Engineering in Life Sciences最新文献

{"title":"RETRACTION: Preparation of a pH-Responsive Chitosan-Montmorillonite-Nitrogen-Doped Carbon Quantum Dots Nanocarrier for Attenuating Doxorubicin Limitations in Cancer Therapy","authors":"","doi":"10.1002/elsc.70033","DOIUrl":"https://doi.org/10.1002/elsc.70033","url":null,"abstract":"<p><b>RETRACTION</b>: E. Rahmani, M. Pourmadadi, S. A. Ghorbanian, F. Yazdian, H. Rashedi, and M. Navaee, “Preparation of a pH-Responsive Chitosan-Montmorillonite-Nitrogen-Doped Carbon Quantum Dots Nanocarrier for Attenuating Doxorubicin Limitations in Cancer Therapy,” <i>Engineering in Life Sciences</i> 22, no. 10 (2022): 634–649, https://doi.org/10.1002/elsc.202200016.</p><p>The above article, published online on 13 September 2022 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editors-in-Chief, Ralf Takors, An-Ping Zeng; and Wiley-VCH GmbH.</p><p>The partial raw data provided by the authors could not address the original concerns, showed inconsistencies with the published results, and ultimately raised additional doubts about the study's overall reliability. Consequently, the editors have lost confidence in the presented data and decided to retract the paper. The authors’ institute has been informed of the allegations and the decision to retract but remained unresponsive. The authors disagree with the retraction.</p>","PeriodicalId":11678,"journal":{"name":"Engineering in Life Sciences","volume":"25 7","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/elsc.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144614971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High Cell Density Perfusion Process of Quail Cells Producing Oncolytic rVSV-NDV","authors":"Lennart Jacobtorweihe,&nbsp;Sven Göbel,&nbsp;Markus Wolschek,&nbsp;Jennifer Altomonte,&nbsp;Udo Reichl,&nbsp;Yvonne Genzel","doi":"10.1002/elsc.70035","DOIUrl":"https://doi.org/10.1002/elsc.70035","url":null,"abstract":"<p>Oncolytic viruses as agents for the treatment of various types of cancer have demonstrated their potential in many clinical studies over the past decades. In particular, rVSV-NDV (a recombinant vesicular stomatitis virus [VSV] construct with fusogenic Newcastle disease virus glycoproteins) shows promising preclinical results. This is due to its safety profile, immunostimulatory effects, and efficacy based on strong syncytia formation. Since virotherapy requires a high input of infectious viruses, efficient production processes are needed. Good manufacturing practice (GMP)-compliant CCX.E10 cells have been previously reported as a high-titer-producing rVSV-NDV candidate in batch mode. Here, semi-perfusion was used to test quail-originated CCX.E10 cells for rVSV-NDV production at high cell densities and in different cell culture media. The best condition was transferred to a full perfusion process in a 3 L bioreactor using a tangential follow depth filtration (TFDF) device for cell retention. The integrated depth filter with a pore size of 2–5 µm allowed 99.9% cell retention at viable cell concentrations (VCCs) of up to 20.6 × 10⁶ cells/mL and continuous virus harvesting. With this setup, we were able to produce 1.33 × 10⁹ TCID₅₀/mL infectious virus with a 5-fold increase in space-time yield (STY) compared to a batch process as a control.</p><p><i>Practical application:</i> Despite significant progress in oncolytic virus development, early research primarily focuses on viral design and therapeutic potential, often overlooking production challenges until later stages. This gap hinders clinical translation, as manufacturing high oncolytic virus doses (up to 10¹¹ infectious particles per injection) remains a major bottleneck. Implementing GMP-compliant cell substrates alongside perfusion cultures is essential to overcoming the low yields of traditional batch production. These advancements have far-reaching implications for reducing costs, increasing dose availability, and accelerating the clinical adoption of this promising immunotherapy.</p>","PeriodicalId":11678,"journal":{"name":"Engineering in Life Sciences","volume":"25 7","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/elsc.