Searching for the Holy Grail of Single-Use Solutions

By Barb Paldus, Finesse Solutions, LLC

“Single-use sensors are the critical missing element for upstream bio-processing”
-Barb Paldus

Many biotechnology companies are transitioning their stainless steel infrastructure to single-use or disposable systems in order to reduce scale-up costs and facility capital expenses. As single-use bioreactors have matured, their market acceptance has rapidly expanded. The move to disposables is, in many instances, driven by reduction in sterilization and cleaning requirements, improved plant flexibility for multi-product manufacturing, reduced product changeover costs and faster time to market for new products. As the average titer (g/L) produced continues to increase, the size of bioreactor vessels required in manufacturing will decrease; this trend will further accelerate the transition to disposable bioreactors in production environments.

In order to fully enable the single-use paradigm, the automation software, hardware and single-use sensors must be designed specifically for this application. Automation hardware systems used with single-use bioreactors must be flexible, in order to adapt to the different processes that can be run in a multi-product facility. Hardware must be user-friendly and plug-and-play with a wide variety of external equipment, such as pumps, scales and off-line analyzers. In addition, and especially for CMO customers, the bioreactor control system must have a modular design, allowing fast and easy re-configuration of the bioreactor train for different bioreactor sizes and types, as well as different processes or cell lines, such as batch, fed-batch or perfusion.

Automation software should allow rapid scalability of a process through advanced process models and smart algorithms, as well as ease of data collection and analysis. The software should allow easy process re-configuration through drop-down menus without any programming, and allow the use to save and load process recipes for accelerated process scale-up or transfer. The software should be vessel agnostic, so that it can be used with glass vessels and single-use rocker or stirred-tank bioreactors, to provide a seamless integrated solution from R&D through production. For true scalability, the software must be developed with GAMP5 methods and therefore be validatable for cGMP applications. 

Single-use sensors, to date, are the critical missing element for upstream bio-processing.  Specifically, there is a significant need for disposable sensors for dissolved oxygen, pH, temperature and pressure, which are pre-inserted into the single-use bioreactor bag and gamma irradiated with the bag so that the entire system arrives sterile, and the time from unpacking the bag to inoculation is minimized. Smart sensors which arrive in the bioreactor pre-calibrated and thereby minimize operator time during process setup, are the industry's ideal. 

A visionary supplier will provide turnkey, configure-to-order measurement and automation solutions for different single-use bioreactor types. This supplier will also provide full support for its systems, including installation, training, validation packages (FAT, SAT, IQ/OQ), leachables/extractables certifications for all single-use components, and service/maintenance programs. Moreover this supplier would have cell culture capability and be able to provide complete bioreactor and sensor solutions, but also cell line development and media optimization services, in order to minimize the risk to an end user of transitioning a process to single-use, and scaling up production. Taking one last step, this supplier would also be able to provide complete, single-use solutions for downstream applications and optimize the entire process end-to-end with yield modeling.

Today, there is no such ideal supplier. Several alliances in the industry have formed, but no one true stop-shop has yet emerged. In addition, most suppliers have a very limited cGMP installed base and track record in single-use systems, and have not made serious inroads into single-use downstream processing. The single-use flexible factory concept remains the holy grail. Nonetheless, in the next few years, especially with the ongoing industry consolidation between larger and smaller players, we expect that such an ideal supplier will eventually emerge.

Barb Paldus was most recently the CTO of Picarro, a company she founded in 1998. At Picarro, she was responsible for technology strategy, research and business development, which led to a solid-state Cyan laser product in 2003 and cavity ring-down spectroscopy products in 2004. Barb is currently a partner at Skymoon Ventures. She received both her Ph.D. (1998) and M.S.E.E. (1994) degrees in electrical engineering from Stanford University, and her BS (1993) in electrical engineering/applied mathematics from the University of Waterloo.