Upstream Single-Use Technologies

Pressure Vessels for Biomanufacturing: Basic Considerations for Cleaning and Process Compatibility

Pressure vessels are enclosed containers used to contain liquids, vapors, and gases at pressures that are significantly higher or lower than the ambient pressure of their surroundings. Equipment such as bioreactors, holding tanks, mixing tanks, separators, and heat exchangers all are examples of pressure vessels. As such, they form an integral part of biopharmaceutical manufacturing. Apart from pressure containment itself, a key challenge in building pressure vessels is making them meet the high purity and cleanability requirements of bioprocessing. As…

Expression of Recombinant Antibody Fragments: High-Density Fermentation in Multiuse and Single-Use Systems

Single-use fermentors (SUFs) offer dramatic advantages over traditional stainless-steel clean-in-place (CIP)/sterilization-in-place (SIP) fermentors. Single-use technology eliminates the need for steam, chemicals, and water to clean and sterilize stainless vessels, which provides a direct reduction in capital cost and environmental-impact mitigation. Single-use platforms also increase equipment and process flexibility significantly, making it possible to switch campaigns from one product to another in minimal time, while eliminating cleaning and associated validation steps (1). Both Cytiva and Thermo Fisher Scientific offer SUFs that…

A Strategic Approach to Selecting the Optimal Process Intensification Scenario

Current demands placed on the biopharmaceutical industry are pushing manufacturers toward process intensification, an approach that modifies unit operations or an entire manufacturing process to optimize efficiency. Three common intensification scenarios in upstream processing are seed-train intensification (usually at the n – 1 stage), concentrated fed-batch production, and dynamic perfusion (at the production bioreactor stage). In downstream processes, intensification strategies typically involve moving from single- to multicolumn chromatography. Biomanufacturers can realize several kinds of improvements from intensified processing, including reductions…

The Five Heresies of Cell Culture: Debunking Conventional Wisdom

Cell culture and bioprocessing conventional wisdom remains a hurdle for the wider adoption of more precise tools. It has been more than 60 years since any real progress has been made towards creating a more accurate and reliable way of performing cell culture monitoring to better understand the effects of things like pH and oxygen at the pericellular level. At SBI, we’re developing optical sensing technologies that unlock the “black box” of cell culture to bring actionable insights to scientists…

Measuring Cell Density in HyPerforma S.U.B.s with ABER Futura neotf
Single-Use Sensors

Monitoring critical process parameters (CPPs) and key performance indicators in bioreactor control systems is crucial to ensure proper cell growth and protein production. Today, most of the major biopharmaceutical companies employ capacitance measurement, in R&D and through process development to manufacturing. Owing to the increased use of single-use bioreactors and building on Aber’s experience with single-use capacitance sensors, the latest Futura neotf single-use capacitance sensors have been specifically developed for integration into Thermo Fisher Scientific bioprocess containers (BPCs) for use…

eBook: Bioreactor Sensors —
Inside the Dynamics of Cell Culture

Cell culture monitoring can fall into something like a “black box” conundrum. Efforts to measure key parameters such as pH, glucose, and even cell density require sampling and removal of the contents from a bioreactor. But that procedure can expose both a process and an operator to contamination risks. Emerging bioreactor sensors are designed to address some of those challenges, but the rapid adoption of single-use technologies and the rise of perfusion cell culture have presented obstacles to their implementation.…

Updating the Economics of Biologics Manufacturing with 5,000-L Single-Use Bioreactors: A Paradigm Shift

Single-use technologies enable a flexibility and modularity effectively unattainable with more traditional stainless-steel technologies, particularly in upstream bioprocesses. Single-use bioreactors up to 2,000 L are employed largely in preclinical- and clinical-stage bioprocesses to leverage this flexibility. As products reach commercial maturity, scales larger than 2,000 L frequently become desirable to take advantage of economies of scale. With the typical upper limit of single-use bioreactors at 2,000 L, this has traditionally meant transfer to stainless-steel systems. The introduction of the Thermo…

The Upstream Perspective: Taking Efficiency Beyond Cell-Line Development

With 20 years of experience in the biopharmaceutical industry — at Genentech, Applied Biosystems, Cell Genesys, Cellerant Therapeutics, and Bayer — Yuval Shimoni has written frequently for BioProcess International on a number of production topics. Those have ranged from process improvements and bioreactor scale-down validation, to raw materials management, to addressing variability and virus contamination events. For this featured report, we discussed hardware and instrumentation, quality by design (QbD) and related approaches, and other strategies that can take expediting upstream…

Applications of Disposable Technologies for Upstream Bioprocessing

Over the past 10 years, a number of developments in disposable (limited use) and single-use technologies (SUTs) have been made for different bioprocess operations. Until recent years, much of the industry’s process equipment was sterilized using thermal methods such as autoclaving. Most equipment was reusable and required cleaning and sterilization before use. Such processes required validation and expensive and time-consuming resources. Production facilities relied on hard-piped, inflexible equipment such as large stainless-steel bioreactors and holding tanks. However, advanced SUTs now…

A Rapid, Low-Risk Approach Process Transfer of Biologics from Development to Manufacturing Scale

Successful scale-up of cell culture for manufacturing of biopharmaceuticals gives companies time to accelerate clinical development, product commercialization, and market access (1). Scaling a cell culture process in stirred-tank bioreactors ideally includes optimizing that process at laboratory scale and then transferring it through larger pilot-scale and finally to manufacturing-scale bioreactors (2). This is a complex, time-consuming business that can involve process transfer — sometimes to different geographical locations and through many sizes of bioreactors, each of which can operate according…