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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:
  1. Excess levels of aluminum, fluorides, and chlorides may be found seasonally in drinking water as a result of chemicals used in water treatment. These components should be monitored in Water for Hemodialysis being produced in accordance with established standard operating procedures. The maximum acceptable levels of these elements and compounds are listed in Table 1.
  2. A comprehensive validation testing of the system producing Water for Hemodialysis should be performed, at least annually, to ensure that the water treatment equipment is functioning properly. The maximum acceptable levels of elements and compounds are listed in Table 1. Routine testing is performed in accordance with the monograph.
Table 1. Maximum Allowable Chemical Levels in Water
for Hemodialysis (water used to prepare dialysate and con-
centrates from powder at a dialysis facility and to
reprocess dialyzers for multiple use)*
Element or Compound Maximum Concentration
Calcium 2 (0.1 mEq/L)
Magnesium 4 (0.3 mEq/L)
Potassium 8 (0.2 mEq/L)
Sodium 70 (3.0 mEq/L)
Antimony 0.006
Arsenic 0.005
Barium 0.10
Beryllium 0.0004
Cadmium 0.001
Chromium 0.014
Lead 0.005
Mercury 0.0002
Selenium 0.09
Silver 0.005
Aluminum 0.01
Chloramines 0.10
Free chlorine 0.50
Copper 0.10
Fluoride 0.20
Nitrate (as N) 2.00
Sulfate 100.00
Thallium 0.002
Zinc 0.10
*  Reprinted with permission from ANSI/AAMI RD62: 2001, Water treatment equipment for hemodialysis applications, copyright Association for the Advancement of Medical Instrumentation, Arlington, VA.
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 action taken.
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, 19th 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 described in ANSI/AAMI RD 62:2001.

The Water for Hemodialysis monograph includes microbial limits of 100 cfu per mL and endotoxin limits of 2 USP Endotoxin Units per mL. Culture media should be tryptic soy agar or equivalent, and colonies should be counted after incubation at a temperature range between 30 and 35, for no less than 48 hours. Sampling the water should be done at the end of the water purification cascade at the point 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. Quantification of bacterial endotoxins is performed using the Limulus Amebocyte Lysate (LAL) clotting method or any other LAL test 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 recommended Action Level for a total viable microbial count in the product water is 50 cfu per mL, and the recommended Alert Level for bacterial endotoxins is 0.5 USP Endotoxin Unit per mL (also see Microbial Considerations under Water for Pharmaceutical Purposes 1231).

1  American Public Health Association, Washington, DC 20005.
2  U.S. Environmental Protection Agency Publication EPA-600-R-94-111, Cincinnati, OH.

Auxiliary Information—
Staff Liaison : Gary E. Ritchie, M.Sc., Scientific Fellow
Expert Committee : (PW05) Pharmaceutical Waters 05
USP29–NF24 Page 3055
Pharmacopeial Forum : Volume No. 31(5) Page 1486
Phone Number : 1-301-816-8353