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18 Pharmaceutical Technology BIOLOGICS AND STERILE DRUG MANUFACTURING 2020 P h a r mTe c h . c o m Manufacturing It is possible to instrument a single-use system (SUS) using completely traditional instruments. However, there are several challenges with incorporating any sensors and associated fittings into a SUS, as these instruments must: • Withstand initial sterilization, usually using gamma radiation • Interact with process media contained within the bioreactor bag, either using direct contact or via a membrane • Include provisions for initial calibration or zeroing • Often need to be calibrated during a produc- tion run • Be reusable, if possible, and withstand removal at the end of a production run and re-installation at the beginning of the next run. Specific single-use sensors and fittings are designed and built to address each of these issues, so end users can safely and reliably operate their equipment. Making the connection There are two types of connection for any single-use sensor: electrical and physical. The electrical connec- tion to an associated transmitter is external to the equipment and can therefore use the same form fac- tors as traditional devices. The sensor and transmitter combination is referred to as an instrument. The physical connection to the process is much more problematic. These connectors may also be called fittings, ports, or adapters, and they must be manufactured into the single-use bag itself to mate to the instrument or sensor while maintaining aseptic conditions. These fittings are mechanically designed to avoid compromising the bag integrity with any type of leakage or contamination. Fitting materials must meet high biocompatibility standards, so they are typically tested to ensure com- pliance with United States Pharmacopeia Class VI standards, with clean natural profiles and no animal- derived ingredients. Because single-use bags are steril- ized using gamma radiation, the fitting materials also need to be suitable for this type of treatment. Addi- tional extractables and leachables testing must verify that fitting materials will not degrade during steril- ization or production. Compliance can be difficult to achieve and expensive to confirm. Single-use measurement examples Each measurement type usually requires a matched fit- ting design. The next sections discuss specific sensors and fittings for various measurements. Pressure sensing. Pressure measurement sensors are commonly employed, but the actual sensor or a dia- phragm connected via a capillary tube must typi- cally contact the process media. Traditional sensors in biopharmaceutical use must be specified for the operating and sterilization conditions. Often, a trans- mitter is incorporated with the sensor to convert the low-level signal to a common industrial signal range. For single-use processing, proven pressure sen- sor technology must be adapted into a size profile suitable for single-use connectors. The sensors should deliver an accuracy of +/- 0.15 psi so they can be used for precise control and safety applica- tions. Once calibrated, the ability to zero the in- strument in place and deliver long-term stability helps users quickly start up batches with minimal downtime, while reducing the need for a spare parts inventory. A 4–20-mA transmitter output is industry-standard and compatible with any indus- trial control system. The key to pressure measurement for single-use is using a specific instrument with a matching process connector, such as shown in Figure 1. In this example,