Today’s demanding biopharmaceutical manufacturing operations require careful control of process conditions, whether during cell culture, purification or drug product formulation. Process sensors play a critical role in enabling high-performance manufacturing by providing real-time visibility into how a process attribute is changing as well as the ability to correlate that change with the stage of the process.
“In the pharmaceutical industry, it is extremely valuable to see how an attribute changes with time and correlate that change with part of the process,” says L. Harry Lam, Ph.D., a biopharmaceutical manufacturing industry expert. “It is imperative to have effective equipment that provides reliable measurements.”
With the critical role that process sensors play in bioprocesses, selecting the best sensors for the job is the key to process success and understanding. To successfully deploy sensors, pharma manufacturers should consider following these principles:
• Define objectives, and find a sensor technology that provides the information needed to accomplish your goals.
• The sensible choice depends on the situation; for example, the size and age of the manufacturing operation and relevant regulatory guidelines help determine what is sensible in addition to the particular product being manufactured.
• Successful sensor deployment requires follow-through to implement the system correctly.
MATCHING SENSOR TECHNOLOGY WITH GOALS
The right choice of sensor begins with the particular manufacturing challenge being addressed. Different products require different controls and possibly different sensors. The first principle for successfully deploying sensors is that a manufacturer must clearly define the problem to be solved and identify the sensor technology that provides the data required to solve it.
“You must know what is important about the process, and then you can pick the sensor,” says Tina Larson, a bioprocess industry expert who heads up manufacturing operations and engineering for a major pharmaceutical company.
This principle is especially important to remember for organizations scouting new technologies. Although new technology is exciting and touted for its promise, focus must be maintained on identifying the best suited sensor technology to measure the target critical process parameter. “The key question is,” warns Larson, “do the data give you what you need to solve your problem?” There is no shortage of challenges that drive manufacturing operations to invest in new sensor technology. “Investment in new sensor technology is driven by those manufacturing challenges where there is the greatest amount of uncontrolled variability,” says Larson. “In biopharmaceutical manufacturing, that is the cell culture stage.”
Accurately measuring cell mass in cell cultures, for example, is an unsolved problem that still eludes effective measurement. Another area of uncontrolled variability is glycosylation in cell cultures; researchers need a better understanding of the biological control of glycosylation to develop proper sensors for this complex problem.
“SUCCESS” DEPENDS ON THE SITUATION
In addition to seeking a sensor technology that provides the data needed to manage a critical process attribute, regulatory and business considerations also impact bioprocess sensor implementation decisions.
The recent U.S. Food and Drug Administration Process Analytical Technology (PAT) initiative is driving a closer look at bioprocess analytics by pharmaceutical manufacturers. The PAT guidelines urge manufacturers to update their sensor technology as needed so that they have data on those process parameters that affect the quality of their products. For example, antibody production is a core process in biopharmaceutical manufacturing. Methods for purifying antibodies and producing the antibody protein are well established, and bioprocess sensors such as pH and DO are standard. These sensors allow operators to manage critical process parameters in real time. Further, having routinely collected the data, they are now available for use in analyzing issues when they do occur, perhaps even allowing manufacturers to spot success trends not previously recognized.
The PAT guidelines point to best practices that ensure critical attributes are monitored and that provide insurance against process failures. Other factors to be considered in making a new sensor deployment decision are the size and age of the manufacturing plant, which affect the cost of making the change. “There must be an important business case for going through the change process,” states Larson.
Process sensors measure a range of attributes, from traditional pH and dissolved oxygen (DO) to cutting-edge attributes whose relevance is still being proven. Whether a new sensor is state-of-the-art, a workflow innovation and/or cutting edge affects the implementation decision.
State-of-the-art sensors are newer versions of well-established sensors. They measure critical attributes that facilitate high-performance plant operation and biopharmaceutical production. “State-of-the-art” might mean more accurate, more stable, or easier to calibrate. Two examples of state-of-the-art sensors are optical DO sensors (see Technology Spotlight 1) and “smart” sensors (see Technology Spotlight 2).