Upstream Single-Use Technologies

Evaluating New Film for Single-Use Bags: Growth Performance Studies with Animal and Human Cells

In biopharmaceutical development and manufacturing processes, single-use technology has become widely accepted (1). Storage and cultivation bags are particularly common. They are fabricated from plastics consisting of multilayer films and are typically provided gamma-sterilized by suppliers (2). The bags offer several advantages such as savings in time and cost. Lowered contamination risk results from reduced cleaning and sterilization demands. However, some adverse effects of polymer films on cell growth and metabolism have been reported, both for storage and cultivation bags…

The Case for a Standardized Assay to Test Suitability of Single-Use Systems in Cell Culture Applications

Increased commercial use of single-use systems (SUS) for large-scale biopharmaceutical production creates the need for consensus on industry best practices and standards for materials in SUS components. End users and suppliers are beginning to develop a shared vision of industry needs in such areas (1, 2). For example, highly visible efforts to harmonize extractables testing include contributions from groups such as the BioPhorum Operations Group (BPOG), Bio-Process Systems Alliance (BPSA), Parenteral Drug Association (PDA), ASTM, and ISPE. In addition to…

Single-Use Processing for Microbial Fermentations

During the past decade, single‑use bioprocessing has emerged as a standard platform for current good manufacturing practice (CGMP) mammalian cell culture. Biomanufacturers have come to appreciate the benefits of lower capital and operating costs, reduced contamination risk, continuity from early development through manufacturing, flexibility, and sustainability (1). Disposable cell‑culture vessels have gained wide acceptance because their performance duplicates that of stainless‑steel, fixed‑tank bioreactors, with which manufacturers have extensive experience. This is no accident: Single‑use bioreactors use stainless–steel engineering principles, particularly…

A Novel Seed-Train Process: Using High-Density Cell Banking, a Disposable Bioreactor, and Perfusion Technologies

A typical cell culture process begins with thawing of a cryopreserved cell-bank vial, followed by successive expansions into larger culture vessels such as shake flasks, spinners, Wave bags, and stirred bioreactors (1). When culture volume and cell density meet predetermined criteria, the culture is transferred to a production bioreactor in which cells continue to grow and express product. This approach presents several challenges. Shake flasks or spinners used in the initial stages require manual manipulations inside a laminar flow hood,…

Culturing a Duck ES-Derived Cell Line in Single-Use Bioreactors: A Rapid, Efficient, and Cost-Effective Vaccine Manufacturing System Based on Suspension Culture

Cell substrates managed in controlled culture environments have become, over the past few decades, the subject of intensive technological developments for the biomanufacturing of viral vaccines. The driving force of such work is an expanding demand for safety, high production capacities, cost savings, and flexibility. Egg, tissue, and primary-cell–based manufacturing methods of limited capacity are now considered to be outdated technologies. In the influenza vaccine field, for example, time delays in vaccine delivery (especially during pandemic responses) have increased concerns…

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…