To celebrate the 20th anniversary of BioProcess International, industry suppliers were asked to respond to a questionnaire about the important technologies, trends, and manufacturing innovations that have shaaped their companies and the entire industry over the past two decades.
What has been the most important scientific or technological innovation in the past 20 years of bioprocessing? I have been in the industry since the mid-1990s, and clearly the most significant evolution in biomanufacturing has been the widespread implementation of single-use technology. Many people would not have imagined making life-saving drugs and vaccines in 1,000-L plastic bags. The technology has moved far beyond plastic buffer- and media-storage bags and disposable filters. Single-use aseptic connectors, sensors, and other technologies have made single-use processing a reality. Such innovations cater to the needs of the industry to bring a plethora of biologically derived products based on leaps in product development. Single-use technology and high cell-culture titers accelerate speed to market, especially for products with small batch sizes for targeted therapies. Those innovations have eliminated the extensive capital equipment requirements for water-purification systems and steam-generation systems (e.g., for clean-in-place and steam-in-place (CIP/SIP) for stainless-steel processing equipment) and the need for large amounts of water and energy for producing steam.
What scientific and technical developments have surprised you the most over the past 20 years? Cell-culture productivity has gone beyond what many people imagined. There were alternative technologies such as producing proteins in milk and plants that seemed promising but became more subdued as cell-culture productivities increased dramatically and remained the dominant production template.
What has been the most notable development in bioprocess business strategy? Primarily, suppliers of filters and chromatography media evolved to be suppliers of complete hardware and single-use fluid path assemblies. Suppliers rapidly developed infrastructure for designing and producing complex single-use fluid path assemblies. Extensive workforces and cleanroom spaces also had to be developed, and end users depended on those suppliers to keep their manufacturing processes running.
Which of your companyâ€™s products or services have been most successful in the past 20 years? PendoTECH was founded in 2005 with a goal of simplifying process control systems for key unit operations based on the implementation of single-use technology, including elimination of CIP/SIP. The company realized that single-use sensors were required to find a holistic solution beyond control systems. In late 2006, the company launched its line of single-use pressure sensors. That led to a two-track development of separate product lines: single-use sensors and process control systems.
Single-use pressure sensors were implemented to help solve problems involving monitoring pressures on single-use bioreactors â€” where pressure limits can be low, and over-pressurization could lead to safety and product-loss issues. Pressure sensors also were used in other bioprocess operations in which pressure is a critical process parameter that must be monitored and controlled for both performance and safety. Widespread adoption of those products by both suppliers of single-use systems and end users has brought PendoTECH significant growth. Part of the success of single-use pressure sensors is their excellent quality and impeccable performance as process volumes have increased. A single-use assembly is as good as its weakest part, and a failure can be extremely expensive. The range of sizes to adapt to difference scales and types of processes has continued to broaden as more single-use processes are implemented in the bioprocessing industry. Pressure monitoring with single-use sensors has challenged PendoTECH to develop complementary sophisticated electronics that integrate with its customersâ€™ control systems.
Process control systems migrated from customized solutions that were based on customersâ€™ user-requirement specifications (URS) to a standard offering key unit operations in purification such as normal-flow filtration (NFF) and tangential-flow filtration (TFF). By listening to our customers and continually improving our set of products, PendoTECH has grown its process control system product line. Hundreds of systems are being used daily by leading industry companies to develop their processes. Those systems are heavy on data acquisition, taking advantage of increasing PC processing power over the years to create fingerprints of processes for optimization before process scale-up. Open platform communications (OPC) server functionality has been implemented on all systems to enable data sharing with common databases such as the PI historian system from OSIsoft, thereby speeding analysis of data coming from different process systems and analyzers, concurrently.
What opportunities are ahead? The main opportunity for the industry in the next five to 10 years is to implement continuous processing to increase productivity, decrease facility size, and implement Industry 4.0. Almost all other industrialized manufacturing sectors have gravitated to continuous processing. The bioprocess industry has been striving for that, and their progress is likely to accelerate as huge investments are made in that area. Continuous processing could be the preferred production platform in the future if regulatory and technical challenges can be overcome.
With Industry 4.0 and the industrial internet of things (IIoT), biomanufacturers can take advantage of strategic planning, strong visions, and technological advances to create a disruptive force for operating efficiently. IndustryÂ 4.0 and IIoT enable connectivity between business systems and manufacturing systems to share data. Part of data collection relates to learning about a process in depth. That includes determining which process variables and/or conditions can affect process outcomes such as product quality attributes (PQAs). Process analytics practice is evolving toward the use of artificial intelligence (AI) for making process adjustments to maintain parameters within certain boundaries and ensuring positive outcomes from production runs. Those adjustments could prevent failures (which can be expensive in terms of lost raw materials) that compromise the ability of a company to meet customer demand. An enterprise resource planning system can feed a manufacturing execution system (MES) to initiate a production run consisting of 10 or more unit operations (often in series) that must be orchestrated optimally over many weeks.
Industry 4.0 can maximize the likelihood of production-run success by using process analytics and process monitoring and control. With SCADA and a high-level control system that connects and communicates with different process unit operations, process monitoring and control can be conducted in a timely way. A SCADA is a computer system for gathering and analyzing real-time process data. A supervisory system sends commands to a process controller, which performs control actions. Using Industry 4.0 increases success rates, thus decreasing relative cost of goods. Networked connectivity of a control system with other systems (e.g., a quality control laboratory information management system) can be used to create electronic batch records and speed up product release. Two key concepts to keep in mind are communication and connectivity. At the SCADA/control system level, the control system, self-contained unit operations (skids), sensors, and other devices must be connected and communicate in the same â€ślanguage.â€ť Connectivity often is defined by a physical layer, consisting of a hardware device that creates the physical connection between devices and must be common among devices for them to communicate.
End users and suppliers of equipment and control systems must work closely together to ensure that there is connectivity to enable all systems to communicate with other and to enable successful implementations of a continuous, fully automated process framed around the operations benefits of Industry 4.0.
How has your companyâ€™s role changed over the past 20 years? PendoTECH was founded as a start-up with aspirations to grow with the industry in biomanufacturing and process development. The company has grown with the industry, and its product lines have expanded to meet the industryâ€™s needs. The company continues to strive to listen to its customersâ€™ suggestions and future desires. Over the past 20 years, the company built an organizational structure, enabling it to grow from both a product development point of view and as a manufacturing organization to meet industry demands. The key along the way was to hire the right team members that fit the company culture and to encourage a positive work environment to stimulate innovation.
What advice do you have for new life-science professionals? Continue your education to stay on top of this rapidly evolving field. Take calculated risks in trying new positions to expand your capabilities. Combining different positions within your field can help you develop a skill set that is valuable to your company and elevate you to more challenging and interesting opportunities as companies expand and need talent.
What lies ahead for you and your company? In March of 2021, PendoTECH was acquired by Mettler Toledo, a leading global supplier of process analytical technologies with a heavy presence in the bioprocessing space of pH and dissolved oxygen measurement technologies for bioreactors. PendoTECH, as a business unit of Mettler Toledo, has the potential to further scale its business and jointly develop products to meet industry requirements for enhancing product quality through on-line analytics. My company is working diligently to increase sensor-manufacturing capacity to keep up with increasing product demands.
Jim Furey is general manager at PendoTECH.