The Importance of Clean Analytical Instrumentation Systems in Pharmaceutical Process Validation

by Dave Simko, Swagelok (Full-length paper presented at Interphex) Validated pharmaceutical processes are necessary to ensure quality of the products being manufactured, establish and maintain effective costs, and meet the regulatory requirements that are mandatory for approval and introduction of new pharmaceutical products. The collection of data needed to document the effectiveness and repeatability of the pharmaceutical process requires the use of a variety of both process control and analytical chemistry instrumentation. Process control instrumentation monitors process variables, such as pressure, temperature, level, and flow in a manner typical of chemical processes. The main difference in process control instrumentation for pharmaceutical processes is in the interface between the sensing element or device and the clean process stream. Analytical chemistry instrumentation monitors the chemistry of the process throughout the manufacturing process. It is especially important during the purification, compounding, and formulating of the finished product. Sample collection and conditioning—prior to introduction into the analytical instrument—is critical to reliable analysis, in both laboratory devices and in at-line and on-line analyzer systems. The cleanliness of the sampling system is an important element of reliability and repeatability. Cleanliness is impacted by the design, manufacture, and condition of the fluid control components used in the system. Consideration must be given to potential inboard, outboard, and internal leakage; effective sealing systems; entrapment; material selection; surface finishing and conditioning; and cleanability. The result of these considerations is an evaluation process that will lead to selection of the analytical chemistry instrumentation system components that will optimize repeatability and make validation easier. Component Selection Process Proper selection of components for service in clean systems is the responsibility of the system designer. Following are some elements for consideration in the selection process: Design Choose components that have proven leak-tight performance capabilities, considering potential for inboard, outboard, and internal leakage. Consider the seals used in the design. Select components with sealing systems that will meet the system’s service conditions. Look at the potential for entrapment and select components designed to minimize entrapment areas. Study the flow path through the component. Consider the component with the smoothest flow path and minimal internal volume. Consider the materials of construction and of the seal members. Be certain that they will be compatible with the pressure, temperature, and media requirements of the system. Check all ratings for compatibility with system requirements. Manufacture Check surface finishes. Components with the best surface finishes will be easier to clean and keep clean. Consider how the components are assembled and the possibilities for entrapment. Determine if the lubricants used will be compatible with the system. Cleaning Study the cleaning method used by the manufacturer and select components that will meet the system requirements initially and in service. Verification Determine what certifications will be required to verify the necessary elements of the specification or procurement document. Packaging Specify the packaging method that best meets the need of the end user.