Upstream process intensification and continuous manufacturing
Publication date: December 2018Source: Current Opinion in Chemical Engineering, Volume 22Author(s): Chun Chen, H Edward Wong, Chetan T GoudarManufacturing process of biopharmaceuticals usually starts from culturing recombinant protein producing cells, predominately Chinese Hamster Ovary (CHO) cells, in bioreactors. Currently, fed-batch cell culture process is the most common upstream process method due to its operational simplicity and industrial familiarity. Intensified cell culture process, enabled by perfusion and other technologies, offers many benefits over traditional fed-batch cell culture mode. In this review, we d...
Source: Current Opinion in Chemical Engineering - November 21, 2018 Category: Chemistry Source Type: research

Process and metabolic engineering perspectives of lactate production in mammalian cell cultures
Publication date: December 2018Source: Current Opinion in Chemical Engineering, Volume 22Author(s): Mauro Torres, Claudia Altamirano, Alan J DicksonMammalian cells present the main expression platforms for production of recombinant therapeutic proteins. To cope with the increased demand for these therapeutics, more productive manufacturing processes have been developed using high-density cultures and enriched feeds/media. This has dramatically increased the productivity of mammalian cells in culture but this is accompanied by an increased production and accumulation of lactate in cultures, with the pattern of phasic produc...
Source: Current Opinion in Chemical Engineering - November 17, 2018 Category: Chemistry Source Type: research

Observation and simulation of hydrogen storage via spillover
Publication date: September 2018Source: Current Opinion in Chemical Engineering, Volume 21Author(s): Cheng-Yu Wang, Cheng-Wei Chang, Yi-Ju Wu, Angela D LuekingHydrogen spillover refers to catalytic dissociation of hydrogen molecules followed by surface diffusion to the catalytic support. This mechanism has been proposed as a means to initiate hydrogen storage at ambient temperature. When catalytic dissociation of hydrogen is used to initiate room temperature hydrogen storage, this initiates weak chemisorption. High variations in experimental uptake, combined with theoretical calculations that are inconsistent with this mec...
Source: Current Opinion in Chemical Engineering - November 16, 2018 Category: Chemistry Source Type: research

Cell-free biomanufacturing
Publication date: December 2018Source: Current Opinion in Chemical Engineering, Volume 22Author(s): Bradley C Bundy, J Porter Hunt, Michael C Jewett, James R Swartz, David W Wood, Douglas D Frey, Govind RaoSince its early development and use to decipher the genetic code, in vitro or ‘cell-free’ systems have been used as an important research tool to understand biochemical mechanisms and metabolic pathways. More recently, due to important engineering advances the technology is rapidly becoming a biomanufacturing platform for protein therapeutics, vaccines, enzyme biocatalysts, fuels, and commodity chemicals. Here we rep...
Source: Current Opinion in Chemical Engineering - November 14, 2018 Category: Chemistry Source Type: research

Impact of nucleotide sugar metabolism on protein N-glycosylation in Chinese Hamster Ovary (CHO) cell culture
Publication date: December 2018Source: Current Opinion in Chemical Engineering, Volume 22Author(s): Harnish Mukesh Naik, Natalia I. Majewska, Michael J. BetenbaughN-Glycosylation, a critical quality attribute that affects therapeutic protein efficacy, half-life and stability, occurs through a series of reactions where nucleotide sugars are sequentially attached to the asparagine residue of a protein. Nucleotide sugar abundance can impact glycan complexity and the final glycosylation profile. Recent advances in analytical technology have allowed for a faster, more efficient detection and quantification of nucleotide sugars....
Source: Current Opinion in Chemical Engineering - November 12, 2018 Category: Chemistry Source Type: research

A critical assessment of present hydrogen production techniques: is solar cracking a viable alternative?
Publication date: September 2018Source: Current Opinion in Chemical Engineering, Volume 21Author(s): Nesrin Ozalp, Michael Epstein, Richard Davis, Cedric Ophoff, Ian VinckThere has been extensive R&D on thermochemical production of hydrogen and synthesis gas via concentrated solar energy. A major objective of these efforts was to generate fuel for ground transportation, either as synthetic liquid fuel via Fischer-Tropsch or as pure hydrogen for fuel cell vehicles as compressed gas on board. In parallel, batteries for use in electric vehicles have made substantial progress primarily with respect to their energy density and ...
Source: Current Opinion in Chemical Engineering - October 30, 2018 Category: Chemistry Source Type: research

Considerations for risk and control of mycoplasma in bioprocessing
Publication date: December 2018Source: Current Opinion in Chemical Engineering, Volume 22Author(s): Phillip Angart, Casey Kohnhorst, Meng-Jung Chiang, Nilou Sarah ArdenAdventitious agents are a safety risk to biomanufacturing pipelines, from cell line development to upstream and downstream processes. A contamination event can and has effectively shut down plant operations and resulted in drug shortages. To ensure the highest levels of product quality and patient safety, comprehensive control strategies must be in place. Mycoplasma are particularly challenging due to their prevalence in the environment, their small size tha...
Source: Current Opinion in Chemical Engineering - October 26, 2018 Category: Chemistry Source Type: research

