Industrial Production of Therapeutic Proteins: Cell Lines, Cell Culture, and Purification

Zhu, Marie M.; Mollet, Mike; Hubert, René; Kyung, Yun Seung; Zhang, Green G.

doi:10.1007/978-3-319-52287-6_29

Cited by 33 publications

(32 citation statements)

References 102 publications

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“…However, cell lines may still lose their special characteristics and need regular quality control and characterisation [ 1 ]. Numerous mammalian cell lines have been developed for the industrial production of biotherapeutic proteins, notably the Chinese hamster ovary (CHO) expression systems [ 44 ]. However, more development is needed to express larger ECM proteins using these systems.…”

Section: Discussionmentioning

confidence: 99%

“…Cell expansion on flat-plate culture platforms is laborious and costly. One single batch of industrial CDM manufacturing can easily consume billions of cells, making cell expansion a financially critical step [ 44 ]. Industrial cell culture platforms need to provide the high throughput requirement while maintaining the consistency of the culture condition.…”

Section: Scale-up Technologies For Cdm Productionmentioning

confidence: 99%

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Towards Biomanufacturing of Cell-Derived Matrices

Chan

et al. 2021

IJMS

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Cell-derived matrices (CDM) are the decellularised extracellular matrices (ECM) of tissues obtained by the laboratory culture process. CDM is developed to mimic, to a certain extent, the properties of the needed natural tissue and thus to obviate the use of animals. The composition of CDM can be tailored for intended applications by carefully optimising the cell sources, culturing conditions and decellularising methods. This unique advantage has inspired the increasing use of CDM for biomedical research, ranging from stem cell niches to disease modelling and regenerative medicine. However, while much effort is spent on extracting different types of CDM and exploring their utilisation, little is spent on the scale-up aspect of CDM production. The ability to scale up CDM production is essential, as the materials are due for clinical trials and regulatory approval, and in fact, this ability to scale up should be an important factor from the early stages. In this review, we first introduce the current CDM production and characterisation methods. We then describe the existing scale-up technologies for cell culture and highlight the key considerations in scaling-up CDM manufacturing. Finally, we discuss the considerations and challenges faced while converting a laboratory protocol into a full industrial process. Scaling-up CDM manufacturing is a challenging task since it may be hindered by technologies that are not yet available. The early identification of these gaps will not only quicken CDM based product development but also help drive the advancement in scale-up cell culture and ECM extraction.

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Section: Discussionmentioning

confidence: 99%

Section: Scale-up Technologies For Cdm Productionmentioning

confidence: 99%

Towards Biomanufacturing of Cell-Derived Matrices

Chan

et al. 2021

IJMS

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“…The supply of oxygen to the cells can easily be the limiting factor in achieving high cell densities (Ozturk, 1996;Zhu et al, 2017). The design of the mass-flow controller and sparger require consideration.…”

Section: Bioreactor Designmentioning

confidence: 99%

The design basis for the integrated and continuous biomanufacturing framework

Coffman

Bibbo²,

Brower

et al. 2021

Biotech & Bioengineering

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An 8 ton per year manufacturing facility is described based on the framework for integrated and continuous bioprocessing (ICB) common to all known biopharmaceutical implementations. While the output of this plant rivals some of the largest fed‐batch plants in the world, the equipment inside the plant is relatively small: the plant consists of four 2000 L single‐use bioreactors and has a maximum flow rate of 13 L/min. The equipment and facility for the ICB framework is described in sufficient detail to allow biopharmaceutical companies, vendors, contract manufacturers to build or buy their own systems. The design will allow the creation of a global ICB ecosystem that will transform biopharmaceutical manufacturing. The design is fully backward compatible with legacy fed‐batch processes. A clinical production scale is described that can produce smaller batch sizes with the same equipment as that used at the commercial scale. The design described allows the production of as little as 10 g to nearly 35 kg of drug substance per day.

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“…Criteria followed for protein formulation development should essentially be equipped with suitable units for keeping dust, fumes and particulate matters at bay [53]. Advanced instrumentation facility comprising of all the high-end instruments such as UV, CD, HPLC (high-performance liquid chromatography), fluorescence spectroscopy, mass spectrometry, and SDS-PAGE for protein analysis should be present in the manufacturing unit [54]. The efficacy of protein formulation is determined by the assessment of its stability conducted using ambient conditions such as refrigerators, agitators, stability chambers and alike.…”

Section: Strategies For Oral Protein Formulationsmentioning

confidence: 99%

Current Status and Perspectives of Oral Therapeutic Protein and Peptide Formulations: A Review

Manu

Firdose

Jayanthi

et al. 2021

JPRI

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Medicinal formulations have evolved from the use of small molecules that act by blocking various receptors. On the contrary, therapeutic proteins are a class of medicines that have gained increased popularity owing to its low toxicity, high stability and exquisite specificity. Oral delivery of protein drugs is a very interesting but a highly challenging area of medicine that requires advancements in terms of bioavailability of oral drugs. The main objective of the present review is to provide a systematic overview of the various physiological barriers of delivery of therapeutic proteins and novel approaches available in this field in order to counter these physiological barriers. Advances in terms of inhibitors of proteases, permeation enhancers, mucoadhesives, short peptide conjugates, particulate delivery system including nanoparticles. Oral therapeutic proteins face challenges with regard to oral bioavailability, stability of the protein and reproducibility. Among the various strategies, a co-administration of permeation enhancers with protease inhibitors have proven most effective, while particulate delivery system is still under clinical studies in order to be establishes as a method. Overall, a thorough and focused research with sufficient knowledge on the structure-function relationship, substrate specificity and physiological parameters can deliver a potent therapeutic protein with high efficiency.

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Industrial Production of Therapeutic Proteins: Cell Lines, Cell Culture, and Purification

Cited by 33 publications

References 102 publications

Towards Biomanufacturing of Cell-Derived Matrices

Towards Biomanufacturing of Cell-Derived Matrices

The design basis for the integrated and continuous biomanufacturing framework

Current Status and Perspectives of Oral Therapeutic Protein and Peptide Formulations: A Review

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