Bioreactors

Platform Solutions for Cell Therapy Manufacturing

Advances in cell therapy have resulted in significant progress toward treating some widespread and difficult diseases, many of which represent unmet medical needs. For example, phase 3 clinical trials are already under way for therapies based on mesenchymal stem cells (MSCs), including therapies for graft-versus-host disease, acute myocardial ischemia, and chronic obstructive pulmonary disease (COPD) (1–3). Successful cell therapy treatments for such afflictions will be not only significant medical breakthroughs, but also in very high demand. However, their commercialization is…

Simplification of Fed-Batch Processes with a Single-Feed Strategy

Chinese hamster ovary (CHO) cells commonly are used to produce recombinant proteins such as monoclonal antibodies (MAbs) for research, diagnostic, and therapeutic purposes. Culture processes typically rely on a fed-batch approach in which a basal medium enables initial cell growth. Concentrated feeds are used to prevent nutrient depletion, thereby extending culture duration and improving cell growth, viability, and protein titer. A neutral pH feed is desirable because culture pH should remain stable after feedings. The extremely low solubility of l-tyrosine…

Design and Performance of Single-Use, Stirred-Tank Bioreactors

Single-use components and systems have been incorporated into many bioprocesses as an alternative to cleanable, reusable systems. A wide range of publications have detailed the reasons for this trend toward a single-use approach. Justification in many cases comes from process-specific benefits such as increased manufacturing flexibility — especially for contract manufacturing organizations (CMOs) — enhanced sterility assurance, elimination of cleaning, reduced capital investment, faster processing times with increased productivity, faster start-up, and other benefits (1). One critical factor in the…

Continuous Cell Culture Operation at 2,000-L Scale

In the biopharmaceutical industry, continuous manufacturing is often cited as a method for increasing the productivity of bioprocesses (1). Compared with batch processing, it has the potential to enable production of more product within a smaller facility footprint — while improving product quality, particularly for sensitive and unstable molecules. Investigation into continuous methods is taking place for both upstream and downstream operations. For the full benefit of continuous processing to be realized, an argument has been made that cell culture,…

Performance Qualification of a Single-Use, Stirred-Tank Bioreactor with CHO-S Cell Culture

The increasing role and importance of cell culture in biophamaceutical manufacturing has led to considerable research and development (R&D) into bioreactor design and performance in recent years. As a result, a greater understanding of bioreactor fluid dynamics and critical physical parameters is now essential to maximize cell growth and productivity. Stirred-tank bioreactors are especially important in this development process because of their favorable properties in areas such as mixing efficiency and homogeneity, energy transfer, and scalability. The design and manufacture…

Bioreactor Manufacturing Platforms for Cell Therapies

As an increasing number of cell therapies move into late-phase trials, developers are considering innovative solutions to address scale-up and commercialization challenges. Many of their questions focus on the technologies and engineering strategies that will be needed to optimize their processes, especially bioreactors. At the January 2016 Phacilitate Cell and Gene Therapy World conference, Siddharth Gupta, a scientist at Lonza (Walkersville, MD), talked about the effects of upstream process decisions on product quality in his presentation “Bioreactor Manufacturing Platforms: So…

Monitoring Live Biomass in Disposable Bioreactors

Often simply referred to as capacitance, radio-frequency (RF) impedance has been used for over two decades to measure online biomass. It is generally regarded as the most robust and reliable method to monitor live-cell concentrations in mammalian cell culture (1). Many biopharmaceutical companies have now made the transition from conventional glass or stainless steel multiuse (MU) vessels to single-use (SU) bioreactors. Disposables are rapidly becoming the preferred platform for new processes requiring current good manufacturing practice (CGMP) compliance. At the…

Using Optical Sensors for Bioprocess Monitoring: A Measurement Technique for Bioprocessors

Over the past decade, the application of chemical optical sensors for bioprocess monitoring has gradually taken roots. Constant further development of this measurement technology and the possibility to manufacture such sensors in various designs (even for single-use applications) have led to new state-of-the-art devices for the biotechnology sector. Chemical optical sensors enable in situ, real-time monitoring of important culture parameters without sampling and therefore without disturbing a culture. Implementing this technology can decrease workloads and deepen knowledge about bioprocesses. In…

Development, Qualification, and Application of a Bioreactor Scale-Down Process: Modeling Large-Scale Microcarrier Perfusion Cell Culture

Qualified scale-down models of large-scale cell culture processes are essential to conducting studies for applications such as investigating manufacturing deviations, enhancing process understanding, and improving process robustness. For example, scale-down models can be used for raw material investigations as well as evaluation and qualification of new good manufacturing practice (GMP) cell banks for manufacturing implementation. Process characterization studies are performed also with qualified scale-down models to improve process consistency (1, 2). Often it is impractical to conduct investigational studies at…

Experiences with a Benchtop-Scale Glass Bioreactor: Engineering Data and Cultivation Results

Animal cell lines (the dominant expression systems in biopharmaceutical production processes) are mostly cultivated in stirred bioreactors (1). Although such bioreactors are widely accepted and applicable over a wide range of scales, engineering data for these systems are still lacking. Nevertheless, studies have shown that the correct choice of key parameters (e.g., power input, tip speed, mixing time, and oxygen mass transfer) can influence the growth of animal cell cultures (2). Therefore, detailed characterization is essential. It enables reliable scaling…