Dear Fresh Water Systems,
Regarding pharmaceutical grades of water, purified water can be made using any suitable method. However, it must pass the USP shelf-life standards which are detailed in the folowing tables. It is the maintainence of the water production system that is of concern to those in water treatment.
Purified Water is to be used in the production or compounding of USP products. Manufacturing is controlled by the FDA ,while compounding is controlled at the state level by the boards of pharmacy.
FB – Scientific Staff, United States Pharmacopeia
USP Standards for Packaged Purified Water, Water for Injection and Sterile Purified Water (USP24 effective 1/1/00)
The following are numerical value limits that are commonly used interpretations* of the procedures listed on pages 1752 and 1753 under the individual monographs:
The following are numerical value limits that are commonly used interpretations* of the procedures listed on pages 1752 and 1753 under the individual monographs:
| pH | 5.0 to 7.0 |
| Chloride (mg/l) | 0.5 |
| Sulfate (mg/l) | 1.0 |
| Ammonia (mg/l) | 0.03 |
| Calcium (mg/l) | 1.0 |
| Carbon Dioxide (mg/l) | 5.0 |
| Oxidizable Substances | Pass the USP Permanganate test |
| Bacteria | Purified Water (CFU/ml) 100
WFI (CFU/100ml) 10
Sterile PW — Pass the USP Sterility test <71>
|
| Endotoxin WFI (EU/ml) | 0.25 |
Note: The actual USP tests are colorimetric tests and the USP24 must be consulted for the procedures. USP24 may be found at the libraries of pharmacy and medical schools and some reference libraries. It may also be purchased by calling 800-822-8772. TOC and Conductivity testing is not approved for packaged water because of interferences from materials extracted from the plastic or glass containers. Purified Water and Sterile Purified Water may be “obtained by any suitable process”. Water for Injection is “water purified by distillation or reverse osmosis”. Regulatory agencies have required that packaged PW and WFI be tested by the producer using TOC and conductivity prior to packaging. It is advisable that the purchaser obtain this assurance.
Source: The PhRMA Water Quality Group
These limits are Guidelines found in General Chapter <1231>
The “wet” chemistry tests and the oxidizable substance test in the USP23 monographs for PW and WFI were deleted. They were replaced with a Water Conductivity test for ionic impurities and a Total Organic Carbon test (TOC) for organic impurities.
The current standards for PW and WFI are:
TOC – 500 ppb Carbon
Conductivity – 1.3 TS / cm @ 25°
1.1 TS / cm @ 20°
Bacteria – PW-100 cfu/mL
(guidelines in <1231>) WFI-10 cfu/100mL
Bacterial Endotoxins – WFI-0.25 USP Eu/mL
USP24 contains complete versions of all pharmaceutical water monographs p. 1752-1754 and the general chapters <643> TOC, <645> Water Conductivity p. 1927-1929, and <1231> Water for Pharmaceutical Purposes p. 2154-2163. You may purchase USP24 by calling Customer Service at (800) 877-6733. We can not provide photocopies of copyrighted material. The USP is also available at pharmacy colleges, medical colleges, pharmaceutical manufacturers, equipment manufacturers, and some reference libraries.
You are advised that the TOC limit of 500 ppb C is the “target” limit response. The actual number can vary based upon your equipment, the sucrose reference solution prepared, background carbon etc. Also, accurate offline TOC testing requires a high level of vigilance to avoid contamination during sampling and testing. The frequency of system suitability testing is a program decision, taking into account your current Q.C. practice and your regulatory risk. The Conductivity Test meter and the conductivity cell must both be calibrated as per <645> and the use of a non-temperature-compensated meter is required specifically in Stage 1 testing.
The monographs for all packaged pharmaceutical waters continue to require “wet” chemistry tests and the Oxidizable Substance test because of possible contamination from the packaging material used, which can influence test results. (See the Sterile Purified Water monograph). The manufacture of PW & WFI has not changed. Purified Water may be produced by any suitable process. WFI must be produced by distillation or reverse osmosis only.
TOC reference standards may be purchased by calling the same general USP number. Only USP reference standards have been tested and approved as suitable for use in USP tests and assays.
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