Author Archives: Gerhard Greller

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…

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…

Consistently Superior Cell Growth: Achieved with New Polyethylene Film Formulation

During the past decade, single-use bioprocessing bags and bioreactors have gained a significant foothold in the biopharmaceutical industry because they offer a number of advantages over traditional stainless steel equipment, especially for clinical production, multiproduct facilities, and emerging economies. At the same time, some companies are concerned that plastic materials might release potentially toxic substances that could affect cell growth and product titers (1). In a worst-case scenario, they could even compromise drug safety when a company uses disposable bags…

Robust and Convenient Single-Use Processing: The Superior Strength and Flexibility of Flexsafe Bags

With the increased use of disposable bioprocessing bags in all critical process steps of the biopharmaceutical drug production, there is a growing requirement for high-quality, robust, and easy-to-handle bioprocessing bags. The new generation of films and bags must combine multiple mechanical, physical, and chemical properties to make these products suitable and scalable for all processing steps in upstream, downstream, and final filling operations, including cell culture in rocking motion and/or stirred-tank, single-use bioreactors as well as storage, mixing, shipping, and…

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…

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

During the past decade, single-use bioreactors have become widely accepted for use in cell culture process development and clinical manufacturing. Their key benefits over stainless steel bioreactors are flexibility, cost, and time savings associated with the reduction of cross-contamination risks (1). Here, we describe our approach to development and qualification of the Biostat STR single-use, stirred-tank bioreactor. Unlike other stirred single-use bioreactors, it offers a similar design to that of well-established, conventional (stainless steel) stirred-tank bioreactors. Disposability of the single-use…

Large-Scale, Insect-Cell–Based Vaccine Development

    Vaccines are among biotechnological products characterized by continuous growth over the past decade. According to a 2011 report, the global vaccine market is expected to reach US$34 billion in sales by 2013 (1). Much development can be ascribed to vaccine treatments for cancer, autoimmune, and infectious diseases (which have risen significantly) as well as the growing worldwide population and emergence of new pandemics. Although to date the main health impact of vaccines is still in disease prevention, the…