OR WAIT null SECS
The shift to single-use technologies is driving the need for innovation in PAT-friendly sensor technologies.
As the use of single-use technologies in bioprocessing continues to advance and therapeutic molecules increase in complexity, process analytical technology (PAT)-friendly tools strive to keep pace. Data needs have also changed, with demand for robust and meaningful data becoming more important to understanding biomanufacturing processes and to implement process controls. The question remains, however, about whether the current availability of single-use sensors and probes are sufficient to meet these changing needs.
Sensors and probes are needed to collect critical data during bioprocess steps, particularly data on pH, dissolved oxygen (DO), and cell viability. The industry, however, still needs improved sensor technologies. Examples of specific improvements needed are high-resolution tools with low-limit detection thresholds, the ability to capture high frequency measurements that do not require repeated calibration over the course of a single batch production, and the ability to have online characterization of proteins in a bioreactor in a reliable, reproducible, and robust manner as well as with high precision (1).
The shift toward single-use technologies in bioprocessing also poses challenges, namely that single-use technologies can often be incompatible with sensor technology. This incompatibility prompts the need for innovation in single-use or single-use-compatible sensors, probes, and related technologies. Examples of such innovation is the sheathing of sensors or probes in disposable coverings that are compatible with single-use biobag ports and the development of single-use sensors and probes (2).
To discuss the challenges and improvements made in PAT-friendly sensor technology, BioPharm International spoke with Kelsey Mato, PhD, market segment manager for Process Analytics at Hamilton Company.
BioPharm: What is the importance of probes and sensors to the implementation of PAT in biologics manufacturing?
Mato: Probes and sensors are at the center of the PAT initiative (they are the PA after all). The goal with PAT is essentially to continuously measure as many parameters as possible for the deepest understanding of your process. Sensors are the tool used to gain those measurements, giving you more parameters, more data. Much of the sensor information is used in real time to automate process control (like DO measurements for oxygen sparging), but the data can also be used for process monitoring and even post-process calculations. This can be important for troubleshooting, optimization, or even a use that isn’t determined until the need arises. Having more sensors in a bioreactor that are collecting as much information about the process as possible is the same as having more tools in the toolbox.
BioPharm: With the increasing adoption of single-use technologies in bioprocessing, what is the impact on sensor and probe usage, development, and utilization?
Mato: Sensors need to adapt to the needs of single use. Development of single-use sensors needs to retain the same robustness and precision as in reusable sensors. This is especially true at facilities using both. In addition to mirroring the expectations of reusable sensors, single-use sensors need to be able to integrate into the single-use bags or reactors and meet the requirements of those pieces as well. This typically means the ability to withstand gamma sterilization, prolonged dry storage, and the assembly needs to not leak. All of these requirements lead to the assurance that use of the sensors should not change substantially from their reusable counterparts.
BioPharm: Why is it important to develop more single-use probes and sensors; what benefit would this be for PAT? Are currently available single-use probes and sensors adequate for the job (i.e., have they benefitted PAT implementation and have they generated robust data)?
Mato: Single-use sensors are very important for reaching PAT alignment. The proper sensors for the application are critical to process understanding in exactly the same way as in steel or glass reactors. There are lots of possible issues with using reusable sensors in a single use process, so the more parameters that are available in SU [single use] format, the better.
This ensures that the measurement is optimized for the type of integration. There are currently a few good options on the market, but there needs to be a full suite of options available on each bag or SU reactor. Implementation of SU sensors have enabled people to increase the degree of process understanding. Many of the sensors available as SU (especially intelligent and digital) have been shown to provide reliable and robust data. When sensors are developed specifically for single-use applications but with all the benefits of reusable sensors, real-time, robust data can be acquired.
BioPharm: What is the importance of having robust data collected throughout the bioprocessing stages; how does this benefit biologic production?
Mato: Robust data are critical for maximum process understanding. Any signal interference, for example, may hide the true value of the measurement. A noisy signal or otherwise imprecise signal reduces the possibility for an accurate deadband. Robust, reliable data also ensure that no process events are missed and provide the most efficient troubleshooting tool for batch-to-batch or scale-to-scale reproducibility. To this point, the biggest benefit of robust data is the ability to automate and control the process based on these data. If a measurement signal is not robust, automated control becomes less reliable and higher risk. Robust data are also required for the utilization of soft sensors. Using the data from two or more sensors to calculate an additional parameter that is not being physically measured is an incredibly powerful approach to furthering process understanding and optimization and to truly reaching PAT compliance. If the data going into these calculations are not robust, there is no way the data coming out can be.
BioPharm: Between in-line, on-line, and at-line data collection, which of these offers the most meaningful way to collect bioprocessing data and offers the most useful point at which to involve single-use probes and sensors?
Mato: In-line data collection should always be the main goal for process analytics when the option is available. The PAT initiative guidelines clearly emphasize the benefits of in-line measurement, but to reiterate, in-line measurements have no time delay, no changes to sample conditions (e.g., temperature changes from handling), and the least complicated set up. This makes in-line sensing the best way to get real-time data that is truly representative of the bioreactor as a whole.
1. C. Challener, BioPharm International 43 (6) 36–40 (2019).
2. P. Thomas, “Bioprocess Sensors: PAT Means Proliferation,” pharmamanufacturing.com, Dec. 16, 2009.
Feliza Mirasol is the science editor for BioPharm International.
Vol. 33, No. 11
When referring to this article, please cite it as F. Mirasol, “Single-Use Sensors Increase Process Understanding,” BioPharm International 33 (11) 2020.