parameter. Of these, the key element of the system and the most difficult to establish and maintain in terms of accuracy is the moisture sensor. This ITG will briefly describe basic types of sensors together with some limitations. TYPES OF SENSORS/INSTRUMENTS The simplest form of RH measurement and one with which most are familiar, is the traditional Mechanical Hygrometer. It is based on the principle that certain materials will expand or contract as a function of the amount of moisture absorbed. Materials such as paper, wood, bone, plant leaves, textiles, animal tissue and plastics have been historically used. The most common materials, however, have been human or horse hair. Direct readout is usually obtained on a dial indicator interconnected to the material via mechanical linkage. It is also obvious that such an instrument would be difficult for remote reading in the enclosed space of a sterilization chamber and for all practically could not be used. It is also obvious that precision would not be a relied-upon quality. Response is slow for both increasing and decreasing humidity and temperature compensation cannot be made (calibration applies only to a specific temperature). Also, the aging process of the material is not uniform, making calibration extremely difficult. It is doubtful that the investigator will ever encounter the use of such an instrument to measure the RH in an EO chamber. Electric Hygrometer - This type utilizes a sensor that is a hygroscopic film. An instantaneous change of electrical resistance or capacitance can be measured as the result of small changes in absorbed moisture by the film. The hygroscopic film is sometimes replaced by a wire grid wrapped around a substrate. The wire grid is usually coated with a hygroscopic salt solution (lithium chloride is common) which absorbs water vapor. Resistance of the wire grid corresponds to a calibrated RH value. A calibration curve is usually furnished for each unit by the manufacturer. In physical appearance for EO chamber use, the sensor most likely will resemble a metallic or plastic cylinder approximately 3/4 inch diameter by 2 inch long with perforations on the side and electrical contact pins or connector on an end. The response to changing RH is rapid and accuracy tolerances can be as low as ± 1.5% RH. This type of sensor usually is not reliable after multiple exposures to EO. A maintenance program to clean, rejuvenate, and recalibrate periodically is necessary for the user. The investigator should also be alerted to the fact that humidity sensitive materials are also temperature dependent. This means that the sensor must be calibrated over the entire temperature range of operation. Dew-Point Hygrometer - This is commonly known as the chilled mirror technique wherein the optical qualities of a mirror are measured as it is cooled by the sampled gas to cause condensation. The amount of condensation is related to the dew-point temperature which together with a dry bulb temperature and a standard chart can be interpolated to reveal RH. This method can be quite accurate (± 2% RH). One manufacturer utilizes microprocessor technology to offer simultaneous measurement of not only dew-point but