Why wet storage is key for biopharmaceutical single-use pH sensor performance

For biopharmaceutical single-use applications, pH sensors designed for wet storage deliver needed long shelf life and one-point calibration.

Brandon Haschke, Emerson

Biopharmaceutical processing applications, and especially single-use technology (SUT) manufacturing methods, present unique challenges for performing pH measurements. Quite often these processes are automated, and certainly they all must be monitored, so there is always a need to sense the process media pH.

SUT methods provide scalability and savings for manufacturers, in large part due to the use of durable and sterile disposable bioreactor bags. Instrumentation associated with SUT production must likewise be disposable, unless traditional sensors can be installed, sanitized, and removed for every batch, creating additional complications. The analytical measurement of pH under such conditions creates specific difficulties because pH sensors most commonly use glass bulk sensing technology and must be configured to contact the process media.

Users prefer to use established technologies and electrical signaling methods so they will benefit from known performance and compatibility. However, they also need specific features to take advantage of the SUT processing equipment.

For best flexibility in SUT applications, pH sensors should exhibit a long shelf life so users can keep a reasonable supply on hand and use each one as needed, as well as reducing the costly expense of disposing of bags that reach their expiry date due to sensor lifetime limitations. More importantly, users want the ability to perform a reliable one-point calibration at any time, even when the sensor is in storage before deployment, so they can be assured of proper performance. Finally, the pH sensor form factor must be convenient for installing with single-use bioreactor bags.

Only wetted-storage sensors purpose-built for single-use meet all these criteria.

The state of standard sensors

Sensors designed for dry storage must be wetted with buffer and standardized solutions after installation so they can be calibrated in place and connected to the process, a time-consuming activity, making them less suitable for single use. Traditional wetted sensors may have a shelf life of only 12 months or less and are not designed to withstand single-use sterilization. Early versions of SUT pH sensors experienced high drift, which is problematic for longer production runs.

Ideally, users want the proven performance and connection compatibility of traditional technologies, with packaging suitable for SUT service.

Overcoming SUT obstacles

Updating conventional technology to deliver suitable SUT performance required advances:

• Design a form factor allowing protected wet storage and ready installation into both SUT and established process equipment, while facilitating sensor insertion into the process media.
• Create a buffer supporting long term storage and providing a calibration reference standard.
• Establish a certified factory calibration slope for the sensor in these conditions, enabling a one-point calibration at any time.

The connector—which may also be called a fitting, port, or adapter—uses a standard 1-inch barb for mechanical installation into bioreactor bags and is made from a carefully selected and tested biocompatible material which meets aseptic requirements and withstands gamma radiation sterilization. In the United States, these materials are typically Pharmacopeia Class VI-tested.

Of special interest are the close manufacturing tolerances and precisely sized O-rings, which allow the sensor to be stored in a retracted state in a wetted chamber, with effectively a zero-leak rate. The sensor can be pushed/inserted into contact with process media just prior to batch startup.

Sensors are delivered with a specially developed phosphate-based buffer within the wetted chamber. This buffer delivers a two-year shelf life, and the buffer pH is stable and accurate for sensor calibration. In combination with the factory-supplied sensor calibration slope, it is possible to immediately perform a one-point calibration of the sensor with an accuracy within 0.1 pH.

Note that this initial one-point calibration avoids the cumbersome procedures of filling up process equipment and obtaining a grab sample for an offline measurement, which would be required to validate the functionality of sensors stored under dry conditions. One unique feature enabled by wet storage is that users can validate sensor functionality prior to the start of the process using the internal sensor buffer and sensor diagnostic capabilities. Furthermore, because of optimized conditions for storing the sensor under wet conditions, the sensor is designed to provide a stability of less than 0.005 pH drift per day, making it suitable for long production runs.

Unique pH sensors superior for SUT

Biopharmaceutical production runs are expensive, so end users must continue to holistically evaluate risks, including the incorporation of instruments into this assessment. For many measurements, redundant sensors are installed so production can withstand a single failure.

To address these and other issues, many manufacturers are shifting to SUT production methods to improve flexibility and scalability while cutting costs. However, incorporating reliable and accurate instrumentation compatible with SUT equipment is a must. Traditional instrumentation technologies, enhanced with SUT-specific design features, provide the best solution.

Manufacturers should ensure they are specifying and designing around this new generation of pH instrumentation to realize responsive and reliable measurement for their single-use production systems.

Once in service, of course, users, can evaluate a process grab sample at any time and perform an updated one-point calibration to reset any sensor drift if necessary. Combined, the sensors and housing can withstand pressure up to 30 pounds per square inch gauge and will operate at 39–104 °F, which is well within the limits of what they will see in SUT bioreactor bag service. As is common, the sensor also incorporates an on-board PT-100 RTD used for temperature compensation of the measurement.

Brandon Haschke is a product manager focusing on life sciences for Emerson’s Rosemount instrumentation business. He is currently focusing on measurement devices to meet the needs of the single-use bioprocessing market and the unique challenges of this emerging manufacturing space. Brandon is an active member of BioPhorum and holds a degree in chemical engineering from the University of Minnesota.

The opinions expressed in this blog post are the author’s only and do not necessarily reflect those of Pharmaceutical Processing World or its employees.