Large-scale Manufacturing Facility Research Articles

Lipid-Based Nanocarriers in the Management of Pulmonary Complications in Cystic Fibrosis

Abstract:: Code 35, the cystic fibrosis transmembrane conductance regulator (CFTR) causes respiratory failure, inflammation, and decreased airway mucociliary clearance. The absence of trustworthy preclinical models that replicate the anatomical, immunological, and bioelectrical characteristics of human CF lungs restricts the discovery of new therapies for the disease. Alternative carriers to liposomes, polymeric nanoparticles, and inorganic carriers include lipid-based nanocarriers (LBCs). Delivering medicines, nucleic acids, proteins, peptides, nutraceuticals, and cosmetics via LBCs has received more and more attention in recent years. Due to their simple production, physicochemical stability, and scalability, these nanocarriers have caught the attention of the industrial sector. Because of these qualities, LBCs are well suited for industrial manufacturing. Clinical trials are already being conducted on a number of LBC-containing items and are likely to swiftly grow in popularity. For commercial applications to produce enough formulations for clinical research, a large-scale manufacturing facility is necessary. The mainstay of treatment for CF, asthma, and chronic obstructive lung disease is the inhalation of corticosteroids and topical bronchodilators. These drugs are given through a metered-dose inhaler (MDI), a dry powder inhaler (DPI), a jet, or an ultrasonic nebulizer. Although the sheer number of gadgets may be overwhelming for patients and doctors, each has unique benefits.

Utilizing of Digital Printing Techniques to Create Customize Designs for Textile Floor Covering

Industry researchers estimate that the global Textile covering flooring market size was estimated at USD 84.49 billion in 2018 and expected to register a CAGR of 3.2% from 2020 to 2025. Rising demand for carpet tiles on account of availability in a range of colors, patters, and textures is expected to drive the growth. Textile covering flooring manufacturers are involved into production of different products including carpets and area rugs which such as roll goods, carpet tiles, bath mates, and broadlooms among others. Carpet tiles and broadloom are the majorly used Textile covering floorings on account of superior attributes, such as flexibility and dimensional stability. While tufting covering floor about 90% share of this volume, and 7% needle punch covering floor 50% of tufting and needle punch covering floor printed.    While digital printing currently amounts to about 2% share of this volume, digital printing continues to expand with the movement from mass-production to mass customization of printed goods.  Offset/gravure to inkjet/laser printing technology, digital carpet printing offers new creative possibilities for printing over traditional screen-printing. As a result, digital printing enables a shift from printing in large scale manufacturing facilities to smaller cottage businesses focusing on specialty printing Applications. In today’s digital technology age, there is greater demand for better technology and faster turnaround cycles in terms of mass production, mass customization and cost effectiveness for the textile, apparel and printing sectors, and will be in carpet also. (THE FUTURE OF PRINTING @ ITMA 2019). Some reasons for why digital printed is suitable for carpet customize. Short run printing advantage: Digital Textile floor covering printing efficiently produces designs at run lengths as low as one yard of carpet without the need for screen changes. Lower water and power consumption: Digital Textile floor covering printing eliminates the substantial amount of water and electrical energy one requires for rotary screen or chromo jet preparation, printing and cleanup. Even greater water and power savings can be achieved with disperse/sublimation and pigment Digital Textile floor covering inks, which only require a heat-fixation step for post treatment. Less chemical waste: Digital Textile floor covering printing results in significantly less ink usage and waste Relative to screen and chromo jet -printing. Taking into account the additional chemistry and chemical waste from Screen production, printing digitally offers a greener advantage for printing. Large repeat sizes: Digital textile printers can print large designs (e.g. cartoon characters on Runners and Area Rug) on roll wall to wall carpet without the usual rotary screen-printing limitation in pattern repeat size. Reduced production space requirements: By not having to prepare and store customer screens for future use, the production footprint for digital printing is a fraction of the size one requires for a rotary screen print facility. Less printed inventory needed: Digital Textile floor covering printing permits the option to print a design at will. This means that manufacturers with an integrated digital printing system in their production chain can keep a stock of unprinted textiles on hand to print as required. This reduces the need for pre-printed inventory of Textile floor covering that may or may not be used. Sampling and production done on same printer: By being able to print samples (strike-offs) on the same printer one uses for production, digital Textile floor covering print shops can present their customers with proof samples of designs that will exactly match the final printed material. Print flexibility: Printing houses utilizing all-digital, chromo jet and screen technologies can choose to print a small quantity of designs with different color combinations (colorways) first with their digital Textile floor covering printing solutions for test the market. They can later opt to print higher volumes of the most desired color designs using chromo jet or rotary screen technology. Variety of creative design choices for printing: Digital Textile floor covering printing provides the option to print photographic/continuous tone images, spot color pattern designs or a combination of both. This expands the creative printing alternatives for carpet and interior designers. Low capital investment: The relatively low capital investment to setup a digital Textile floor covering print shop, especially compared to rotary screen-printing production, makes it possible to start small and expand as business grows special in scatter rug, bath mat and tiles. The research deals with the following axes: Definition of digital printing and its uses. Comparison between traditional and digital printing methods Conducting many technical experiments of digital printing on different types of textile floor covering. The use of digital printing of textile floor covering in the field of small industries

