Today’s renewed interest in perfusion culture is due to an increased awareness of its advantages, some general improvement in equipment reliability, and a broadening of operational skills in the biomanufacturing industry. Some misperceptions persist, however, according to a 2011 review by Eric Langer (1). Our view here of the history of perfusion and fed-batch processes includes some discussion of technological process improvements and challenges that the bioprocess industry faces. A team of authors at Serono in Switzerland wrote…
Upstream Processing
Meeting Increased Demands on Cell-Based Processes By Using Defined Media Supplements
Rapidly increasing demand for cell-derived products has placed huge pressures on the biomanufacturing industry’s production capacity requirements. Media development strategies continue to be a primary focus for optimizing output from cell culture systems. Animal cells used in manufacturing protein products have complex nutrient requirements specific for each cell type, clone, and product. Individual nutrient requirements were once addressed by using serum-based media rich in growth factors and supplements, which provided an optimal culture environment for cell growth and productivity (1).…
Trends and New Technology in Vaccine Manufacturing
Significant changes are sweeping the vaccine manufacturing industry. Demand for human vaccines is predicted to grow significantly — in part driven by needs in emerging countries, where only small fractions of their large and growing populations has access to vaccines. Sustained growth is expected to yield a vaccine market of US$25 billion by the year 2015 (1). Relatively low immunization rates in the Asia–Pacific regions represent significant untapped potential for vaccine manufacturers. Growing populations, increased government funding, and increasing personal…
Pseudomonas fluorescens Expression Technology for Subunit Vaccine Production and Development
New methods and platforms for rapid development and production of effective subunit vaccines have become a 21st-century imperative. Not only is it important to rapidly express and produce a large number of antigens, but those antigens must be expressed and folded such that their effectiveness in preclinical studies is predictive of their potential effectiveness as vaccines. This task has created a bottleneck in vaccine development because recombinant protein expression is difficult and time-consuming, involving a large number of variables. Highly…
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…
NIR Spectroscopy Analysis of Phosphate Salts
Confirmation of raw material quality is a vital part of biopharmaceutical manufacturing processing. Incorrect or poor-quality vendor materials account for a considerable portion of failed and recalled product. To prevent these expensive problems, strict quality control (QC) procedures are often implemented and used to screen for inappropriate incoming materials. QC procedures commonly used are chemical tests that involve removing samples to a laboratory and performing, which can at times be complex, time-consuming, and laborious protocols. A common test procedure that…
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,…
Development of an In-House, Process-Specific ELISA for Detecting HCP in a Therapeutic Antibody, Part 2
During biopharmaceutical manufacturing, final drug products can get contaminated with host-cell proteins (HCPs) derived from a production cell line. HCPs can elicit adverse immune responses, so regulatory authorities require accurate monitoring of their presence and concentration in final drug products. Because they are robust and offer good throughput, enzyme-linked immunosorbent assays (ELISAs) are the first choice for HCP detection to monitor product quality. Generic ELISA kits are commercially available for HCP detection with a number of commonly used…
A Novel Dry-Format Supplement for CHO Cells
The biotechnology industry is continually looking for new methods of improving titer of biotherapeutic proteins. Numerous reports show that nutrient supplementation improves productivity several-fold (1,2). Maintaining cells in a viable and productive condition is the ultimate goal and generally involves adding small volumes of concentrated nutrients to cell cultures. Important parameters for designing a nutrient supplement include ease of use, operator and site safety, and product storage footprint at a manufacturing facility. Traditionally, these supplements come as concentrated…
New Plant Expression Systems Drive Vaccine Innovation and Opportunity
Plant expression systems are emerging as fast and inexpensive methods for producing vaccines. Someday, plants may surpass mammalian and even many microbial systems in efficiency and cost-benefits for the manufacture recombinant proteins. This is particularly so for the rapid manufacture of truly large-scale (million- or even billion-dose) vaccine antigens. Whether grown as single cells or tissues in photosynthesis reactors, as whole plants in controlled laboratory situations, or cultivated in fields of transformed food-commodity plants (e.g., rice, potatoes, or tobacco), plants…