Upstream Processing

Attaining Next-Level Titers in CHO Fed-Batch Cultures

    Taking full advantage of high cell-specific productivity of recombinant proteins requires use of robust fed-batch processes involving addition of one or more concentrated nutrient solutions. Proportionately large amounts of concentrated nutrient supplements are often needed to support the stoichiometrically balanced metabolic requirements of high-density cell cultures. Large feed additions ultimately dilute the final product at harvest, but attempts to minimize feed volumes often lead to multiple concentrated acidic and basic subgroups. Those impart additional complexity to manufacturing processes.…

A New Kinetic Structured Model for Cell Cultivation in a Chemostat

    Mathematically modeling the kinetics of batch and continuous cultivation allows you to not only calculate and evaluate the effects of process parameters, but also to forecast those parameters and duration of cultivation to develop a cost-effective production process. Mathematical modeling microorganism cultivation was intensively developed in the second half of the last century. Equations 1–6: ()   Monod proposed Equation 1 for batch processes in 1942 (1). In that equation, µ and µmax are the specific and maximum…

A Host Cell Protein Assay for Biologics Expressed in Plants

    Host cell proteins (HCPs) can be present in significant amounts in biological products through copurification with a recombinant protein-drug substance. Purified active ingredients developed for human use must be free of all contaminants — including residual HCPs — to minimize the incidence of immunogenicity against a drug product or its trace contaminants (1).   HCP assays allow for monitoring host-related impurities during product development and process development. Most are in the enzyme-linked immunosorbent assay (ELISA) format for detecting…

Novel Single-Use Sensors for Online Measurement of Glucose

    According to an FDA guidance document, process analytical technology (PAT) tools “are intended to support innovation and efficiency in pharmaceutical development” (1). The agency encourages manufacturers to use a PAT framework for developing and implementing effective innovative approaches in development, manufacturing, and quality assurance. The sensors described here are one possible response to the requirement of systems by analyzing and controlling critical cultivation parameters with real-time process measurements.   Working Principle   Glucose was measured using a #CITSens…

How an Obscure Asian Rodent Took Over Biotechnology

The earliest domestic rodents were cavies (“Guinea pigs”) kept as food animals in the Andes since 5000 BC (as shown by mummified cavies) and carried to Europe in the 16th century (Elizabeth I had one as a pet). Although rats weren’t domesticated until the mid-19th century (a byproduct of the blood sport of rat-baiting), mouse selection and breeding began many centuries earlier. Selection of unusually colored mice was first documented ~1100 BC in China, and breeding such “fancy” mice as…

ROUNDTABLE – Single-Use Technologies: Industrialization, Standardization, Regulation – Common Goals and Differing Expectations

As the adoption and maturation of single-use technologies continues to evolve, many end-users are looking for single-use suppliers to standardize products, materials, and equipment in order to improve efficiency and lower costs. An expert group of industry suppliers discusses the pros/cons and differing expectation surrounding this trend.

Bioreactor Design and Bioprocess Controls for Industrialized Cell Processing

It’s official: The “Age of Cell Therapy” has arrived. A robust pipeline of cell therapies, with increasing numbers of both early- and late-stage clinical trials as well as FDA-approved commercial products that have entered the market already, strongly indicates that the cell therapy industry is poised to emerge as a distinct healthcare sector (1). Renewed investor interest and recent activity among major pharmaceutical companies suggest that this industry will rapidly develop the capability and capacity to be a highly competitive,…

A Decade of Bioreactor and Upstream Technologies

A high-quality product begins with efficient upstream process equipment. Ten years ago, manufacturers were still warming up to single-use bioreactors, which were mainly rocking-bag–based solutions. The benefits relating to cleaning and validation were clear, but their use as bioreactor vessels was still new, and stainless steel systems up to 20,000 L in scale were still needed. Today’s facilities are a hybrid of sophisticated single-use components and stainless steel equipment, the mechanisms of both having undergone improvement during the past decade.…