temperature and RH as well, with a digital readout display. Accuracy in determining RH has been claimed as low as ± 0.5%. Maintenance required for this type of sensor would be primarily the cleaning of the mirror and sampled gas line. Gas Liquid Chromatography (GLC) - This technique utilizes sampling of the gas mixtures in the contained vessel. The areas under the curves generated by the GLC are measured manually or automatically with a microprocessor to determine concentrations of sterilant gases, air, and moisture contents (RH). This is probably the most accurate means to measure RH. The critical factor is proper maintenance of the instrument and periodic calibration. The sampling ports must be clear and free of any debris and the sampling lines must be heated and insulated to prevent condensation. Not everyone understands the principles of GC; therefore, a qualified person, usually a chemist should be responsible for adjustments or maintenance of the equipment. This method also lends itself quite well to process control systems. CONCLUSION Other forms of sensors and instruments are available for measuring RH. Most are variations of the basic types described but they offer much less in practicality for the EO sterilizer. Some firms choose to use an empirical method for determining RH. Based upon the laws of thermodynamics for an ideal gas, RH, which is a ratio, can be expressed as a percentage of the mole fraction of water vapor in a space (chamber) to the mole fraction of water vapor in the space at saturation at a particular temperature. In the case of the EO chamber, this could be expressed in pressures for practical engineering applications by the equation: % RH =/_\ P (Change in absolute pressure) psia x 100
------
P sv (Saturation vapor pressure) psia
Where,/_\ P is the change in absolute pressure of the chamber resulting from steam injection after the pre-evacuation portion of the cycle and P sv is the saturation vapor pressure taken from published tables of saturated steam and temperature. (See the attached excerpt of such a table). As an example, steam is injected into the EO chamber to increase the pressure by 3.0 in. Hg. (1.47 psia). Sterilization temperature is 130 F and from the attached table of saturation vapor pressure at a temperature, P sv = 2.2230 psia. The equation then becomes: RH = 1.47
-------- x 100 = 66%
2.2230
The use of the empirical method is adequate providing that all instrumentation to measure both pressures and temperature are adequately calibrated and maintained. Validation/qualification of the process should verify the accuracy of the calculations. Some firms utilize this method as a means for back-up or for cross-checking to determine faulty sensors. The investigator is invited to also utilize this method for a rapid check of the RH parameter of the EO process during the Establishment Inspection. References
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i Attachment to ITG #47
_____________________
Saturated Steam: Temperature Table
Chamber
Temp. Psv
___________________________________________________________________________________________________________________________________
Abs Press. Specific Volume Enthalpy Entropy
