scholarly journals Accelerating manufacturing to start large-scale supply of a new adenovirus-vectored vaccine within 100 days

2021 ◽  
Author(s):  
Carina CD Joe ◽  
Rameswara R Segireddy ◽  
Cathy Oliveira ◽  
Adam Berg ◽  
Yuanyuan Li ◽  
...  
Keyword(s):  
Production Process ◽  
Large Scale ◽  
Scale Up ◽  
Adenovirus Vector ◽  
Drug Substance ◽  
Economic Modelling ◽  
New Production ◽  
Bulk Drug ◽  
Vectored Vaccine ◽  
Manufacturing Network

The Coalition for Epidemic Preparedness Innovations &rsquo &lsquo 100-day moonshot &rsquo aspires to launch a new vaccine within 100 days of pathogen identification. Here, we describe work to optimize adenovirus vector manufacturing for rapid response, by minimizing time to clinical trial and first large-scale supply, and maximizing the output from the available manufacturing footprint. We describe a rapid viral seed expansion workflow that allows vaccine release to clinical trials within 60 days of antigen sequence identification, followed by vaccine release from globally distributed sites within a further 40 days. We also describe a new perfusion-based upstream production process, designed to maximize output while retaining simplicity and suitability for existing manufacturing facilities. This improves upstream volumetric productivity of ChAdOx1 nCoV-19 by around four-fold and remains compatible with the existing downstream process, yielding drug substance sufficient for 10000 doses from each liter of bioreactor capacity. Transition to a new production process across a large manufacturing network is a major task. In the short term, the rapid seed generation workflow could be used with the existing production process. We also use techno-economic modelling to show that, if linear scale-up were achieved, a single cleanroom containing two 2000 L bioreactors running our new perfusion-based process could supply bulk drug substance for around 120 million doses each month, costing <0.20 EUR/dose. We estimate that a manufacturing network with 32000 L of bioreactor capacity could release around 1 billion doses of a new vaccine within 130 days of genomic sequencing of a new pathogen, in a hypothetical surge campaign with suitable prior preparation and resources, including adequate fill-and-finish capacity. This accelerated manufacturing process, along with other advantages such as thermal stability, supports the ongoing value of adenovirus-vectored vaccines as a rapidly adaptable and deployable platform for emergency response.

scholarly journals A Novel Approach Using Conventional Methodologies to Scale up BNC Production Using Komagataeibacter medellinensis and Rotten Banana Waste as Alternative

Processes ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 1469
Author(s):  
Carlos Molina-Ramírez ◽  
Juan Álvarez ◽  
Robin Zuluaga ◽  
Cristina Castro ◽  
Piedad Gañán
Keyword(s):  
Production Process ◽  
Large Scale ◽  
Culture Medium ◽  
Scale Up ◽  
Glucose Consumption ◽  
Human Consumption ◽  
Scale Production ◽  
Bacterial Nanocellulose ◽  
Large Scale Production ◽  
Glucose Diffusion

Currently, cellulose nanostructures are among the most promising structures, and extensive work in materials and biotechnology industries is aimed at identifying an efficient process of production. Even when production at the laboratory scale is successful, crucial aspects of increased commercial applications for cellulose nanostructures are linked to large-scale production. Large-scale production requires a balance between the cost of the culture medium and product value. Therefore, in this work, for the optimization and scaling up of bacterial nanocellulose, a culture medium consisting of rotten banana unsuitable for human consumption was used for the first time as an inexpensive feedstock. Initially, the bacterial nanocellulose (BNC) culture medium conditions were optimized, and it was established that a glucose concentration of 26.4 g/L and a V/A ratio of 2.2 cm were the optimal conditions for production reaching a BNC yield of 5 g/L, which was 42.4% higher than the best result initially obtained. Finally, the scale-up process was performed, implementing a regime analysis methodology by comparing the characteristic times of the critical mechanisms involved in BNC production, namely, microbial growth, glucose consumption, BNC production, and glucose diffusion into the BNC membrane, as the first approach for this type of BNC production process. The mechanism underlying the BNC production process is glucose diffusion into the BNC membrane (characteristic time, 675.47 h). Thus, the V/A ratio was selected as the scale-up criterion most suitable for producing BNC under static culture conditions, allowing the production of 16 g of BNC after 12 d of fermentation in a plastic bioreactor, which was 3378% higher than that produced in glass vessels. The results obtained in this study may initiate further improvements in BNC commercial production by exploiting different feedstocks.

