Is this you? As a journalist, you can create a free Muck Rack account to customize your profile, list your contact preferences, and upload a portfolio of your best work.
Claim your profile
Articles by Development Merck
Establishing a Robust High Performance Liquid Chromatography−Ultraviolet Detection Technique for Nitrite Quantification in Pharmaceutical Excipients and Active Pharmaceutical Ingredients
Conflicts of Interest The authors declare no conflicts of interest. Data Availability Statement The data that support the findings of this study are available from the corresponding author upon reasonable request. Supporting Information Filename Description jssc70512-sup-0001-SuppMat.docx601.3 KB Supporting File: jssc70512-sup-0001-SuppMat.docx.
Metabolic Flux Analysis Reveals Cell Line-Specific Rewiring in CHO Cells Following TCA Cycle Intermediate Feeding for Bioprocess pH Control
1 Introduction The therapeutic protein market has experienced remarkable growth since the introduction of the first commercially available recombinant DNA product over 35 years ago. In 2021, the industry reached a significant milestone with the approval of the 100th antibody by the FDA, which reflects the increasing popularity of therapeutic protein products with newer modalities entering diverse fields for diagnostics and treatments.
Characterization of apoptosis in fed‐batch cultures highlights the impact of timely process intervention on improving recombinant protein productivity
CONFLICT OF INTEREST STATEMENT The authors declare no conflict of interest. DATA AVAILABILITY STATEMENT The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
TCEP‐Mediated Protein Hydrolysis: Highly Selective Cleavage C‐Terminal to Aspartic Acid
Conflicts of Interest The authors declare the following competing financial interest: All authors were employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD) at the time the work was conducted, as contractors or full time employees. All funding was done by MSD. Data Availability Statement The data that support the findings of this study are available from the corresponding author upon reasonable request.
Enhancing mRNA vaccine production: Optimization of in vitro transcription for improved yield and purity
CONFLICT OF INTEREST STATEMENT The authors: Kaixi Zhao, Jessica Raffaele, David A. Holland, Kristen Feibelman, Jon Shanter, and Emily Wen are employees of Merck & Co., Inc. and may own stock or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. Kathleen Lengel is an employee of Eurofins PSS Insourcing Solutions. This could suggest a potential competing interest. However, they affirm that this has not affected the objectivity of the data and results, or research integrity in this paper.
Optimizing sterile filtration of nanoemulsions through proper choice of prefilter properties
1 INTRODUCTION Nanoemulsions (NEs) are stable dispersions formed by mixing oil and water phases with surfactants to form a kinetically stabilized emulsion with droplets <1 μm in size.
Overexpression of Matriptase‐1 Inhibitor HAI‐1 as an Effective Strategy to Reduce Proteolytic Clipping in Chinese Hamster Ovary Cells
Overexpression of Matriptase‐1 Inhibitor HAI‐1 as an Effective Strategy to Reduce Proteolytic Clipping in Chinese Hamster Ovary Cells
Sialylation Impacts Separation of a Biotherapeutic by Capillary Gel Electrophoresis
Conflicts of Interest The authors declare no conflicts of interest. Supporting Information Filename Description elps70006-sup-0001-SuppMat.docx2.5 MB Supporting Information file 1:elps70006-sup-0001-SuppMat.docx elps70006-sup-0002-FigureS1-FigureS15.zip1.8 MB Supporting Information file 2:elps70006-sup-0002-FigureS1–FigureS15.zip References 1, , and , “Recent Advances in Microscale Separation Techniques for Glycome Analysis,” Journal of Separation Science 47 (2024): 2400170.
Minimizing batch‐to‐batch variability of a live virus vaccine by process analytical technologies
ANOVA analysis of variance CHO Chinese hamster ovary Cp capacitance CVA21 coxsackievirus A21 DF degrees of freedom DO dissolved oxygen DPI days post infection ED50 effective dose 50% EMEM eagle's minimum essential media FDA food and drug administration FTIR fourier-transform infrared spectroscopy MOI multiplicity of infection MRC5 medical research council cell strain 5 OPC open platform communication OUR oxygen uptake rate PAT process analytical technology SK-MEL-28 human melanoma cell line...
CRISPR‐Editing of the Vero Cell Line Improves Processability of Live Virus Vaccines by Enabling Targeted Proteolysis of Fibronectin
Supporting Information Filename Description bit29028-sup-0001-TEVVero_Supplemental_Information_revised.docx1.1 MB TEVVero Supplemental Information (revised). References , , , and . 2023. “Purification of Recombinant Vesicular Stomatitis Virus-Based HIV Vaccine Candidate.” Vaccine 41, no. 13: 2198–2207. , , , and . 2009. “Vero Cell Platform in Vaccine Production: Moving Towards Cell Culture-Based Viral Vaccines.” Expert Review of Vaccines 8, no. 5: 607–618. , , and . 2016.