Temp Lb per Sat. Sat. Sat. Sat. Sat. Sat. Temp
Fahr Sq In. Liquid Evap Vapor Liquid Evap Vapor Liquid Evap Vapor Fahr
t p v f v fg v g h f h fg h g S f S fg S g t
___________________________________________________________________________________________________________________________________
32.0* 0.08859 0.016022 3304.7 3304.7 -0.0179 1075.5 1075.5 0.0000 2.1873 2.1873 32.0*
34.0 0.09600 0.016021 3061.9 3061.9 1.996 1074.4 1076.4 0.0041 2.1762 2.1802 34.0
36.0 0.10395 0.016020 2839.0 2839.0 4.008 1073.2 1077.2 0.0081 2.1651 2.1732 36.0
38.0 0.11249 0.016019 2634.1 2634.2 6.018 1072.1 1078.1 0.0122 2.1541 2.1663 38.0
40.0 0.12163 0.016019 2445.8 2445.8 8.027 1071.0 1079.0 0.0162 2.1432 2.1594 40.0
42.0 0.13143 0.016019 2272.4 2272.4 10.035 1069.8 1079.9 0.0202 2.1325 2.1527 42.0
44.0 0.14192 0.016019 2112.8 2112.8 12.041 1068.7 1080.7 0.0242 2.1217 2.1459 44.0
46.0 0.15314 0.016020 1965.7 1965.7 14.047 1067.6 1081.6 0.0282 2.1111 2.1393 46.0
48.0 0.16514 0.016021 1830.0 1830.0 16.051 1066.4 1082.5 0.0321 2.1006 2.1327 48.0
50.0 0.17796 0.016023 1704.8 1704.8 18.054 1065.3 1083.4 0.0361 2.0901 2.1262 50.0
52.0 0.19165 0.016024 1589.2 1589.2 20.057 1064.2 1084.2 0.0400 2.0798 2.1197 52.0
54.0 0.20625 0.016026 1482.4 1482.4 22.058 1063.1 1085.1 0.0439 2.0695 2.1134 54.0
56.0 0.22183 0.016028 1383.6 1383.6 24.059 1061.9 1086.0 0.0478 2.0593 2.1070 56.0
58.0 0.23843 0.016031 1292.2 1292.2 26.060 1060.8 1086.9 0.0516 2.0491 2.1008 58.0
60.0 0.25611 0.016033 1207.6 1207.6 28.060 1059.7 1087.7 0.0555 2.0391 2.0946 60.0
62.0 0.27494 0.016036 1129.2 1129.2 30.059 1058.5 1088.6 0.0593 2.0291 2.0885 62.0
64.0 0.29497 0.016039 1056.5 1056.5 32.058 1057.4 1089.5 0.0632 2.0192 2.0824 64.0
66.0 0.31626 0.016043 989.0 989.1 34.056 1056.3 1090.4 0.0670 2.0094 2.0764 66.0
68.0 0.33889 0.016046 926.5 926.5 36.054 1055.2 1091.2 0.0708 1.9996 2.0704 68.0
70.0 0.36292 0.016050 868.3 868.4 38.052 1054.0 1092.1 0.0745 1.9900 2.0645 70.0
72.0 0.38844 0.016054 814.3 814.3 40.049 1052.9 1093.0 0.0783 1.9804 2.0587 72.0
74.0 0.41550 0.016058 764.1 764.1 42.046 1051.8 1093.8 0.0821 1.9708 2.0529 74.0
76.0 0.44420 0.016063 717.4 717.4 44.043 1050.7 1094.7 0.0858 1.9614 2.0472 76.0
78.0 0.47461 0.016067 673.8 673.9 46.040 1049.5 1095.6 0.0895 1.9520 2.0415 78.0
80.0 0.50683 0.016072 633.3 633.3 48.037 1048.4 1096.4 0.0932 1.9426 2.0959 80.0
82.0 0.54093 0.016077 595.5 595.5 50.033 1047.3 1097.3 0.0969 1.9334 2.0303 82.0
84.0 0.57702 0.016082 560.3 560.3 52.029 1046.1 1098.2 0.1006 1.9242 2.0248 84.0
86.0 0.61518 0.016087 227.5 527.5 54.026 1045.0 1099.0 0.1043 1.9151 2.0193 86.0
88.0 0.65551 0.016093 496.8 496.8 56.022 1043.9 1099.9 0.1079 1.9060 2.0139 88.0
90.0 0.69813 0.016099 468.1 468.1 58.018 1042.7 1100.8 0.1115 1.8970 2.0086 90.0
92.0 0.74313 0.016105 441.3 441.3 60.014 1041.6 1101.6 0.1152 1.8881 2.0033 92.0
94.0 0.79062 0.016111 416.3 416.3 62.010 1040.5 1102.5 0.1188 1.8792 1.9980 94.0
96.0 0.84072 0.016117 392.8 392.9 64.006 1039.3 1103.3 0.1224 1.8704 1.9928 96.0
98.0 0.89356 0.016123 370.9 370.9 66.003 1038.2 1104.2 0.1260 1.8617 1.9876 98.0
100.0 0.94924 0.016130 350.4 350.4 67.999 1037.1 1105.1 0.1295 1.8530 1.9825 100.0
102.0 1.00789 0.016137 331.1 331.1 69.995 1035.9 1105.9 0.1331 1.8444 1.9775 102.0
