Upstream Single-Use Technologies

Designing the Ideal Bioreactor with Single-Use Technology

    Bioprocessing companies are hoping for a brighter future in biologics manufacturing that will include ever-higher titers of vaccines and therapeutic proteins grown in cell culture. It would also facilitate bioprocess operations without the recurring challenges that stem from process scale-up and human error. Moreover, that future would also comply with increasingly stringent regulatory and current good manufacturing practice (CGMP) requirements while providing better cost controls than we see today. How far away is this future? Perhaps not too…

Method for Preserving Cell Density and Viability in Two-Phase Fed-Batch CHO Culture

Risk of cell-culture contamination is a common concern whenever materials are added to or removed from a bioreactor. It is essential to maintain a sterile barrier and provide containment against intruding organisms during such operations. Many R&D and pilot-scale manufacturing tasks involve flexible, single-use processes with presterilized containment systems in nonclassified laboratory areas. Here, we examine a process that requires substantial manipulation of a culture — first completely removing and later returning the culture to a bioreactor during media exchange…

Upstream Single-Use Bioprocessing Systems

Single-use bioprocessing equipment has become well-accepted technology in a relatively short time. Disposable devices and components have created market niches and new segments that continue to evolve. In this dynamic environment, it is difficult to measure acceptance or assess market growth. Here we project the world market for cell culture single-use systems (SUS) as well as problems affecting that market, including adoption for commercial manufacture. This is based on our 10-year analysis of the industry, with data from our eighth…

An Approach to Design and Performance Testing of an Impeller-Driven Single-Use Mixer

    Single-use technology is now well established for many bioprocessing unit operations, including sterile filtration and product storage, where it provides specific benefits such as elimination of cleaning and cleaning validation, reduced risk of contamination, and enclosed systems for safer handling. Recently, single-use technology has been introduced into more complex unit operations such as purification by chromatography (1), tangential-flow filtration (2), and mixing systems. More complex processing steps, however, present a challenging task for developers of single-use products. Mixing…

Disposable Bioreactor Sensors Play Catch-Up

The evolution of single-use bioreactor (SUB) systems in biologics manufacturing has been rapid and influential. Reliance on efficient and flexible bioreactor technology will be critical for reducing scale-up costs and facility capital expenses as well as aggressively growing biotherapeutic and monoclonal antibody production. The biopharmaceutical industry has seen considerable growth in the proliferation of single-use bioreactor platforms as well as manufacturing areas where these systems are applied. Need for Improved Single-Use Sensors As disposable technologies are widely accepted and established,…

A Biomass Monitor for Disposable Bioreactors

    Of the available on-line biomass assay types, radio-frequency impedance spectroscopy (RFI, often referred to as capacitance) is generally regarded as the most robust and reliable method for monitoring viable biomass during fermentation and cell culture. The first article to show that capacitance could be used to estimate microbial biomass dates back over 20 years (1). Today the technology is routinely used for monitoring and controlling mammalian cell culture processes and high-density yeast and bacterial fermentations in research, process…

The Dinosaurs Reborn: Evaluating Stainless Steel and Disposables in Large-Scale Biomanufacturing

    Although a number of biomanufacturers have adopted disposable technologies for small-scale process design, there has been considerable debate over the role of single-use systems in large-scale biopharmaceutical manufacturing— particularly in retrofitting facilities. Some experts have gone so far as to suggest that large-scale stainless steel fermentors are “dinosaurs,” with their large capacities, long installation lead times, and low flexibility. I advocate a systematic approach to look holistically at possible retrofit technologies in existing (stainless steel) facilities, with particular…

Single-Use Systems As Principal Components in Bioproduction

    Single-use systems (SUS) have become an accepted component of animal-cell–based bioproduction. No longer a merely exciting possibility, they have emerged as a significant and growing resource for companies to use from process development to manufacturing of approved products. Having been examined for years in less regulated environments, off-the-shelf SUS are now in regular use to some extent in nearly every segment of the production train by contract manufacturing organizations (CMOs) and biopharmaceutical companies in mid-scale production applications. For…

Linear Scale-Up of Cell Cultures

    Reusable bioreactors have been the benchmark standard for many decades, during which a large knowledge base on process control and scale-up has been developed. However, single-use bioreactors are increasingly being implemented in modern bioindustrial upstream processes. Many of these bioreactors deviate from the traditional stirred-tank design, but a number of companies have expressed a strong need for single-use bioreactors based on the strirred-tank design. A traditional stirred-tank design would enable users to optimize their scale-up processes based on…

Mixing in Small-Scale Single-Use Systems

    Despite the advantages of presterile, single-use technologies, mixing is one of their most complex applications. Industry has been progressing toward using single-use bag technologies rather than traditional methods of stainless steel tanks and grades A/B processing because of the positive aspects they impart to end users, including a reduced potential for contaminants, cleaning, sterilization, and capital. These technologies offer simplicity and flexibility (1). However, using them for an operation such as mixing can add processing challenges. For example,…