Susan Garcia - Senior Product Manager, Sievers Analytical Instruments, Consumables & Services
Water quality monitoring is a cornerstone of pharmaceutical production. Whether used as a raw material or for processing, formulation, reagents, intermediates, and/or cleaning, water is fundamental to GMP processes and must be monitored as such. Total organic carbon (TOC) and conductivity are two critical quality attributes that must be monitored according to USP Water for Pharmaceutical Purposes. TOC and conductivity measurements are used to demonstrate compliance to compendial regulations and to control processes, and analysis may be achieved with a variety of technologies that have a range of accuracy, precision, speed of response, and price point. Some instrumentation options, such as Sievers M9 or M500 analyzers, provide TOC and conductivity readings simultaneously, optimizing the output from the instrumentation investment.
When the decision is made to invest in new equipment, businesses can maximize the return on investment by validating the system and optimizing its use as quickly as possible. The first steps to putting a new instrument into production are installation and validation. Installation can be simple or complex depending on where the analyzer might be located (in a lab or piped into an online water loop, for example). Equipment and method validation are critical requirements for all equipment used in pharmaceutical applications to ensure functionality of the equipment and suitability for the application. Development of the validation test procedure, approval of the procedure by the Quality or Compliance group, execution of the testing, and completion of the report can consume valuable resources and can take weeks or months. Partnering with a qualified service organization that can provide the test procedure well in advance of validation test execution can expedite the validation process and minimize resource demand at the pharmaceutical company.
Once the equipment is validated and put into use, robust sampling or online monitoring processes will allow users to get the greatest benefit out of their analyzer. Certified low TOC vials are an effective way to measure TOC for point of use (POU) sampling. These vials allow samples to be collected in a clean, efficient manner and minimize external contaminants, so the TOC result is a good representation of the water source or cleaning process in question. Knowing that vials are not introducing contaminants ensures confidence in measurements and minimizes costs associated with unnecessary retests. Specialty vials are available to reduce manual or redundant processes, resulting in time and cost savings. For customers whose samples contain biologics or proteins, acidification of the sample can greatly improve recovery of the TOC in the solution, thus avoiding false low recoveries. In an application such as cleaning validation, a false low recovery (or a false sense of cleanliness) only increases risks, and ultimately costs, in the long run. Certified low TOC vials pre-treated with acid can reduce the sampling and/or processing time for these applications by eliminating the manual step of adding acid to each sample collected and ensuring consistency in the sampling and analysis process. Companies may also gain efficiencies by measuring TOC and conductivity simultaneously from a single sample, which complements a “lean lab” initiative. Specialty vials are used to prevent ionic leaching from the vial surface and to prevent CO2 from dissolving in the sample, causing over-reporting. This vial option ensures accuracy of both TOC and conductivity measurements and greatly increases sample integrity and time savings over traditional meter and probe analysis.
Every manufacturing operation must evaluate and mitigate the risk of defects or excursions. Part of the mitigation plan should include regular verification of monitoring equipment to ensure accuracy. The frequency of verification is based on many factors, including cost of undetected defects, potential scrap, production downtime, and cost and complexity of the verification process itself. Some companies choose to bracket their TOC or conductivity samples daily or weekly with known reference standards to establish a defined period or number of samples that could be subject to intervention actions in the event of monitoring system drift or failure. Reference standards used to verify equipment accuracy and precision should be certified and accredited to ISO 17034, General Requirements for the Competence of Reference Material Producers. This accreditation demonstrates the reference standards are produced in a facility with a strong quality management system that is routinely audited by an accrediting body, and the reference materials comply with international traceability and characterization requirements. Reference standards that are not certified or accredited may have higher defect rates or inaccurate uncertainties, increasing the risk of undetected process excursions.
When a water quality monitoring system failure occurs, the cost of investigation and corrective and preventive action can be extensive in both time and money. Out of specification (OOS) events frequently pull valuable resources away from business priorities and halt production or release of product until the investigation is resolved. These costs can be minimized with frequent equipment verification (minimizing product at risk) and a thorough understanding of the process equipment. As the investigation evaluates possible root causes, understanding the interaction of the components (such as the analyzer measurements, reference standards used for equipment verification, and sampling vials involved) can accelerate the speed of the investigation. Robust traceability across all the components potentially involved in the investigation can allow potential root causes to be eliminated more quickly, saving valuable time and money. Some equipment manufacturers and service providers will even partner with companies to aid in the closure of OOS investigations so end users can maximize uptime.
High quality analyzers can be extremely valuable to water processes that need to be monitored for compendial compliance and process optimization. By reducing OOS events, maximizing product output, and providing critical parameter information for water quality or cleaning process optimization, manufacturers can easily offset upfront investment. When it comes to getting the most out of instrumentation, companies are seeking accuracy, compliance, and efficiency – the combination of which enables the risk reduction and process control that lead to cost savings. However, a piece of equipment alone will not ensure that result. Equipment validation and routine performance verification provide users with peace of mind in their processes and the results obtained. Robust sampling procedures and high-quality consumables allow the analyzer to be fully utilized, and specialty vials designed for specific applications can provide additional benefits by reducing extraneous or manual processes. Pharmaceutical companies who consider the end-to-end process of water quality monitoring will be better positioned to maximize the return on analyzer investment while freeing up valuable resources to focus on top business initiatives.
Susan Garcia is the Senior Product Manager for Sievers Analytical Instruments’ consumables and services. She previously served as the Quality Engineer for Sievers consumables and as the Manufacturing Engineering Manager responsible for leading a team of engineers and technicians to support production of Sievers instruments. Susan has led significant quality improvement and product development projects during her tenure, including reference material accreditation to ISO 17025 and ISO 17034 and new consumable product launches associated with TOC and conductivity analyzers.
Susan holds a B.S. from Rice University in Chemical Engineering and has over seventeen years of experience across engineering, quality, manufacturing, and product management roles in healthcare and the life sciences. She joined GE Healthcare in 2005 and transitioned in 2010 to GE Analytical Instruments where she began her tenure with the Sievers product line.
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