An Introduction to "Recent Trends in the Biotechnology Industry: Development and Manufacturing of Recombinant Antibodies and Proteins".

The production of the first therapeutic proteins in the early 1980s heralded the launch of the biopharmaceuticals industry. The number of approved products has grown year on year over the past three decades to now represent a significant share of the entire pharmaceuticals market. More than 200 therapeutic proteins have been approved, approximately a quarter of which are represented by monoclonal antibodies and their derivatives.

Equipment characterization to mitigate risks during transfers of cell culture manufacturing processes.

The production of monoclonal antibodies by mammalian cell culture in bioreactors up to 25,000 L is state of the art technology in the biotech industry. During the lifecycle of a product, several scale up activities and technology transfers are typically executed to enable the supply chain strategy of a global pharmaceutical company. Given the sensitivity of mammalian cells to physicochemical culture conditions, process and equipment knowledge are critical to avoid impacts on timelines, product quantity and quality.

Online integrity monitoring in the protein A step of mAb production processes-increasing reliability and process robustness.

The purification of recombinant proteins and antibodies using large packed-bed columns is a key component in most biotechnology purification processes. Because of its efficiency and established practice in the industry, column chromatography is a state of the art technology with a proven capability for removal of impurities, viral clearance, and process efficiency. In general, the validation and monitoring of chromatographic operations-especially of critical process parameters-is required to ensure robust product quality and compliance with health authority expectations.

Implementing high-temperature short-time media treatment in commercial-scale cell culture manufacturing processes.

The production of therapeutic proteins by mammalian cell culture is complex and sets high requirements for process, facility, and equipment design, as well as rigorous regulatory and quality standards. One particular point of concern and significant risk to supply chain is the susceptibility to contamination such as bacteria, fungi, mycoplasma, and viruses. Several technologies have been developed to create barriers for these agents to enter the process, e.

Influence of pluronic F68 on oxygen mass transfer.

Pluronic F68 is one of the most used shear protecting additives in cell culture cultivations. It is well known from literature that such surface-active surfactants lower the surface tension at the gas-liquid interface, which influences the mass transfer. In this study, the effect of Pluronic F68 on oxygen mass transfer in aqueous solutions was examined.

Chromatographic peak alignment using derivative dynamic time warping.

Chromatogram overlays are frequently used to monitor inter-batch performance of bioprocess purification steps. However, the objective analysis of chromatograms is difficult due to peak shifts caused by variable phase durations or unexpected process holds. Furthermore, synchronization of batch process data may also be required prior to performing multivariate analysis techniques.

Optimizing capacity utilization by large scale 3000 L perfusion in seed train bioreactors.

Increasing capacity utilization and lowering manufacturing costs are critical for pharmaceutical companies to improve their competitiveness in a challenging environment. Development of next generation cell lines, improved media formulations, application of mature technologies and innovative operational strategies have been deployed to improve yields and capacity utilization. This article describes a large-scale perfusion strategy for the N-1 seed train bioreactor that was successfully applied to achieve higher inoculation cell densities in the production culture.

Insights into large-scale cell-culture reactors: II. Gas-phase mixing and CO₂ stripping.

Most discussions about stirred tank bioreactors for cell cultures focus on liquid-phase motions and neglect the importance of the gas phase for mixing, power input and especially CO(2) stripping. Particularly in large production reactors, CO(2) removal from the culture is known to be a major problem. Here, we show that stripping is mainly affected by the change of the gas composition during the movement of the gas phase through the bioreactor from the sparger system towards the headspace.

Insights into large-scale cell-culture reactors: I. Liquid mixing and oxygen supply.

In the pharmaceutical industry, it is state of the art to produce recombinant proteins and antibodies with animal-cell cultures using bioreactors with volumes of up to 20 m(3) . Recent guidelines and position papers for the industry by the US FDA and the European Medicines Agency stress the necessity of mechanistic insights into large-scale bioreactors. A detailed mechanistic view of their practically relevant subsystems is required as well as their mutual interactions, i.