Site-specific integration ushers in a new era of precise CHO cell line engineering
Publication date: December 2018Source: Current Opinion in Chemical Engineering, Volume 22Author(s): Nathaniel K Hamaker, Kelvin H LeeGraphical abstract (Source: Current Opinion in Chemical Engineering)
Source: Current Opinion in Chemical Engineering - October 24, 2018 Category: Chemistry Source Type: research

Sensors for biomanufacturing process development: facilitating the shift from batch to continuous manufacturing
Publication date: December 2018Source: Current Opinion in Chemical Engineering, Volume 22Author(s): Timothy R Holzberg, Valencia Watson, Sheniqua Brown, Abhay Andar, Xudong Ge, Yordan Kostov, Leah Tolosa, Govind RaoThe biopharmaceutical industry has traditionally utilized batch manufacturing strategies for production, but continuous manufacturing has been explored as an alternative production method in recent years because of the potential financial and quality benefits. The complex nature of this manufacturing method requires robust online process analytical technology (PAT) that can effectively characterize continuous pr...
Source: Current Opinion in Chemical Engineering - October 24, 2018 Category: Chemistry Source Type: research

Beyond preclinical research: production of CHO-derived biotherapeutics for toxicology and early-phase trials by transient gene expression or stable pools
Publication date: December 2018Source: Current Opinion in Chemical Engineering, Volume 22Author(s): Matthew Stuible, Frank van Lier, Matthew S Croughan, Yves DurocherChinese Hamster Ovary (CHO) cells are a workhorse expression host for production of protein-based biotherapeutics. Expression from stably transfected CHO clones is just one means of recombinant protein production in CHO cells, but lower productivity and longstanding regulatory guidelines have restricted the use of alternative approaches, such as non-clonal stable pools and transient gene expression (TGE), for drug manufacturing. Recently, the performance of st...
Source: Current Opinion in Chemical Engineering - October 23, 2018 Category: Chemistry Source Type: research

Current status and future challenges in continuous biochromatography
Publication date: December 2018Source: Current Opinion in Chemical Engineering, Volume 22Author(s): Sebastian Vogg, Thomas Müller-Späth, Massimo MorbidelliContinuous processing of biopharmaceuticals has seen increased interest in recent years due to more competition in the market as well as broader pipelines asking for more flexible and therefore intensified processes. For downstream processing, chromatography remains the separation process of choice due to its very high resolving power. While continuous counter-current processes have been implemented successfully in other sectors such as the petrochemical or small-molec...
Source: Current Opinion in Chemical Engineering - October 17, 2018 Category: Chemistry Source Type: research

Progressing from transient to stable packaging cell lines for continuous production of lentiviral and gammaretroviral vectors
Publication date: December 2018Source: Current Opinion in Chemical Engineering, Volume 22Author(s): Jaeyoung Park, Sarah Inwood, Srivalli Kruthiventi, Jackson Jenkins, Joseph Shiloach, Michael BetenbaughLentivirus and other retroviral vectors are useful tools to engineer chimeric antigen receptor (CAR) T cells which are designed to target tumor cells in the growing field of gene therapy. Several efforts have been made to improve vector packaging systems including plasmid systems and envelopes and develop stable packaging cell lines (PCLs) in order to improve the productivity and safety by eliminating cytotoxicity of HIV-1 ...
Source: Current Opinion in Chemical Engineering - October 11, 2018 Category: Chemistry Source Type: research

Continuous manufacturing of viral particles
Publication date: December 2018Source: Current Opinion in Chemical Engineering, Volume 22Author(s): Sonia Gutiérrez-Granados, Francesc Gòdia, Laura CerveraCell-based production of viral particles has gain interest in the last years due to promising therapeutic applications. In the field of vaccination, novel vaccines are required to face the new pathogen outbreaks, and rapid and more efficient processes are required to respond as fast as possible to the vaccination demand worldwide. On the other hand, viral vector-driven gene therapies have demonstrated to be efficient and safe in numerous clinical trials, and three of t...
Source: Current Opinion in Chemical Engineering - October 11, 2018 Category: Chemistry Source Type: research

Challenges to industrial mAb bioprocessing—removal of host cell proteins in CHO cell bioprocesses
Publication date: December 2018Source: Current Opinion in Chemical Engineering, Volume 22Author(s): Sarah Gilgunn, Jonathan BonesMonoclonal antibodies hold a steadfast lead in the ever-expanding biologics marketplace and have revolutionized the treatment of a wide variety of illnesses. The prominence of mAbs as therapeutic agents brought with it the need for large scale production of these drugs, which in turn highlighted the need for improvements in cell culture processes to raise product titres. Increased product titres shifted bioprocessing concerns downstream as with increased titre brought along the increased expressi...
Source: Current Opinion in Chemical Engineering - October 10, 2018 Category: Chemistry Source Type: research

Computational tools for predicting and controlling the glycosylation of biopharmaceuticals
Publication date: December 2018Source: Current Opinion in Chemical Engineering, Volume 22Author(s): Cleo Kontoravdi, Ioscani Jimenez del ValGlycosylation is a critical quality attribute of biopharmaceuticals because it is a major source of structural variability that influences the in vivo safety and therapeutic efficacy of these products. Manufacturing process conditions are known to influence the monosaccharide composition and relative abundance of the complex carbohydrates bound to therapeutic proteins. Multiple computational tools have been developed to describe these process/product quality relationships in order to c...
Source: Current Opinion in Chemical Engineering - October 9, 2018 Category: Chemistry Source Type: research