Total organic carbon (TOC) and conductivity testing are important quality control measures for ensuring water purity and equipment cleanliness and can be deployed to accommodate various sampling scenarios and efficiency needs. TOC and conductivity analysis help manufacturers achieve compliance to USP <643> and USP <645>, or with process control needs. While conductivity is traditionally measured with a meter and probe, advanced TOC technologies can also offer conductivity measurements simultaneously with TOC analysis. The three common deployments of TOC technology are laboratory, at-line, and online analysis. When choosing which strategy and deployment are best for a unique application, consider the following to ensure you get the most out of the technology.
Laboratory analysis: TOC and conductivity analysis are routine tests that can be found in most Quality Control (QC) laboratories supporting cGMP operations. Benchtop TOC analyzers and software are available that allow users to stack protocols, run system protocols, run large volumes of samples at a time, manage data, and electronically sign and export data. Whether the TOC analyzer is being used for cleaning samples or water monitoring, efficiency is an important factor for most laboratories. For example, companies can now implement a “lean lab” solution that allows for simultaneous TOC and conductivity analysis from a single vial. Specialty vials are used to prevent ionic leaching from the vial surface and to prevent atmospheric CO2 from dissolving into the sample. Both of these factors can cause over-reporting of conductivity. Traditional measurement of conductivity using a meter and probe can also introduce atmospheric CO2 from having an open sample container while the measurement stabilizes. Meter and probe analysis is a very time-consuming methodology that requires analysts to test one sample at a time, wait for a stable reading, and then manually transcribe the data. Simultaneous TOC and conductivity testing ensures a lean lab and provides confidence in the data and data integrity while avoiding contamination risks. Whichever laboratory method is deployed, it is critical to have a properly calibrated and validated instrument if supporting cGMP operations. With laboratory analysis, it is inevitable that grab samples must be taken from equipment or purified water points of use. Additionally, QC laboratory workflow can take time - which is not conducive to efficient cGMP equipment turnover. With high frequency and high sample throughput, at-line or online analysis may satisfy the demand for efficiency gains in a monitoring program.
At-line analysis: At-line analysis can greatly increase process efficiency, particularly in a cleaning validation program with time constraints. At-line deployment uses a portable TOC analyzer located directly next to the process to be monitored. Once the cleaning process is complete, required samples are taken and can be analyzed almost instantaneously. This deployment is most successful for cleaning validation samples, particularly swabs, for monitoring time-critical operations. The laboratory workflow can be slow and clunky, creating unwanted equipment downtime. Coordinating activities with QC, sampling, analysis and release of data can leave equipment sitting idle for periods of time. To turn around equipment faster following cleaning, at-line analysis allows samples to be taken and immediately analyzed on a portable TOC analyzer located within reach. From there, swab and rinse sample results can be generated and reviewed within minutes, avoiding any delays from the QC workflow and reducing equipment hold times. At-line monitoring can provide efficiency gains for the right application in comparison to laboratory analysis. At-line avoids QC workflow and generates data within minutes following sample collection. For even greater efficiency, online analysis can enable real-time release of cGMP equipment and elimination of sampling activities all together. While at-line is a good fit for many applications, it limits the number of samples to be analyzed at a given time, which online analysis can overcome. Additionally, taking grab samples represents a single time point. To get multiple timepoints and a greater understanding of a process, online analysis may be the best deployment, generating multiple data points over time.
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Online analysis: A pain point of cleaning validation is equipment downtime due to the work involved in sampling and sample analysis, as mentioned above. While time constraints can be improved upon with at-line deployment, online deployment facilitates instantaneous data generation and equipment turnover. Equipment downtime can be reduced from days to minutes with real-time release using data from a TOC analyzer integrated directly onto a Clean-In-Place (CIP) skid. Programmed automation diverts CIP rinse samples from the skid directly to the analyzer for analysis. The samples are analyzed, and data are automatically exported to the site data host. Online analysis is gaining momentum for cleaning validation for efficiency and quality gains, but it has been steadfast for compendial water testing. Online TOC and conductivity testing for purified water allows for reduction or elimination of point-of-use water sampling. Online analysis makes out-of-trend results highly detectable in real time, thus allowing for preventative and corrective actions. Whether for cleaning validation or compendial water testing, it is important to consider like-for-like technology to traditional laboratory analysis when moving to online analysis. Using the same technology online as is used in established laboratory methods simplifies the method transfer process. Rather than executing a full-blown method validation, an equivalency protocol can be performed to demonstrate suitable methodology from laboratory to online using the same validated technology.
Whether deploying laboratory, at-line, or online TOC analysis, consider your goals around efficiency, analytical performance, and data integrity. Equipment that can provide high accuracy, precision, and data integrity while offering opportunities to save you time will be the most valuable to your monitoring programs. While conductivity testing is often performed in the lab with a meter and probe, advances in analytical testing now enable conductivity to be measured simultaneously with other parameters to offer greater automation. TOC and conductivity are important quality metrics to understand and control the chemical purity of purified water and cleanliness of equipment. Advances in technology now allow TOC and conductivity monitoring to be faster and more reliable than ever.
Author Biography
Michelle Neumeyer is the Life Sciences Product Applications Specialist for the Sievers line of analytical instruments at SUEZ. Previously, Michelle has worked in Quality at Novartis and AstraZeneca, ensuring compliant water systems, test methods and instrumentation. Michelle has a B.A. from University of Colorado, Boulder in Molecular, Cellular and Developmental Biology.