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 Utilities

Utilities play an important part in the production of safe and effective biologics, pharmaceuticals, and medical devices. To consistently provide products that are safe and effective, utilities must be properly designed, installed, monitored, and maintained. Utilities include, but are not limited to, electrical power; compressed air; heating, ventilation, and air conditioning (HVAC) systems; steam; gases, including medicinal; water, including potable and water for injection (WFI); vacuum; and drains. Each of these items provides its own set of unique challenges to properly support production operations and prevent contamination and cross-contamination.

The selection and design of utilities should be made on the premise of properly supporting production operations and preventing contamination and cross- contamination. Considerations should be made for the types of materials used, washing, sterilizing, and depyrogenation. Use of medical-grade materials will help minimize contamination and reduce potential biocompatibility issues.

The Pharmaceutical Inspection Convention’s Pharmaceutical Inspection Co-Operation Scheme (PIC/S) P1 009-3 details a seven-step process for pharmaceutical water systems that includes key design parameters, qualification, inspection, quality control (QC) testing, monitoring, maintenance and calibration, and documentation.

Design considerations for water used in the production of pharmaceuticals, including WFI, should use good engineering practices (GEP) using a risk-based approach that is planned and structured throughout the entire life cycle of the system. The system should consider the required water quality and its intended use, the initial water source, and storage considerations. Water shall be supplied under continuous positive pressure in a system that prevents the possibility of contamination. Additional design considerations should include weld quality, passivation, vent filters, suitability of construction materials, slope of pipe works, recirculation velocities and temperatures, check valves to prevent backflow, sanitary joints, capacity relative to demand, vales, draining and flushing, and sampling ports and locations.

Particularly important is the passivation stainless steel piping. The passivation process uses nitric or citric acid to coat the surface, thereby improving the corrosion- resistance properties by dissolving iron that has been embedded in the surface during the manufacturing process, creating a thin, transparent oxide film. When materials are not passivated, the iron can corrode and react with other materials, causing stains, discoloration, and product contamination.

Design considerations for compressed air and gas systems in the production of pharmaceuticals should use GEP with a risk-based approach that is planned and


structured throughout the entire life cycle of the system. The system should consider the required gas quality and its intended use, the initial source, and storage considerations.

Once utility systems have been designed and installed, qualification/validation should be done to ensure the system is capable. At this time, the company should determine and set operational, cleaning, sanitization, and sterilization parameters for the systems. Appropriate consideration should be given to maintenance and calibration activities.

Quality-testing methods, along with acceptable thresholds, should be developed and documented in appropriate procedures and work instructions. These procedures should document who will conduct the sampling, when samples will be taken, the minimum required sample volume, handling and storage of the samples, chemical, biological, and particulate levels, and how to handle out of specification (OOS) results. Frequent monitoring (for example, temperature, pressure, velocity), maintenance, and calibration activities should be conducted according to established procedures to ensure that the system(s) are functioning as intended.


Once utility systems have been installed, qualified, and validated, any change made to the system should be preapproved and formally documented to ensure that the system properly functions as designed. The change control process should begin with a formal facility change request (FCR). The FCR should document the scope of the proposed change, potential effect of product, materials, or processes, whether the change will require a full or partial qualification/revalidation, and maintenance and calibration activities. The approval should include signatures from appropriate departments, including operations, maintenance, and quality, before making the changes. Figure 29.1 provides a list of scenarios that may indicate revalidation



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