104.0 1.06965 0.016144 313.1 313.1 71.992 1034.8 1106.8 0.1366 1.8358 1.9725 104.0
106.0 1.1347 0.016151 296.16 296.18 73.99 1033.6 1107.6 0.1402 1.8273 1.9675 106.0
108.0 1.2030 0.016158 280.28 280.30 75.98 1032.5 1108.5 0.1437 1.8188 1.9626 108.0
110.0 1.2750 0.016165 265.37 265.39 77.98 1031.4 1109.3 0.1472 1.8105 1.9577 110.0
112.0 1.3505 0.016173 251.37 251.38 79.98 1030.2 1110.2 0.1507 1.8021 1.9528 112.0
114.0 1.4299 0.016180 238.21 238.22 81.97 1029.1 1111.0 0.1542 1.7938 1.9480 114.0
116.0 1.5133 0.016188 225.84 225.85 83.97 1027.9 1111.9 0.1577 1.7856 1.9433 116.0
118.0 1.6009 0.016196 214.20 214.21 85.97 1026.8 1112.7 0.1611 1.7774 1.9386 118.0
120.0 1.6927 0.016204 203.25 203.26 87.97 1025.6 1113.6 0.1646 1.7693 1.9339 120.0
122.0 1.7891 0.016213 192.94 192.95 89.96 1024.5 1114.4 0.1680 1.7613 1.9293 122.0
124.0 1.8901 0.016221 183.23 183.24 91.96 1023.3 1115.3 0.1715 1.7533 1.9247 124.0
126.0 1.9959 0.016229 174.08 174.09 93.96 1022.2 1116.1 0.1749 1.7453 1.9202 126.0
128.0 2.1068 0.016238 165.45 165.47 95.96 1021.0 1117.0 0.1783 1.7374 1.9157 128.0
130.0 2.2230 0.016247 157.32 157.33 97.96 1019.8 1117.8 0.1817 1.7295 1.9112 130.0
132.0 2.3445 0.016256 149.64 149.66 99.95 1018.7 1118.6 0.1851 1.7217 1.9068 132.0
134.0 2.4717 0.016265 142.40 142.41 101.95 1017.5 1119.5 0.1884 1.7140 1.9024 134.0
136.0 2.6047 0.016274 135.55 135.57 103.95 1016.4 1120.3 0.1918 1.7063 1.8980 136.0
138.0 2.7438 0.016284 129.09 129.11 105.95 1015.2 1121.1 0.1951 1.6986 1.8937 138.0
140.0 2.8892 0.016293 122.98 123.00 107.95 1014.0 1122.0 0.1985 1.6910 1.8895 140.0
142.0 3.0411 0.016303 117.21 117.22 109.95 1012.9 1122.8 0.2018 1.6534 1.8852 142.0
144.0 3.1997 0.016312 111.74 111.76 111.95 1011.7 1123.6 0.2051 1.6759 1.8810 144.0
146.0 3.3653 0.016322 106.58 106.59 113.95 1010.5 1124.5 0.2084 1.6684 1.8769 146.0
148.0 3.5381 0.016332 101.68 101.70 115.95 1009.3 1125.3 0.2117 1.6610 1.8727 148.0
150.0 3.7184 0.016343 97.05 97.07 117.95 1008.2 1126.1 0.2150 1.6536 1.8686 150.0
152.0 3.9065 0.016353 92.66 92.68 119.95 1007.0 1126.9 0.2183 1.6463 1.8646 152.0
154.0 4.1025 0.016363 88.50 88.52 121.95 1005.8 1127.7 0.2216 1.6390 1.8606 154.0
156.0 4.3068 0.016374 84.56 84.57 123.95 1004.6 1128.6 0.2248 1.6318 1.8566 156.0
158.0 4.5197 0.016384 80.82 80.83 125.96 1003.4 1129.4 0.2281 1.6245 1.8526 158.0
160.0 4.7414 0.016395 77.27 77.29 127.96 1002.2 1130.2 0.2313 1.6174 1.8487 160.0
162.0 4.9722 0.016406 73.90 73.92 129.96 1001.0 1131.0 0.2345 1.6103 1.8448 162.0
164.0 5.2124 0.016417 70.70 70.72 131.96 999.8 1131.8 0.2377 1.6032 1.8409 164.0
166.0 5.4623 0.016428 67.67 67.68 133.97 998.6 1132.6 0.2409 1.5961 1.8371 166.0
168.0 5.7223 0.016440 64.78 64.80 135.97 997.4 1133.4 0.2441 1.5892 1.8333 168.0
170.0 5.9926 0.016451 62.04 62.06 137.97 996.2 1134.2 0.2473 1.5822 1.8295 170.0
172.0 6.2736 0.016463 59.43 59.45 139.98 995.0 1135.0 0.2505 1.5753 1.8258 172.0
174.0 6.5656 0.016474 56.95 56.97 141.98 993.8 1135.8 0.2537 1.5684 1.8221 174.0
176.0 6.8690 0.016486 54.59 54.61 143.99 992.6 1136.6 0.2568 1.5616 1.8184 176.0
178.0 7.1840 0.016498 52.35 52.36 145.99 991.4 1137.4 0.2600 1.5548 1.8147 178.0
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