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144614972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Production of Bioproducts from Wastewater Treatment Using the Microalga Neochloris oleoabundans","authors":"Fahd Mnasser,&nbsp;Mª Lourdes Martínez-Cartas,&nbsp;Sebastián Sánchez","doi":"10.1002/elsc.70032","DOIUrl":"https://doi.org/10.1002/elsc.70032","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;p&gt;Olive mill wastewater (OMW) poses an environmental risk due to its high chemical oxygen demand (COD). It is also rich in nutrients and organic carbon and has been used in this study together with urban wastewater (UWW) as part of the &lt;i&gt;Neochloris oleoabundans&lt;/i&gt; culture medium in different proportions to analyze the results in the change of proportion in the mixtures, looking for the highest level of wastewater utilization. The objective was to determine both the growth capacity of the microorganism in this medium for subsequent production of bioproducts (such as pigments, crude protein, or lipids) from the generated microalgal biomass, as well as the rate of removal of compounds present in wastewater after treatment, which enables it to be discharged into public canals and used for irrigation. The bioprocesses which were developed in batch photobioreactors of 1 dm&lt;sup&gt;3&lt;/sup&gt;, showed the highest values of maximum specific growth rate and volumetric biomass productivity 0.082 h&lt;sup&gt;−1&lt;/sup&gt; and 3 mg dm&lt;sup&gt;−3&lt;/sup&gt; h&lt;sup&gt;−1&lt;/sup&gt;, respectively. The maximum percentage of crude proteins (49.5%), lipids (51.0%), and carbohydrates (56.0%) we obtained in the final biomass. In this regard, the biggest percentages of organic load removal in the treatment with &lt;i&gt;N. oleoabundans&lt;/i&gt; were 65.66% for total phenolic compounds and 93.7% for COD. In addition, the potential content of salts such as nitrates, nitrites, and orthophosphate decreased for 97.6%, 94.3%, and 69.2%, respectively. Values that show the suitability of &lt;i&gt;N. oleoabundans&lt;/i&gt; for the recovery of bioproducts and the reduction of the pollutant load of wastewater for its reuse in agriculture, increasing the circular bioeconomy in the olive sector.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Summary&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;\u0000 &lt;p&gt;In a region with the highest olive oil production in the world, the high generation of waste from the olive oil industry requires the implementation of solutions to valorize and minimize the waste generated. The treatment of olive mill wastewater, used as a culture medium providing nutrients for the development of microalgae, is a promising procedure.&lt;/p&gt;\u0000 &lt;/li&gt;\u0000 \u0000 &lt;li&gt;\u0000 &lt;p&gt;In this study, the microalgae &lt;i&gt;Neochloris oleoabundans&lt;/i&gt; has been used to treat olive oil mill wastewater, which has allowed high yields to be obtained in the production of biomass that can be transformed into bioproducts such as carbohydrates, proteins, and lipids. In addition, a high yield is obtained in the elimination of components that can be harmful, which is relevant for the reuse of water for irrigation or for discharge into natural watercourses.&lt;/p&gt;\u0000 ","PeriodicalId":11678,"journal":{"name":"Engineering in Life Sciences","volume":"25 7","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/elsc.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144550830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Analysis of Anion Exchange Membrane Adsorbers for Endotoxin Removal During Ultrafiltration and Diafiltration Buffer Preparation","authors":"Sven Heimann,&nbsp;Andrew Vail,&nbsp;Sophie Muczenski,&nbsp;Alexander Faude","doi":"10.1002/elsc.70029","DOIUrl":"https://doi.org/10.1002/elsc.70029","url":null,"abstract":"<p>During the manufacturing of drug substances (DS), endotoxins are a commonly monitored contaminant and checked to ensure the safety and quality of the final product. In this study, we investigated endotoxin removal by commercial anion exchange membrane adsorbers during buffer preparation for an ultrafiltration and diafiltration (UFDF) unit operation as a risk mitigation strategy to meet DS endotoxin specifications. A bracketing design study was used to compare two quaternary amine (Q) modified membranes and one guanidinium functionalized hybrid adsorber for endotoxin removal from spiked buffers representing UFDF start and diafiltration buffer matrices. For the UFDF start buffer, Q-based membrane adsorbers were effective at the removal of endotoxin to the limit of detection in low ionic strength conditions, with one adsorber effective up to 24 mS/cm. Switching to a more complex UFDF diafiltration buffer, Q-based membrane adsorbers were impacted by additional buffer components. The guanidinium-based hybrid membrane adsorber demonstrated endotoxin reduction to the limit of detection from both buffer matrices, showing removal across a wide pH range (4.7–8.3) and conductivity as high as 43 mS/cm. These results demonstrate an operational window for buffers and selected membrane adsorbers to mitigate risk by limiting endotoxin contamination prior to UFDF operations in pharmaceutical applications.