Solid Lipid Nanoparticles: A Promising Drug Delivery Technology

2009 ◽  
Vol 2 (2) ◽  
pp. 509-516
Author(s):  
S. Pragati ◽  
S. Kuldeep ◽  
S. Ashok ◽  
M. Satheesh
Keyword(s):  
Drug Delivery ◽  
Solid Lipid Nanoparticles ◽  
Large Scale ◽  
Colloidal Particles ◽  
Scale Up ◽  
Lipid Nanoparticles ◽  
Scale Production ◽  
Research Activity ◽  
New Approach ◽  
Solid Lipid

One of the situations in the treatment of disease is the delivery of efficacious medication of appropriate concentration to the site of action in a controlled and continual manner. Nanoparticle represents an important particulate carrier system, developed accordingly. Nanoparticles are solid colloidal particles ranging in size from 1 to 1000 nm and composed of macromolecular material. Nanoparticles could be polymeric or lipidic (SLNs). Industry estimates suggest that approximately 40% of lipophilic drug candidates fail due to solubility and formulation stability issues, prompting significant research activity in advanced lipophile delivery technologies. Solid lipid nanoparticle technology represents a promising new approach to lipophile drug delivery. Solid lipid nanoparticles (SLNs) are important advancement in this area. The bioacceptable and biodegradable nature of SLNs makes them less toxic as compared to polymeric nanoparticles. Supplemented with small size which prolongs the circulation time in blood, feasible scale up for large scale production and absence of burst effect makes them interesting candidates for study. In this present review this new approach is discussed in terms of their preparation, advantages, characterization and special features.

Recombinant Protein Production in Microalgae: Emerging Trends

2020 ◽  
Vol 27 (2) ◽  
pp. 105-110 ◽  
Author(s):  
Niaz Ahmad ◽  
Muhammad Aamer Mehmood ◽  
Sana Malik
Keyword(s):  
Chloroplast Genome ◽  
Recombinant Proteins ◽  
Large Scale ◽  
Higher Plants ◽  
Scale Up ◽  
Chloroplast Transformation ◽  
Point Of View ◽  
Nuclear Transformation ◽  
Scale Production ◽  
Algal Chloroplast

: In recent years, microalgae have emerged as an alternative platform for large-scale production of recombinant proteins for different commercial applications. As a production platform, it has several advantages, including rapid growth, easily scale up and ability to grow with or without the external carbon source. Genetic transformation of several species has been established. Of these, Chlamydomonas reinhardtii has become significantly attractive for its potential to express foreign proteins inexpensively. All its three genomes – nuclear, mitochondrial and chloroplastic – have been sequenced. As a result, a wealth of information about its genetic machinery, protein expression mechanism (transcription, translation and post-translational modifications) is available. Over the years, various molecular tools have been developed for the manipulation of all these genomes. Various studies show that the transformation of the chloroplast genome has several advantages over nuclear transformation from the biopharming point of view. According to a recent survey, over 100 recombinant proteins have been expressed in algal chloroplasts. However, the expression levels achieved in the algal chloroplast genome are generally lower compared to the chloroplasts of higher plants. Work is therefore needed to make the algal chloroplast transformation commercially competitive. In this review, we discuss some examples from the algal research, which could play their role in making algal chloroplast commercially successful.

