Upstream Single-Use Technologies

Measuring Pressure at Very Low Levels with High Accuracy in Single-Use Systems: Improved Performance and Single-Use System Testing

Measuring pressure in single-use systems (SUS) has become an integral part of both upstream and downstream bioprocess operations. Articles have been published on filtration applications (1), and integration into other SUS has been widely adopted. Additionally, information is available on low-pressure applications such as how to prevent overpressurization in single-use bioreactors (2). However, as users and applications both become more sophisticated, improved performance is sought for low-pressure applications (<1 psi) such as in single-use bioreactors. The reasons are two-fold: First,…

Polymer Resins: Building Blocks for Single-Use Bioreactor Components

Single-use manufacturing equipment for the production of certain biological compounds (e.g., recombinant proteins from mammalian cell cultures) makes good sense. Such equipment reduces water and energy use, decreases the need for equipment sterilization and waste treatment, and optimizes space in a manufacturing facility. But consider the plastic resins used to construct the disposable parts of such equipment. In BPI’s April 2014 issue, Tony Kingsbury discussed the fundamentals of how plastics are made. In this second installment of BPI’s series on…

Single-Use, Stirred-Tank Bioreactors: Efficient Tools for Process Development and Characterization

During the past decade, single-use bioreactors have become widely accepted as an alternative to conventional stainless steel or glass bioreactors for clinical manufacturing and process development. In the biopharmaceutical industry, glass bioreactors are used mainly for process development and optimization, but also scale-down models for process characterization. So it is of significant importance that such vessels replicate the design of production-scale bioreactors for both reusable and single-use applications. Stirred-tank bioreactors with 2-L, 5-L, and 10-L working volumes have proven to…

Superior Scalability of Single-Use Bioreactors

During the past several years, single-use bioreactors have been gradually established in modern biopharmaceutical processes (1, 2). This adoption is directly linked to their unique ability to enhance flexibility and reduce investment and operational costs. Furthermore, production output can be increased, and time to market is shortened (3). Today a wide variety of single-use bioreactors exists for the cultivation of mammalian and insect cells (4), whereas only limited solutions are available for microbial cultures (5). Typically, processes are established and…

Integrated Optical Single-Use Sensors: Moving Toward a True Single-Use Factory for Biologics and Vaccine Production

Through the past decade, single-use bioreactors for culturing mammalian and insect cells have been widely adopted in preclinical, clinical, and production-scale biopharmaceutical facilities (1, 2). With such bioreactors in operation, monitoring and control of process parameters is vital for ensuring critical quality attributes (CQAs) of biologicals or vaccines are met for production of a safe product. Traditionally, bag-based and bench-top vessels have been fitted with conventional pH and dissolved oxygen (DO) probes similar to those used in stainless steel or…

Development and Qualification of a Scalable, Disposable Bioreactor for GMP-Compliant Cell Culture

During the development of single-use, stirred-tank bioreactors (e.g., BIOSTAT STR bioreactors), different phases can be distinguished (Figure 1). First, a clear definition of the intended application and all related requirements should be captured in a user requirement specification (URS). Based on that, the single-use bioreactor design phase and the material selection phase are initiated, both closely linked to each other. During the proof-of-concept phase, relevant component- and product-based tests are established and realized to ensure URS compliance. Finally, the qualification…

Verification of New Flexsafe STR Single-Use Bioreactor Bags: Using a CHO Fed-Batch Monoclonal Antibody Production Process at 1,000-L Scale

In the past decade, single-use bioreactors have gained wide acceptance for biomanufacturing. The biopharmaceutical industry is increasingly interested in performing modern production processes in single-use facilities. That trend is driven by the time and cost benefits of single-use technologies, as well as the enhanced manufacturing flexibility they offer (1). With single-use bioreactors increasingly used in late-phase clinical trials and commercial production, their quality, reliability, and assurance of supply becomes more critical. Many industry experts consider process control of film and…

Pressure Decay Method for Postinstallation Single-Use Bioreactor Bag Testing

Single-use technology is well accepted today, and manufacturers’ quality assurance programs ensure leak-free single-use bags upon delivery. But what about risks involved with installation and other handling errors? Operator training and implementation of suitable standard operating procedures (SOPs) are mandatory, but should they be the only ways to mitigate the risk of failures? In addition, more companies are advocating the use of ballroom concepts (1) for the manufacture of biopharmaceutical drug substances and drug products. However, how do you prove…

Industry Experts Convene in New York to Discuss Latest Innovations: A BPI Special Report

As the biopharmaceutical industry continues to mature and grow, so too does the need to educate a broader audience of biopharmaceutical professionals interested in hearing, understanding, and applying the latest science and technology trends that support and in many cases are transforming today’s bioprocesses. To reach this extended and engaged audience, BioProcess International created the BPI Theater Series: a live, interactive program that provides bioprocessing content to traditional, noncore biopharmaceutical conference programs. It provides attendees with the opportunity to interact…

One Billion Mesenchymal Stem Cells in an Eppendorf BioBLU 5c Single-Use Bioreactor at 3.75-L Scale

For BPI’s inaugural “Ask the Expert” webcast, Ma Sha (Eppendorf’s director of technical applications) fielded questions related to his upcoming poster presentation at IBC’s Single-Use Applications for Biopharmaceutical Manufacturing in Boston this month: “One Billion Mesenchymal Stem Cells in Eppendorf BioBLU 5c Single-Use Bioreactor 3.75-L Scale”. Eppendorf R&D Labs is formerly New Brunswick Scientific, which was acquired by Eppendorf in 2007. Sha’s Presentation Our focus recently had been large-scale stem-cell applications in bioreactors. We chose to work on mesenchymal stem…