</p>","PeriodicalId":11678,"journal":{"name":"Engineering in Life Sciences","volume":"25 7","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/elsc.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144550889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PDMS Membrane Using Phenyl as Rigid Molecular Spacer for Phenol Recovery","authors":"Xiangyan Li,&nbsp;Yan Zhuang,&nbsp;Chang Liu,&nbsp;Chenlin Zhang,&nbsp;Chao Sang,&nbsp;Lankun Wang,&nbsp;Siyu Pang,&nbsp;Hanzhu Wu,&nbsp;Songyuan Yao,&nbsp;Sitong Li,&nbsp;Zhihao Si,&nbsp;Xinmiao Zhang,&nbsp;Peiyong Qin","doi":"10.1002/elsc.70030","DOIUrl":"https://doi.org/10.1002/elsc.70030","url":null,"abstract":"<p>Polydimethylsiloxane (PDMS) is extensively utilized for the recovery of bio-alcohols, but it encounters significant obstacles in volatile organic compounds (VOCs) removal, because of the narrow size for molecules diffusion. In this work, we designed a high-efficiency diffusion channel by introducing phenyl as a spacer into PDMS chains. The monomer divinylbenzene and vinyl-terminated PDMS (vinyl-PDMS) can be chemically crosslinked with thiol-grafted PDMS (thiol-PDMS) based on thiol-ene click reaction. The result shows that the free volume radius (<i>r₃</i>, <i>r₄</i>) has a significant increase after the introduction of divinylbenzene as a spacer, which is beneficial to the transport of phenol diffusion. After a series of optimizations involving the divinylbenzene content, pervaporation (PV) operating temperature, photoinitiator content, and viscosity of vinyl-PDMS, the prepared phenyl-PDMS showed an excellent PV performance for phenol recovery containing 10.9 of separation factor and 3959.66 g m⁻² h⁻¹ of flux as separating 0.1 wt% of phenol/water solution at 70°C. This separation performance is significantly higher than the unmodified PDMS membrane, that is, 2.05 times higher in separation factor and 3.54 times higher in flux. This study provides an effective structure design for the removal of aromatic compounds by enlarging diffusion channels and will make a great contribution to biological medicine and bioengineering.</p>","PeriodicalId":11678,"journal":{"name":"Engineering in Life Sciences","volume":"25 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/elsc.70030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid Recovery and Short-Term Culture of Gastric Circulating Tumor Cells Using Microcavity Array","authors":"Tomoko Yoshino,&nbsp;Tomohiro Takabayashi,&nbsp;Qian Bao,&nbsp;Tsuyoshi Tanaka,&nbsp;Ryo Negishi,&nbsp;Tatsu Shimoyama,&nbsp;Takeshi Sawada,&nbsp;Yusuke Kanemasa,&nbsp;Fumiaki Koizumi","doi":"10.1002/elsc.70026","DOIUrl":"https://doi.org/10.1002/elsc.70026","url":null,"abstract":"<p>Circulating tumor cells (CTCs) hold significant promise for cancer diagnosis, prognosis, and treatment monitoring. We previously developed a technique for a single-cell filtering device known as the microcavity array (MCA), specifically designed for the efficient recovery of CTCs from whole blood samples. Efficient enrichment and release of cells from the MCA remains challenging because of cell adhesion that occurs on the MCA surface during the enrichment phase. This study investigated the effects of surface modification with 2-methacryloyloxyethyl phosphorylcholine (MPC) on the recovery efficiency of cancer cell lines from MCA. Scanning electron microscope (SEM) demonstrated reduced cell-substrate interactions, leading to improved recovery efficiency. Comparative analyses showed that the MCA method provided superior recovery efficiency and reduced processing time compared to traditional methods such as density gradient centrifugation (DGC), while maintaining cell viability and proliferative capacity. CTCs were successfully detected in patients with gastric cancer, and short-term cultures were achieved even when fewer than 20 CTCs per milliliter of blood were isolated. These findings emphasize the importance of surface modification for enhancing CTC isolation and the need for optimized culture conditions. The optimized MCA method offers a promising approach for rapid CTC recovery and potential integration with automated systems.