Enhanced cell‐specific productivity through delayed supplementation of antioxidants in intensified processes
CONFLICT OF INTEREST STATEMENT Declarations of interest: none. Supporting Information Filename Description btpr70036-sup-0001-supinfo.docxWord 2007 document , 416.8 KB Data S1. Supporting Information. REFERENCES 1, . Biopharmaceutical benchmarks 2022. Nat Biotechnol. 2022; 40(12): 1722-1760. 2, , , , , . Improving the efficiency of CHO cell line generation using glutamine synthetase gene knockout cells. Biotechnol Bioeng. 2012; 109(4): 1007-1015. 3, , , , .
Systematic Investigation of Impact of Antifoam and Extracellular Vesicles on Fouling of Hollow Fiber Filters in Intensified Perfusion Processes Highlights the Key Impact of Antifoam
1 Introduction High cell density perfusion cultures using CHO cells are increasingly adopted for biologics manufacturing (Karst et al. 2018; Wong et al. 2022; Gagnon et al. 2018). Intensified perfusion processes typically have higher volumetric productivities that enables operating in smaller and more flexible manufacturing facilities (Pollock et al. 2013).
Next‐Generation Sequencing‐Based In Silico Transgene Integration Profiling Tool Accelerates Cell Line Genetic Characterizations
Conflicts of Interest The authors declare no conflicts of interest. Supporting Information Filename Description biot202400675-sup-0001-SuppMat.docx1.3 MB Supporting information biot202400675-sup-0002-SuppMat.xlsx114.2 KB Supporting information References 1, , , , , and , “Efficient Transposition of the PiggyBac (PB) Transposon in Mammalian Cells and Mice,” Cell 122, no. 3 (2005): 473–483.
Assessing Classification Models of Pharmaceuticals With Conformal Prediction
Conflicts of Interest The authors declare no conflicts of interest. References 1 and , “Partial Least Squares Discriminant Analysis: Taking the Magic Away,” Journal of Chemometrics 28, no. 4 (2014): 213–225, https://doi.org/10.1002/cem.2609. 2, , and , “Partial Least Squares-Discriminant Analysis (PLS-DA) for Classification of High-Dimensional (HD) Data: A Review of Contemporary Practice Strategies and Knowledge Gaps,” Analyst 143, no. 15 (2018): 3526–3539, https://doi.org/10.1039/C8AN00599K.
Enhancing real‐time cell culture process monitoring through the integration of advanced machine learning techniques: A comparative analysis of Raman and capacitance spectroscopies
CONFLICT OF INTEREST STATEMENT The authors declare no conflict of interest. Supporting Information Filename Description btpr70013-sup-0001-Supporting_Materials.docxWord 2007 document , 82.4 KB Data S1: Supporting Information. REFERENCES 1, , , , , . Industry 4.0 for pharmaceutical manufacturing: preparing for the smart factories of the future. Int J Pharm. 2021; 602:120554. 2, . The importance of process intensification and PAT for achieving real-time release. BioPharm Int. 2021; 34(1): 31-33. 3.
Rapid bioreactor process optimization and scale‐up for production of a measles vector COVID‐19 vaccine candidate
CONFLICT OF INTEREST STATEMENT The authors declare the following financial interest/personal relationships, which may be considered a potential competing interest. All coauthors are current or former employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may own stock or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. All research activities described in this publication were funded by Merck & Co., Inc., Rahway, NJ, USA. REFERENCES 1.
Coupling high‐throughput and modeling approaches to streamline early‐stage process development for biologics
CONFLICT OF INTEREST STATEMENT The authors declare no conflict of interest. REFERENCES 1, , , , . Monoclonal antibody therapies for COVID-19: lessons learned and implications for the development of future products. Curr Opin Biotechnol. 2022; 78:102798. doi:10.1016/j.copbio.2022.102798 2, , , et al. How to improve R&D productivity: the pharmaceutical industry's grand challenge. Nat Rev Drug Discov. 2010; 9(3): 203-214. doi:10.1038/nrd3078 3, , , .
Proteomics Reveals Distinctive Host Cell Protein Expression Patterns in Fed‐Batch and Perfusion Cell Culture Processes
1 Introduction Recombinant proteins including monoclonal antibodies (mAbs) stand at the forefront of therapeutic protein development within the biopharmaceutical industry, offering targeted treatments for a diverse array of diseases. Integral to their production are Chinese hamster ovary (CHO) cells, which have solidified their position as the preferred host organism [1].
