1230 WATER FOR HEMODIALYSIS APPLICATIONS
GENERAL PURIFICATION CONSIDERATIONS
Chemical and microbial components that can be found in drinking water meeting U.S. Environmental Protection Agency National Primary Drinking Water Regulations (or equivalent) may have the potential to produce significant negative effects in patients undergoing hemodialysis. It is, therefore, necessary to subject the water to further treatment to reduce these components to acceptable levels. The Water for Hemodialysis monograph provides bacterial and chemical tests that are required to ensure patient safety. Additional testing is recommended as follows:
Table 1. Maximum Allowable Chemical Levels in Water for Hemodialysis
(water used to prepare dialysate and concentrates from powder at a dialysis facility and to reprocess dialyzers for multiple use)*
The chemical limits included in Table 1 have been recognized by federal government agencies as standards for Water for Hemodialysis. Written standard operating procedures for water testing should be established by the physician in charge or the designated facility manager. The test frequency decision should be based upon historical data analysis, the quality of the source water as reported by the municipal water treatment facility or public health agency in the area, etc. Records should be maintained to document levels and any necessary remedial action taken promptly.
Chemical analysis of water components listed should be performed using methods referenced in the American Public Health Association's Standard Methods for the Examination of Water and Wastewater, 21st Edition,1 those referenced in the U.S. Environmental Protection Agency's Methods for the Determination of Metals in Environmental Samples,2 or equivalent methods as referenced in ANSI/AAMI RD 62:2006.
The Water for Hemodialysis monograph includes total aerobic microbial count (TAMC) limits of 100 cfu/mL and endotoxin limits of 1 USP Endotoxin Unit/mL. In addition, the absence of Pseudomonas aeruginosa should be routinely determined because this is an opportunistic pathogen hazardous to acutely ill hemodialysis patients. Both the high microbial counts and the presence of Pseudomonas aeruginosa can be associated with inadequate water system maintenance and sanitization. Sampling the water should be done at all use points where the water enters the dialysis equipment. Samples should be assayed within 30 minutes of collection or immediately refrigerated and then assayed within 24 hours of collection. The microbial enumeration and absence tests are performed using procedures found in the USP general test chapters Microbial Enumeration Tests 61 and Tests for Specified Microorganisms 62. Quantification of bacterial endotoxins is performed using procedures found in the USP general test chapter Bacterial Endotoxins Test 85.
Because of the incubation time required to obtain definitive microbiological results, water systems should be microbiologically monitored to confirm that they continue to produce water of acceptable quality. Alert and Action Levels are therefore necessary for the monitoring and control of the system. An Alert Level constitutes a warning and does not require a corrective action. An Action Level indicates a drift from normal operating conditions and requires that corrective action be taken to bring the process back into the normal operating range. Exceeding an Alert or Action Level does not imply that water quality has been compromised. The maximum recommended Action Level for a total viable microbial count in the product water should be no greater than 25 cfu/mL, and the maximum recommended Action Level for bacterial endotoxins should be no greater than 0.25 USP Endotoxin Unit/mL. As with all process control values, Action and Alert Levels should be established from normal system monitoring trends and process capabilities in a fashion that allows remedial actions to occur in response to process control level excursions well before specifications are exceeded (also see Microbial Considerations under Water for Pharmaceutical Purposes 1231).
1 American Public Health Association, Washington, DC 20005.
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USP35NF30 Page 885Pharmacopeial Forum: Volume No. 35(6) Page 1531