Continuous downstream processing of biopharmaceuticals

Jungbauer, Alois

doi:10.1016/j.tibtech.2013.05.011

Cited by 282 publications

(214 citation statements)

References 115 publications

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“…The balance between costs and product quality can be achieved by, for example, the utilization of cheap materials in the construction of the PBRs (Tredici, 1999) and the full automation of the process (Marchetti et al, 2012). The utilization of downstream processes operating in continuous mode (e.g., harvesting, cell rupture and product extraction) should be fully explored and optimized, since it allows a real-time monitoring and control of the process, increasing the productivity and decreasing the investment, which are important economic advantages over typical batch processes (Jungbauer, 2013). Other strategies to decrease the production costs in continuous systems are discussed in detail in Section 3.5.…”

Section: Strategies To Overcome Limitationsmentioning

confidence: 99%

“…Whereas upstream processing comprises steps like the inoculum preparation, cultivation in the seed PBR and the full-scale cell cultivation, downstream processing includes all the process steps from cell harvest to the final product. Depending on the product of interest, after the biomass recovery, several processes such as biomass processing (e.g., drying), cell disruption, metabolite extraction from the biomass and purification of the extract product can be, or not, performed (Jungbauer, 2013;Mirón et al, 2003). Although with different operational dynamics, the flow diagrams for continuous and batch downstream processing are essentially the same.…”

Section: Downstream Processesmentioning

confidence: 99%

“…However, the utilization of downstream processes in continuous mode, allows higher productivity and flexibility due to the possibility to monitor and control the downstream steps in real time (Jungbauer, 2013). Additionally, it can be very useful in processes in which a toxic, inhibitory, volatile or extracellular compound is present (Niedermeyer et al, 2014).…”

Section: Downstream Processesmentioning

confidence: 99%

See 2 more Smart Citations

Continuous cultivation of photosynthetic microorganisms: Approaches, applications and future trends

Fernandes

Mota

Teixeira

et al. 2015

Biotechnology Advances

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The possibility of using photosynthetic microorganisms, such as cyanobacteria and microalgae, for converting light and carbon dioxide into valuable biochemical products has raised the need for new cost-efficient processes ensuring a constant product quality. Food, feed, biofuels, cosmetics and pharmaceutics are among the sectors that can profit from the application of photosynthetic microorganisms. Biomass growth in a photobioreactor is a complex process influenced by multiple parameters, such as photosynthetic light capture and attenuation, nutrient uptake, photobioreactor hydrodynamics and gas-liquid mass transfer. In order to optimize productivity while keeping a standard product quality, a permanent control of the main cultivation parameters is necessary, where the continuous cultivation has shown to be the best option. However it is of utmost importance to recognize the singularity of continuous cultivation of cyanobacteria and microalgae due to their dependence on light availability and intensity. In this sense, this review provides comprehensive information on recent breakthroughs and possible future trends regarding technological and process improvements in continuous cultivation systems of microalgae and cyanobacteria, that will directly affect cost-effectiveness and product quality standardization. An overview of the various applications, techniques and equipment (with special emphasis on photobioreactors) in continuous cultivation of microalgae and cyanobacteria are presented. Additionally, mathematical modeling, feasibility, economics as well as the applicability of continuous cultivation into large-scale operation, are discussed.

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Section: Strategies To Overcome Limitationsmentioning

confidence: 99%

Section: Downstream Processesmentioning

confidence: 99%

Section: Downstream Processesmentioning

confidence: 99%

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Continuous cultivation of photosynthetic microorganisms: Approaches, applications and future trends

Fernandes

Mota

Teixeira

et al. 2015

Biotechnology Advances

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“…The abbreviation MoBiDiK means modular bioproduction, being disposable and continuous. For further information, the reader is recommended to overviews of the availability of continuous bioprocessing technology [29,30] and current opinions on the future of bioprocessing [31,32]. Case studies for the applicability of the SPI cont might, therefore, arise soon.…”

Section: Discussionmentioning

confidence: 99%

Production Rate‐Dependent Key Performance Indicators for a Systematic Design of Biochemical Downstream Processes

Brandt

Schembecker

2016

Chem Eng & Technol

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Key performance indicators have become a common tool in bioprocess development, as they allow an objective and independent rating and ranking of process alternatives screened. A disadvantage of all key performance indicators developed so far is their strong focus on costs, which makes them neglect the influence of the production rate on the profit of the process. But, since both production costs and production rate have an equally strong impact, both should be considered when decisions have to be made. Therefore, two new key performance indicators are introduced in this work, one for batch and one for continuous processing. They combine product yield, purity performance, variable manufacturing costs, and production rate to one objective. Thereby, misguided trade-offs between these four individual measures can be replaced by one key performance indicator. This ensures a systematic development of biochemical downstream processes.

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“…Similar to solid dosage forms, continuous manufacturing is also of major importance for biopharmaceutical products 1,13 . Recently, an innovative continuous freeze-drying concept was proposed which tackles the higher outlined disadvantages associated with the traditional lyophilisation process 14,15 .…”

Section: Introductionmentioning

confidence: 99%

Noncontact Infrared-Mediated Heat Transfer During Continuous Freeze-Drying of Unit Doses

Bockstal

Meyer

Corver

et al. 2017

Journal of Pharmaceutical Sciences

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Recently, an innovative continuous freeze-drying concept for unit doses was proposed, based on spinning the vials during freezing. An efficient heat transfer during drying is essential to continuously process these spin frozen vials. Therefore, the applicability of non-contact infrared (IR) radiation was examined. The impact of several process and formulation variables upon the mass of sublimed ice after 15 minutes of primary drying (i.e., sublimation rate) and the total drying time was examined. Two experimental designs were performed in which electrical power to the IR heaters, distance between the IR heaters and the spin frozen vial, chamber pressure, product layer thickness and five model formulations were included as factors. A near-infrared (NIR) spectroscopy method was developed to determine the endpoint of primary and secondary drying. The sublimation rate was mainly influenced by the electrical power to the IR heaters and the distance between the IR heaters and the vial. The layer thickness had the largest effect on total drying time. The chamber pressure and the five model formulations had no significant impact on sublimation rate and total drying time, respectively. This study shows that IR radiation is suitable to provide the energy during the continuous processing of spin frozen vials.

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Continuous downstream processing of biopharmaceuticals

Cited by 282 publications

References 115 publications

Continuous cultivation of photosynthetic microorganisms: Approaches, applications and future trends

Continuous cultivation of photosynthetic microorganisms: Approaches, applications and future trends

Production Rate‐Dependent Key Performance Indicators for a Systematic Design of Biochemical Downstream Processes

Noncontact Infrared-Mediated Heat Transfer During Continuous Freeze-Drying of Unit Doses

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