CONTAMINATION CONTROL - Water | Minimize Contamination Through Clean Water
By Zoe Grosser, PhD, and William Goodman
TABLE 1. Results for National Institute of Standards and Technology’s 1643e Measured with Method 200.8 for Drinking Water Trace Elements
The U.S. Food and Drug Administration (FDA) discusses eight types of water encountered in pharmaceutical processing, ranging from non-potable to sterile waters used as active ingredients in injection or irrigation.1 The U.S. Pharmacopeia (USP) general information on water for pharmaceutical use provides a flowchart outlining the steps for consideration in water purification depending upon the end use and the requirements for sterility, endotoxin tolerance, and the presence of organic materials.2 The starting material is specified as drinking water that meets the requirements of the Environmental Protection Agency (EPA, 40 CFR, part 141). What exactly does that mean for contamination remaining in the water? Are all the contaminants that might be of concern measured when drinking water is produced? We will examine the trace metals and organic compounds regulated by the EPA and discuss some of the implications for pharmaceutical manufacturing.
The most recent concern is that waste treatment plants do not completely remove low levels of pharmaceutical and personal care products and that these products may make their way into drinking water.The EPA has regulated drinking water contaminants based on health criteria since the mid-1980s. Every few years, the agency considers adding those compounds or elements with data that indicates that they may cause adverse health effects and occur in drinking water supplies. The entire list of compounds or elements regulated as primary drinking water analytes now stands at more than 90, including organic, inorganic, radioactive, and microbiological.3 The regulations generally set a maximum contaminant level (MCL), which is the highest amount of the analyte allowed in drinking water.4 The most recent concern is that waste treatment plants do not completely remove low levels of pharmaceutical and personal care products and that these products may make their way into drinking water. This is more likely to happen with surface water sources than ground water. These compounds have not been added to the regulated list at this point, and health effects at these extremely low levels have not been defined.
The EPA publishes a list of each contaminant and the allowed measurement methods. These vigorously validated methods contain a full set of quality control requirements. Other consensus methods can be considered for use, and the EPA often specifies alternative methods from Standard Methods for the Examination of Water and Wastewater or ASTM International (available at www.standardmethods.org or www.astm.org). When the ongoing update of the USP method for trace metals is complete, it will be a good method for trace metal measurement. Over the last decade, the need for productivity and rapid confirmation has increased the use of mass spectrometry measurement techniques. These methods include inductively coupled plasma mass spectrometry (ICP-MS), gas chromatography mass spectrometry (GC/MS), and liquid chromatography mass spectrometry (LC/MS).
ICP-MS Offers Efficient Analysis
Organic compounds are of concern and include compounds that can arise from pesticide and industrial chemical use. They can be measured as either volatile compounds, which can be separated from water easily by controlled heating and purging of a closed vessel, or semivolatile compounds, which are extracted from the water using solvent or solid phase extraction material and injected into the GC/MS. Mass spectrometry detection helps identify the compound with certainty. Figure 1 (below) shows an example of the type of chromatogram seen from a volatiles analysis using purge and trap GC/MS analysis with method EPA 524.2.
FIGURE 1. GC/MS chromatogram from method 524.2 showing a calibration standard. Each peak represents an individual organic compound. Very few peaks are found in finished drinking water.
More than 60 trace metals and specific organic compounds are measured on a regular basis to ensure that drinking water is safe for even the most sensitive populations. Methodology developed for these measurements incorporates a sophisticated level of quality control to help ensure accurate and precise measurements. Further purification and testing may be done for pharmaceutical manufacturing use, but the basic starting material is fairly well characterized.
Current issues of interest that may influence the testing done prior to use is the possible presence of pharmaceuticals and personal care products at extremely low concentrations. These can be measured using currently available technology, but the health effects of chronic exposure to low levels of these materials has not been defined, and they are, therefore, not regulated. In the case of inorganic analytes, several different elements are included in new USP methodology for excipient and active ingredient analysis. If desired, they can be included in the analytical protocol for the incoming material, and a more thorough evaluation of the water can be made before further purification.
More than 60 trace metals and specific organic compounds are measured on a regular basis to ensure that drinking water is safe for even the most sensitive populations.
- U.S. Food and Drug Administration. Inspection technical guide: water for pharmaceutical use. FDA. Available at: www.fda.gov/ICECI/Inspections/InspectionGuides/InspectionTechnicalGuides/ucm072925.htm. Accessed December 10, 2010.
- U.S. Pharmacopeia. General information chapter 1231: water for pharmaceutical use. USP. Available at: http://pharmacopeia.cn/v29240/usp29nf24s0_c1231.html. Accessed December 10, 2010.
- U.S. Environmental Protection Agency. Contaminants regulated under the safe drinking water act. EPA. Available at: http://water.epa.gov/drink/contaminants/upload/2003_05_27_contaminants_contam_timeline.pdf. Accessed December 10, 2010.
- U.S. Environmental Protection Agency. Drinking water contaminants: list of contaminants and their MCLs. EPA. Available at: http://water.epa.gov/drink/contaminants/index.cfm#List. Accessed December 10, 2010.
- Mahar M, Neubauer K, Grosser Z. Improved performance in the analysis of drinking waters and wastewaters by U.S. EPA Method 200.8 with an SC-FAST system. Application Note 008278_01. PerkinElmer, Inc. 2008. Available at: www.perkinelmer.com/search/Search.aspx?Ntt=SC-FAST&N=16&within=&previousText=SC-FAST&CName=Application%20Notes. Accessed December 10, 2010.