</p><p><b>Practical application</b>: The Microcavity array (MCA) is a device specifically designed for efficient recovery of CTCs from whole blood. However cell adhesion on the MCA surface can limit release efficiency. This study demonstrated that surface modification with MPC signigicantly reduces cell-substrate adhesion, improving recovery efficiency while maintaining cell viability and proliferative capacity. Compared to traditional density gradient centrifugation, the MPC-modified MCA offers shorter processing time and better performance. CTCs were successfully detected in gastric cancer, and short-term cultures were achieved even when fewer than 20 CTCs per mL of blood were isolated. The method supports downstearm applications such as cancer cell characterization and treatment monitoring. With potential for integration into automated system, the optimized MCA provides a practical, scalable solution for clinical liquid biopsy and personalized oncology.</p>","PeriodicalId":11678,"journal":{"name":"Engineering in Life Sciences","volume":"25 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/elsc.70026","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Process Intensification for Recombinant Marburg Virus Glycoprotein Production Using Drosophila S2 Cells","authors":"Sven Göbel,&nbsp;Ludwig Mayerlen,&nbsp;Isabelle Yazel Eiser,&nbsp;Lisa Fichtmueller,&nbsp;David Clements,&nbsp;Udo Reichl,&nbsp;Yvonne Genzel,&nbsp;AxelT. Lehrer","doi":"10.1002/elsc.70022","DOIUrl":"https://doi.org/10.1002/elsc.70022","url":null,"abstract":"<p><i>Marburg marburgvirus</i> (MARV) is a highly virulent human pathogen with limited therapeutic options. Recombinant MARV glycoprotein (GP) produced in <i>Drosophila</i> Schneider 2 (S2) cells has been extensively investigated as potential vaccine antigen with promising efficacy demonstrated in nonhuman primate models. However, the existing production process for MARV-GP involving static batch cell cultures with limited scalability and process control show lower than desirable yields. Here, we assessed various process intensification strategies in single-use orbital shaken bioreactors (OSBs) or rocking bioreactors (WAVE) and report maximum viable cell concentrations (VCCs) of 31.6 × 10⁶ cells/mL in batch, 69.5 × 10⁶ cells/mL in fed-batch (FB), and up to 210.0 × 10⁶ cells/mL in perfusion mode. By changing from a glucose-only feed to a CellBoost5 feed, MARV-GP yields were increased by over two-fold. Implementation of perfusion cultures achieved a peak MARV-GP concentration of 57.4 mg/L and a 540% higher space-time yield compared to the FB process in the 50 L WAVE system. However, maximum cell-specific productivities were achieved at a VCC of 85 × 10⁶ cells/mL and decreased with increasing cell concentrations. Glycoanalysis revealed a uniform paucimannosidic <i>N</i>-glycan profile, predominantly α-1,6-core-fucosylated Man3F (F(6)M3) structures, across all production modes. Notably, transitioning pH control from CO₂ to phosphoric acid shifted glycan profiles toward higher mannose forms, highlighting the influence of culture conditions on glycosylation.</p>","PeriodicalId":11678,"journal":{"name":"Engineering in Life Sciences","volume":"25 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/elsc.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of Exposure Time and Driving Frequency on Cytotoxicity in In Vitro Ultrasound With Constant Mechanical Indices","authors":"Taigo Oyama,&nbsp;Chikahiro Imashiro,&nbsp;Yuta Kurashina,&nbsp;Keita Ando,&nbsp;Kenjiro Takemura","doi":"10.1002/elsc.70011","DOIUrl":"https://doi.org/10.1002/elsc.70011","url":null,"abstract":"<p>Sonochemistry has become increasingly important in bioengineering research, and many in vitro and in vivo bioapplications have been developed. Cytotoxicity is always a concern in its implementation. For in vivo treatments and studies, mechanical index (MI) is known to ensure biocompatibility, and even in vitro MI has been used. Because cell characteristics and acoustic phenomena differ in vitro and in vivo, we questioned using MI in vitro. The in vitro cytotoxicity of ultrasound exposure should be investigated to support the development of cutting-edge sonochemistry. In this study, a system for irradiating cultured cells with 1–2 MHz-range ultrasound was developed to demonstrate the invalidity of employing MI alone in vitro. The results showed that cell damage is defined by the MI, ultrasound frequency, and exposure time, which are new indices for quantifying cell damage. Furthermore, cavitation and acoustic streaming are shown to be the main scientific factors that injure cells.