Real-time testing results are based on the following testing (time requirements listed parenthetically):
Relying on laboratory grab samples obtained from points of use within the water system is inefficient and less reliable than using on-line TOC analyzers located at critical locations within the water distribution loop. On-line TOC analysis at a critical point in the distribution loop such as the return point in the loop prior to return into the storage tank will provide meaningful real time data and allow for collection of continuous measurements.
Grab samples are easily contaminated through the sampling process and exposure to the environment and do not always represent the “true” quality of the water generated. This however does not infer that routine monitoring of points of use should cease altogether, but rather that routine monitoring data supports the use of on-line monitoring of the chemical attributes of the water system to support real time release.
The placement and connection of the on-line TOC instrument to the water system should be based on a risk assessment. The on-line TOC measurement location shall represent the quality of the sample as measured at the points-of-use (POU). Typical placement of the instrumentation should be at a connection point in the distribution loop after the POU, before the return to the distribution storage tank, and before any purification processes on the return line. Additional on-line TOC instruments may be placed at other locations as necessary based on risk assessment.
Real-time release is supported by the Process Analytical Technology (PAT) initiative issued by the FDA. The FDA’s Process Analytical Technology (PAT) Initiative is a system for designing, analyzing and controlling manufacturing with a goal of both understanding and controlling the manufacturing process.