Aqueous Two‐Phase Systems at Large Scale: Challenges and Opportunities

Torres‐Acosta, Mario A.; Mayolo‐Deloisa, Karla; González‐Valdez, José; Rito‐Palomares, Marco

doi:10.1002/biot.201800117

Cited by 75 publications

(40 citation statements)

References 82 publications

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“…However, although the applicability of ATPs has been already demonstrated, protein solubility of some ATPS is still an issue. Furthermore, the lack of industry knowledge on installation, validation, and operation of such systems hampered the adoption of this technique by the industry [152,153].…”

Section: Innovations In Purification Technologiesmentioning

confidence: 99%

Current challenges in biotherapeutic particles manufacturing

Moleirinho

Silva

Alves

et al. 2019

Expert Opinion on Biological Therapy

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Introduction: The development of novel complex biotherapeutics led to new challenges in biopharmaceutical industry. The potential of these particles has been demonstrated by the approval of several products, in the different fields of gene therapy, oncolytic therapy, and tumor vaccines. However, their manufacturing still presents challenges related to the high dosages and purity required. Areas covered: The main challenges that biopharmaceutical industry faces today and the most recent developments in the manufacturing of different biotherapeutic particles are reported here. Several unit operations and downstream trains to purify virus, virus-like particles and extracellular vesicles are described. Innovations on the different purification steps are also highlighted with an eye on the implementation of continuous and integrated processes. Expert opinion: Manufacturing platforms that consist of a low number of unit operations, with higheryielding processes and reduced costs will be highly appreciated by the industry. The pipeline of complex therapeutic particles is expanding and there is a clear need for advanced tools and manufacturing capacity. The use of single-use technologies, as well as continuous integrated operations, are gaining ground in the biopharmaceutical industry and should be supported by more accurate and faster analytical methods.

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Section: Innovations In Purification Technologiesmentioning

confidence: 99%

Current challenges in biotherapeutic particles manufacturing

Moleirinho

Silva

Alves

et al. 2019

Expert Opinion on Biological Therapy

View full text Add to dashboard Cite

show abstract

“…To maximize the large-scale use of LBS requires an ideal optimization technique at where the system can perform at its best desired performance for various application. A recent review by Torres-Acosta et al, (2019) has comprehensively evaluated the strategies to incorporate the LBS technologies in the industry [91]. One of the most frequent optimization techniques used is univariate optimization or known as one-factor-at-a-time (OFAT) analysis is where a single parameter at the time after the other is selected based on its best performance.…”

Section: Future Prospect and Challenges Of Lbs Applicationmentioning

confidence: 99%

Liquid Biphasic System: A Recent Bioseparation Technology

et al. 2020

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A well-known bioseparation technique namely liquid biphasic system (LBS) has attracted many researchers’ interest for being an alternative bioseparation technology for various kinds of biomolecules. The present review begins with an in-depth discussion on the fundamental principle of LBS and this is followed by the discussion on further development of various phase-forming components in LBS. Additionally, the implementation of various advance technologies to the LBS that is beneficial towards the efficiency of LBS for the extraction, separation, and purification of biomolecules was discussed. The key parameters affecting the LBS were presented and evaluated. Moreover, future prospect and challenges were highlighted to be a useful guide for future development of LBS. The efforts presented in this review will provide an insight for future researches in liquid-liquid separation techniques.

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“…Recent large-scale work are scarce and ATPS should be pushed more strongly into commercial implementation. 29 These results are important as a base for the future study on the increase of sample loading and how to make ATPS a more intensive unit operation. This is of critical importance, as the water content can be displaced to capture more product of interest, potentially decreasing production costs, as demonstrated here, as long as recovery and purity are not significantly compromised.…”

Section: Analysis Of Atps Sample Loading On Cog/dosementioning

confidence: 98%

Economic evaluation of M13 bacteriophage production at large‐Scale for therapeutic applications using aqueous Two‐Phase systems

Torres‐Acosta

González‐Mora

Ruiz‐Ruiz

et al. 2020

J of Chemical Tech & Biotech

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BACKGROUND: Bacteriophages are bionanoparticles with several applications in different biotechnology-based products. Among them, vaccines have the potential to treat antibiotic-resistant bacteria and parasitic infections. Traditional methods for their recovery and purification rely on precipitation with polyethylene glycol (PEG) and NaCl. However, the applicability of such an approach is limited, due to large-scale technical constrains. Recently, our research group developed a bacteriophage M13 recovery and purification strategy using Aqueous Two-Phase Systems (ATPS), simplifying the methodology and, potentially, reducing costs. This work aims to develop an economic contrast between ATPS and the traditional PEG precipitation method at different operation scales (10 to 1000 L bioreactor volume) to determine the applicability of the ATPS methodology at large scale. For this, the effect of ATPS volume ratio (V R), sample loading, and materials discount over production cost were analyzed. RESULTS: Results indicate that as the discount on material costs increases, ATPS becomes a more affordable unit operation, from a bioreactor scale of 10 L at 0% discount to 410 L at 90% discount (US$ 52.2 to $1.72 per gram, respectively). Material cost contribution is a parameter that needs attention when working with ATPS, as it is the core for the system construction. Methods for reducing their contribution are highly relevant and should be further investigated. CONCLUSION: Employment of economic analyses help to discover critical parameters for a bioprocess, such as material costs for ATPS. This economic analysis work serves as a platform for new strategies for the recovery of bacteriophage and bacteriophage-like particles using ATPS-based technologies.

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Aqueous Two‐Phase Systems at Large Scale: Challenges and Opportunities

Cited by 75 publications

References 82 publications

Current challenges in biotherapeutic particles manufacturing

Current challenges in biotherapeutic particles manufacturing

Liquid Biphasic System: A Recent Bioseparation Technology

Economic evaluation of M13 bacteriophage production at large‐Scale for therapeutic applications using aqueous Two‐Phase systems

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