1,720,960 research outputs found
Influenza A Virus Production Following Quality by Design Principles
No full textABSTRACT 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
Optimising and adapting perfusion feeds in serum-free medium to intensify CAR-T cell expansion in stirred-tank bioreactors
No full textThe ex vivo expansion of autologous chimeric antigen receptor (CAR) T cells to reach a therapeutic dose significantly prolongs manufacturing time and increases overall costs. The common use of animal- or human-derived serum in T cell expansion culture media further contributes to process variability, costs and introduces additional safety concerns. To address these challenges, this study focused on intensifying CAR-T cell expansion using perfusion processes in xeno-free (XF) and serum-free (SF) culture medium. The impacts of alternative tangential flow (ATF) perfusion rates, perfusion start times and donor variability were evaluated using a Design of Experiments (DOE) approach in the Ambr ® 250 High-Throughput Perfusion stirred-tank bioreactor. This allowed the identification of optimal combinations of perfusion parameters on a per-donor basis, enabling 4.5-fold improvements in final cell yields and over 50% reductions in the expansion time required to reach a representative CAR-T dose compared to a fed-batch process. Subsequent process development then established an adaptive perfusion strategy enabling 130 ± 9.7-fold expansions to achieve final cell densities of 33.5 ± 3 × 10 6 cells/mL while reducing medium requirements by 11% without compromising CAR-T cell quality attributes compared to static well-plate cultures. Harvested cells predominantly expressed naïve and central memory markers, low levels of exhaustion markers, and maintained cytotoxicity and cytokine release in vitro . This study demonstrates the potential of optimising and adapting perfusion strategies in XF/SF-culture medium to enhance CAR-T cell yields, shorten expansion times and reduce medium consumption while addressing patient variability in clinical manufacturing. Key considerations for future implementation and improvement of adaptive perfusion feeds for clinical CAR-T manufacturing are also discussed
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Establishing a scalable perfusion strategy for the manufacture of CAR ‐T cells in stirred‐tank bioreactors using a quality‐by‐design approach
No full textChimeric antigen receptor T cell (CAR‐T) therapies show high remission rates for relapsed and refractory leukemia and lymphoma. However, manufacturing challenges hinder their commercial viability and patient accessibility. This study applied quality‐by‐design principles to identify perfusion critical process parameters for CAR‐T expansion in stirred tank bioreactors to maximize yields. A design of experiments in the Ambr® 250 High Throughput Perfusion small‐scale bioreactor revealed that earlier perfusion starts (48 h vs. 96 h post‐inoculation) and higher perfusion rates (1.0 VVD vs. 0.25 VVD) significantly increased cytotoxic CAR‐T cell yields without compromising critical quality attributes. Optimizing perfusion improved growth kinetics and yields across donor samples, achieving densities >21 × 10 6 cells/mL in 7 days, outperforming traditional fed‐batch and static flask cultures. This study underscores the importance of optimizing perfusion parameters to maximize CAR‐T yields and quality and highlights the utility of scale‐down models in reducing time, costs and risks associated with process development.Engineering and Physical Sciences Research Council https://doi.org/10.13039/50110000026
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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