Enzyme purification and sustained enzyme activity for pharmaceutical biocatalysis by fusion with phase‐separating intrinsically disordered protein
1 INTRODUCTION An increasing number of enzymes have been discovered and engineered thanks to modern genomics and proteomics. This has enabled enzymes to be applied in many fields for in vitro biocatalysis, including the chemical, food, and materials industries (Ismail & Nielsen, 2010; Kannan et al., 2023; Kirk et al., 2002). In particular, biocatalysis is increasingly prominent in the pharmaceutical industry (Griengl et al., 2000; Hills, 2003; McIntosh & Benkovics, Silverman, et al., 2021).
Detection of residual T7 RNA polymerase used in mRNA in vitro transcription by Simple Western
FT flow through IVT in vitro transcription LNPs lipid nanoparticles mRNA messenger RNA MW molecular weight NTPs RNA nucleotides pDNA plasmid DNA SW Simple Western T7 RNAP T7 RNA polymerase TFF tangential flow filtration Compared to traditional vaccines, advantages of messenger RNA (mRNA) vaccines include simple design, fast development, and platformed manufacture [1].
High‐throughput in silico workflow for optimization and characterization of multimodal chromatographic processes
Corresponding Author Steven M. Cramer Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York, USA Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, USA Correspondence Steven M. Cramer, Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY, USA.
Combining descriptive and predictive modeling to systematically design depth filtration‐based harvest processes for biologics
CONFLICT OF INTEREST STATEMENT The authors declare that there are no conflicts of interest for this work. Supporting Information REFERENCES , , , , , , , & (2022). Chromatographic capture of cells to achieve single stage clarification in recombinant protein purification. Biotechnology Progress, 38(2), e3227. https://doi.org/10.1002/btpr.3227 , , & (2006). Combined models of membrane fouling: Development and application to microfiltration and ultrafiltration of biological fluids.
Unprecedented Packing Polymorphism of Oxindole: An Exploration Inspired by Crystal Structure Prediction
Supporting Information As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.
Evaluation of various membranes at different fluxes to enable large‐volume single‐use perfusion bioreactors
CONFLICT OF INTEREST STATEMENT The authors have no conflict of interest. Supporting Information Filename Description bit28722-sup-0001-Supplementary_Material.docx132.3 KB Supporting information. REFERENCES , , & (2020). Trends in FDA drug approvals over last 2 decades: An observational study. Journal of Family Medicine and Primary Care, 9, 105–114. , , , & (2016). Ultrafiltration of highly concentrated antibody solutions: Experiments and modeling for the effects of module and buffer conditions.
Formation, Selective Encapsulation, and Tautomerization Control of Isoindolone Utilizing Guanidinium Sulfonate Frameworks
Conflict of interests The authors declare no conflict of interest. Supporting Information As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.
Robust platform for inline Raman monitoring and control of perfusion cell culture
CONFLICT OF INTEREST STATEMENT The authors declare no conflict of interest. Supporting Information Filename Description bit28680-sup-0001-supplementary_information.docx352.1 KB Supporting information. REFERENCES , , , , , , , & (2011). Real time monitoring of multiple parameters in mammalian cell culture bioreactors using an in-line Raman spectroscopy probe. Biotechnology and Bioengineering, 108(5), 1215–1221. https://doi.org/10.1002/bit.23023 , , , , , & (2015).
Engineering Hydroxylase Activity, Selectivity, and Stability for a Scalable Concise Synthesis of a Key Intermediate to Belzutifan
Conflict of interest The authors disclose that some authors are inventors on unpublished patent applications assigned to Merck Sharp and Dohme LLC, Rahway, NJ, USA related to the work described in this manuscript. Supporting Information As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset.
Adaptation of an rVSV Ebola vaccine purification process for rapid development of a viral vaccine candidate for SARS‐CoV‐2
CONFLICT OF INTEREST STATEMENT All authors are/were employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may potentially own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. REFERENCES 1 World Health Organization. (2022). Covid-19 vaccine tracker and landscape. World Health Organization. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines 2, , , & (2020).
Front Cover Picture: Copper‐Enabled Photo‐Sulfonylation of Aryl Halides Using Alkylsulfinates (Adv. Synth. Catal. 22/2023)
Graphical Abstract The front cover illustrates a copper-enabled, regioselective photo-sulfonylation of polyhalogenated arenes using alkylsulfinate salts, which is compared to results using thermal conditions. The photochemical method can provide advantages with regards to safety and the source of starting material (e. g., aryl chlorides are suitable substrates in addition to aryl bromides). Details can be found in the Research Article by Lehnherr, Lam, and co-workers (V. Mdluli, D. Lehnherr, Y.-h.