</p>","PeriodicalId":11678,"journal":{"name":"Engineering in Life Sciences","volume":"25 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/elsc.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143949988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design of a Biocatalytic Filter for the Degradation of Diclofenac and Its Ozonation Products","authors":"Dorothee Schmiemann,&nbsp;Jessica Schneider,&nbsp;Marcel Remek,&nbsp;Jeremy Kaulertz,&nbsp;Oliver Seifert,&nbsp;Monika Weidmann,&nbsp;Klaus Opwis,&nbsp;Arno Cordes,&nbsp;Martin Jäger,&nbsp;Jochen Stefan Gutmann,&nbsp;Kerstin Hoffmann-Jacobsen","doi":"10.1002/elsc.70024","DOIUrl":"https://doi.org/10.1002/elsc.70024","url":null,"abstract":"<p>Posttreatment of the effluents from wastewater treatment plants is becoming increasingly important, as the conventional treatment cannot completely remove organic trace contaminants. Promising techniques like chemical oxidation methods, including ozonation, face the challenge of potentially generating more toxic transformation products than their parent substances due to incomplete oxidation. In this work, the laccase from <i>Trametes versicolor</i> was immobilized on a polyester textile to create a biocatalytic textile filter for the posttreatment of organic trace contaminants and their ozonation by-products. Different filter designs for reactive filtration with biocatalytic textiles were implemented on the laboratory scale and tested for their effectiveness in degrading the dye Remazol Brilliant Blue, the pharmaceutical diclofenac, and its ozonation products. The plate module, inspired by lamellar clarifiers and featuring the textile with covalently immobilized enzyme on the lamella surfaces, exhibited the best performance characteristics. Employing this module, a continuous process of diclofenac ozonation and subsequent posttreatment with the biocatalytic filter was conducted. This not only demonstrated the feasibility of continuous biocatalytic wastewater filtration but also highlighted improved degradation efficiencies of ozonation products compared to the batch process using laccase in solution.</p>","PeriodicalId":11678,"journal":{"name":"Engineering in Life Sciences","volume":"25 5","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/elsc.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143901004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influenza A Virus Production Following Quality by Design Principles","authors":"Tilia Zinnecker,&nbsp;Kristin Thiele,&nbsp;Timo Schmidberger,&nbsp;Yvonne Genzel,&nbsp;Udo Reichl","doi":"10.1002/elsc.70027","DOIUrl":"https://doi.org/10.1002/elsc.70027","url":null,"abstract":"<p>Establishing manufacturing processes for cell culture-based pharmaceutical products involves managing multiple parameters that can affect yield and efficiency, as well as process robustness and product quality. Implementing Quality by Design (QbD) principles can support process optimization, while streamlining the chemistry, manufacturing, and control aspects for regulatory approval. In this study, we mimic a QbD approach based on an influenza A virus production process using two clonal suspension Madin-Darby canine kidney (MDCK) cell lines with distinct characteristics. We performed a quantitative risk assessment including biological and technical parameters to identify the Critical Process Parameters (CPPs). To comprehensively study the effects and interactions of four CPPs, we used an Ambr 15 scale-down system following a Design of Experiments (DoE) approach. After data analysis and modeling, we obtained design spaces characterized by high robustness with a less than 1% risk of failure and even some indications for virus titer and yield improvement, while keeping process-related impurities such as DNA and total protein concentration low. These findings were subsequently verified at a more than 100-fold higher working volume. Taken together, our approach may stimulate ideas for the implementation of streamlined process development and regulatory approval in the field of viral vaccine production.</p>","PeriodicalId":11678,"journal":{"name":"Engineering in Life Sciences","volume":"25 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/elsc.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}