Expanding the boundaries of learning

2021 ◽  
Vol 102 (8) ◽  
pp. 8-13
Author(s):  
Thomas Hatch
Keyword(s):  
Instructional Practices ◽  
New Hampshire ◽  
Large Scale ◽  
Educational Experiences ◽  
Scale Up ◽  
Project Based Learning

Taking advantage of the possibilities for learning outside of school requires us to build on what we know about why it is so hard to sustain and scale up unconventional educational experiences within conventional schools. To illustrate the opportunities and challenges, Thomas Hatch describes a large-scale approach to project-based learning developed in a camp in New Hampshire and incorporated in a Brooklyn school, a trip-based program in Detroit, and Singapore’s systemic embrace of learning outside school. By understanding the conditions that can sustain alternative instructional practices, educators can find places to challenge the boundaries of schooling and create visions of the possible that exceed current constraints.

scholarly journals Scaling Up Delivery of Biofortified Staple Food Crops Globally: Paths to Nourishing Millions

2021 ◽  
pp. 037957212098250
Author(s):  
Jennifer K. Foley ◽  
Kristina D. Michaux ◽  
Bho Mudyahoto ◽  
Laira Kyazike ◽  
Binu Cherian ◽  
...  
Keyword(s):  
Pearl Millet ◽  
Large Scale ◽  
Scale Up ◽  
Lessons Learned ◽  
Raw Material ◽  
Micronutrient Deficiencies ◽  
Seed Systems ◽  
Public And Private ◽  
Context Specific ◽  
Public And Private Sector

Background: Micronutrient deficiencies affect over one quarter of the world’s population. Biofortification is an evidence-based nutrition strategy that addresses some of the most common and preventable global micronutrient gaps and can help improve the health of millions of people. Since 2013, HarvestPlus and a consortium of collaborators have made impressive progress in the enrichment of staple crops with essential micronutrients through conventional plant breeding. Objective: To review and highlight lessons learned from multiple large-scale delivery strategies used by HarvestPlus to scale up biofortification across different country and crop contexts. Results: India has strong public and private sector pearl millet breeding programs and a robust commercial seed sector. To scale-up pearl millet, HarvestPlus established partnerships with public and private seed companies, which facilitated the rapid commercialization of products and engagement of farmers in delivery activities. In Nigeria, HarvestPlus stimulated the initial acceptance and popularization of vitamin A cassava using a host of creative approaches, including “crowding in” delivery partners, innovative promotional programs, and development of intermediate raw material for industry and novel food products. In Uganda, orange sweet potato (OSP) is a traditional subsistence crop. Due to this, and the lack of formal seed systems and markets, HarvestPlus established a network of partnerships with community-based nongovernmental organizations and vine multipliers to popularize and scale-up delivery of OSP. Conclusions: Impact of biofortification ultimately depends on the development of sustainable markets for biofortified seeds and products. Results illustrate the need for context-specific, innovative solutions to promote widespread adoption.

The Research of Production Process Statistical Steady-State Based on the Hypothesis Test

2011 ◽  
Vol 314-316 ◽  
pp. 2433-2438
Author(s):  
Wei Zhi Wang
Keyword(s):  
Quality Control ◽  
Steady State ◽  
Production Process ◽  
Quantitative Method ◽  
Large Scale ◽  
Hypothesis Test ◽  
Influence Factors ◽  
Normal Operation ◽  
Scale Production ◽  
Large Scale Production

By only applying a after the event exam in the quality control of the batch production is not enough to meet the needs of modern large-scale production. To a certain extent, modern quality control is a dynamic process of the steady-state judge and adjustment. A simple and reliable steady-state judge rule and method is the premise to guarantee the normal operation. This paper provides a quantitative method to evaluate production process steady-state by analyzing influence factors based on mathematical statistics. The method is both suitable for simple production process and complex production process with sub-processes.

scholarly journals Direct detection of SARS-CoV-2 using non-commercial RT-LAMP reagents on heat-inactivated samples

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alisa Alekseenko ◽  
Donal Barrett ◽  
Yerma Pareja-Sanchez ◽  
Rebecca J. Howard ◽  
Emilia Strandback ◽  
...  
Keyword(s):  
Large Scale ◽  
Direct Detection ◽  
Dna Polymerases ◽  
Scale Up ◽  
Lamp Assay ◽  
Cost Effective ◽  
Reaction Conditions ◽  
Clinical Patient ◽  
Reverse Transcriptases ◽  
Large Scale Testing