Glass microspargers as effective frit spargers in single use bioreactors
CONFLICT OF INTEREST STATEMENT The authors declare no conflicts of interest. REFERENCES 1, , , . Influence of surface wettability on microbubble formation. Langmuir. 2016; 32: 1269-1278. doi:10.1021/acs.langmuir.5b03743 2. Single-use in the biopharmaceutical industry: a review of current technology impact, challenges and limitations. Food Bioprod Process. 2015; 93: 98-114. doi:10.1016/j.fbp.2013.12.002 3, .
Deep learning image analysis models pretrained on daily objects are useful for the preliminary characterization of particulate pharmaceutical samples
Abstract Visible and subvisible particles are a quality attribute in sterile pharmaceutical samples. A common method for characterizing and quantifying pharmaceutical samples containing particulates is imaging many individual particles using high-throughput instrumentation and analyzing the populations data. The analysis includes conventional metrics such as the particle size distribution but can be more sophisticated by interpreting other visual/morphological features.
Purification processes of live virus vaccine candidates expressed in adherent Vero cell lines via multimodal chromatography in flowthrough mode
1 INTRODUCTION The emergence of recombinant virus vectors as a platform for viral vaccines, due to the expression of heterologous viral proteins on their surface, has led to an increased focus on live virus vaccines (LVVs) (Travieso et al., 2022). Recently, a chimeric SARS-CoV-2 vaccine candidate, VSV∆G-SARS-CoV-2, was developed by replacing the live vesicular stomatitis virus glycoprotein gene with a coding sequence for the SARS-CoV-2 spike glycoprotein (Espeseth et al., 2022).
Purification processes of live virus vaccine candidates expressed in adherent Vero cell lines via multimodal chromatography in flowthrough mode
Impact of FN on Measles purification It was desired to understand the impact of FN on the purification train, and specifically the UF/DF step, during processing of Measles generated in the adherent Vero cell culture system. The ability of Capto MMC ImpRes to effectively remove FN allowed for the generation of a largely FN-free CP.
Protein adsorption on core‐shell resins for flow‐through purifications: Effect of protein molecular size, shape, and salt concentration
2.2 Method 2.2.1 Synthesis of PEGylated BSA PEGylated BSA with 10 and 30 kDa PEG were synthesized as previously described.38 Briefly, 10 or 30 kDa methoxy PEG maleimide were added to solutions containing 10 mg/ml BSA monomer in a 20 mM BTP-HCl buffer at pH 7.0 in a 1:1 molar ratio and mixed gently for 24 h.
Determination of protein concentration in downstream biomanufacturing processes by in‐line index of refraction
1 INTRODUCTION In recent years biotechnology companies have been addressing the implementation of process analytical technology (PAT) and chemometrics in biomanufacturing.1-3 Advanced technologies utilizing probes and sensors capable of real-time monitoring and analysis have contributed significantly toward implementation of PAT in GMP production.4 A cornerstone of this progress has been the development of monitoring capabilities incorporated into the bioprocess by moving from off-line...
Identification and Characterization of a Residual Host Cell Protein Hexosaminidase B Associated with N‐glycan Degradation During the Stability Study of a Therapeutic Recombinant Monoclonal Antibody Product
RESEARCH ARTICLE Xuanwen Li Corresponding Author xuanwen.li@merck.com orcid.org/0000-0001-7548-583X Analytical Research & Development Mass Spectrometry, Merck & Co., Inc., Kenilworth, NJ, USA Correspondence Email: xuanwen.li@merck.com Contribution: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Visualization, Writing - original draft, Writing - review & editing Search for more papers by this author This article has been accepted for publication and undergone...
Effectiveness of Host Cell Protein Removal using Depth Filtration with a Filter Containing Diatomaceous Earth
RESEARCH ARTICLE Andrew L. Zydney Corresponding Author E-mail address: zydney@engr.psu.edu https://orcid.org/0000-0003-1865-9156 Department of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania, USA Correspondence Andrew L. Zydney, 404 Chemical & Biomedical Engineering Bldg, The Pennsylvania State University, University Park, PA 16802.
Show More
loading
Actions
Is this you?
As a journalist, you can create a free Muck Rack account to customize your profile, list your contact preferences, and upload a portfolio of your best work.Get in touch with Development
Contact Development, search articles and posts on X, monitor coverage, and track replies from one place.
Learn more about Muck Rack