AbstractRT-LAMP detection of SARS-CoV-2 has been shown to be a valuable approach to scale up COVID-19 diagnostics and thus contribute to limiting the spread of the disease. Here we present the optimization of highly cost-effective in-house produced enzymes, and we benchmark their performance against commercial alternatives. We explore the compatibility between multiple DNA polymerases with high strand-displacement activity and thermostable reverse transcriptases required for RT-LAMP. We optimize reaction conditions and demonstrate their applicability using both synthetic RNA and clinical patient samples. Finally, we validate the optimized RT-LAMP assay for the detection of SARS-CoV-2 in unextracted heat-inactivated nasopharyngeal samples from 184 patients. We anticipate that optimized and affordable reagents for RT-LAMP will facilitate the expansion of SARS-CoV-2 testing globally, especially in sites and settings where the need for large scale testing cannot be met by commercial alternatives.

scholarly journals Mechanical Properties of Protective Coatings against Marine Fouling: A Review

Polymers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 173
Author(s):  
Alessandro Pistone ◽  
Cristina Scolaro ◽  
Annamaria Visco
Keyword(s):  
Mechanical Properties ◽  
Large Scale ◽  
Protective Coatings ◽  
Scale Up ◽  
Product Distribution ◽  
Properties Of Coatings ◽  
Fouling Organism ◽  
Ship Hulls ◽  
Marine Industry ◽  
Application Fields

The accumulation of marine organisms on ship hulls, such as microorganisms, barnacles, and seaweeds, represents a global problem for maritime industries, with both economic and environmental costs. The use of biocide-containing paints poses a serious threat to marine ecosystems, affecting both target and non-target organisms driving science and technology towards non-biocidal solutions based on physico-chemical and materials properties of coatings. The review reports recent development of hydrophobic protective coatings in terms of mechanical properties, correlated with the wet ability features. The attention is focused mainly on coatings based on siloxane and epoxy resin due to the wide application fields of such systems in the marine industry. Polyurethane and other systems have been considered as well. These coatings for anti-fouling applications needs to be both long-term mechanically stable, perfectly adherent with the metallic/composite substrate, and capable to detach/destroy the fouling organism. Prospects should focus on developing even “greener” antifouling coatings solutions. These coatings should also be readily addressable to industrial scale-up for large-scale product distribution, possibly at a reasonable cost.

scholarly journals Foaming of rhamnolipids fermentation: impact factors and fermentation strategies

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhijin Gong ◽  
Ge Yang ◽  
Chengchuan Che ◽  
Jinfeng Liu ◽  
Meiru Si ◽  
...  
Keyword(s):  
Production Process ◽  
Large Scale ◽  
Commercial Production ◽  
Impact Factors ◽  
Scale Production ◽  
Large Scale Production ◽  
Foaming Behavior ◽  
Production Strategies ◽  
Potential Applications ◽  
And Control

AbstractRhamnolipids have recently attracted considerable attentions because of their excellent biosurfactant performance and potential applications in agriculture, environment, biomedicine, etc., but severe foaming causes the high cost of production, restraining their commercial production and applications. To reduce or eliminate the foaming, numerous explorations have been focused on foaming factors and fermentation strategies, but a systematic summary and discussion are still lacking. Additionally, although these studies have not broken through the bottleneck of foaming, they are conducive to understanding the foaming mechanism and developing more effective rhamnolipids production strategies. Therefore, this review focuses on the effects of fermentation components and control conditions on foaming behavior and fermentation strategies responded to the severe foaming in rhamnolipids fermentation and systematically summarizes 6 impact factors and 9 fermentation strategies. Furthermore, the potentialities of 9 fermentation strategies for large-scale production are discussed and some further strategies are suggested. We hope this review can further facilitate the understanding of foaming factors and fermentation strategies as well as conducive to developing the more effective large-scale production strategies to accelerate the commercial production process of rhamnolipids.

Sign in / Sign up

Export Citation Format

Share Document