A case-study in the introduction of a digital twin in a large-scale smart manufacturing facility

In the field of industrial engineering the knowledge produced by newly obtained data is driving business forward. Automating the process of capturing data from industrial machines, analyzing it and using the knowledge gained to make better decisions for the machines is the crux of the digital twin. Sensor technology, Internet of Things platforms, information and communication technology and smart analytics allow the digital twin to transform a physical asset into a connected smart item that is now part of a cyber physical system and that is far more valuable than when it existed in isolation. The digital twin can be adopted by the maintenance engineering industry to aid in the prediction of issues before they occur thus creating value for the business. In this paper the authors look to introduce a maintenance digital twin to a large-scale manufacturing facility. Issues that hamper such work are discovered and categorized to highlight the difficulty of the practical installation of this concept. To aid in the installation process a digital twin framework is presented that simplifies the digital twin development process into steps that can be completed independently. With the framework in place the authors commence the task of completing these steps.

PHP62 - HOME BREWED AUTOLOGOUS THERAPIES: CAN BIOPHARMA WIN THE WAR WITH DOMESTIC AUTOLOGOUS CELL & GENE THERAPY MANUFACTURERS?

Governments in many countries (e.g. UK and Canada) are investing in developing cell and gene therapy (CGT) R&D, manufacturing, and commercialisation capabilities. Associated economic incentives to stimulate local job creation is a primary driver and keeping innovation in-house is a secondary driver. The objective of this study is to analyse the strengths and weaknesses of government-sanctioned manufacturing of autologous CGTs versus traditional manufacturing models used by Biopharma. A detailed review of publications, government policies and investment practices was conducted to highlight existing and future plans for enabling domestic manufacturing. An evaluation of the pros and cons of domestic CGT manufacturing was also conducted. Domestic manufacturing of autologous CGTs offers several advantages over traditional manufacturing models used by Biopharma. Key strengths include: Democratisation of development, localisation of supply by leveraging the use of existing healthcare infrastructure, improved logistics and flexibility in responding to local patient demand, and lower cost to the healthcare system. Major drivers are the preferential regulatory and/or reimbursement pathways for domestic products. However, there are important weaknesses that will need to be addressed to displace Biopharma manufactures. These include lack of consistency in manufacturing quality for autologous therapies globally and the infrastructure required to gather real world evidence on safety and long-term efficacy for CGT products. Access to CGTs has become a staple item on the national agenda for many countries. Governments are starting to invest in large-scale manufacturing facilities, and more countries are likely to join the race. Given the different strengths on both sides, this creates an opportunity for collaboration between domestic manufacturers and Biopharma to develop a steady path forward and ensure patients have access to these transformative therapies.

What’s in a face? Making sense of tangible information systems in terms of Peircean semiotics

Within this paper, we utilise a delimited area of philosophy to help make sense of a delimited area of design science as it pertains to a class of contemporary information systems. The philosophy is taken from that of Charles Sanders Peirce; the design science is directed at the construction of visual devices in that area known as visual management. The utilisation of such devices within their wider visual management systems we take to be instances of what we refer to as tangible information systems. Tangible information systems use tangible artefacts, such as whiteboards and magnetic tokens, to accomplish information. We particularly use Peircean semiotics to analyse the use of tangible emoticons articulated upon performance boards within a large-scale manufacturing facility. We infer from our analysis of these informative artefacts that certain integrated aspects of Peircean philosophy offers an alternative way of framing notions of a proper design science, design theory, and design artefact for the discipline of information systems.

China’s BeiGene plans biologics plant

Beijing-based oncology drug discovery firm BeiGene is joining with the government of Guangzhou in southern China to build a $330 million biologic drug facility in the Guangzhou Development District. The venture will also fund biologic drug R&D in China. Under the agreement, $30 million will come from BeiGene and $150 million from Guangzhou. The venture will borrow the rest. BeiGene says it needs large-scale manufacturing facilities to ensure growth.

Functionalization of cellulose nanocrystals for advanced applications

Replacing the widespread use of petroleum-derived non-biodegradable materials with green and sustainable materials is a pressing challenge that is gaining increasing attention by the scientific community. One such system is cellulose nanocrystal (CNC) derived from acid hydrolysis of cellulosic materials, such as plants, tunicates and agriculture biomass. The utilization of colloidal CNCs can aid in the reduction of carbon dioxide that is responsible for global warming and climate change. CNCs are excellent candidates for the design and development of functional nanomaterials in many applications due to several attractive features, such as high surface area, hydroxyl groups for functionalization, colloidal stability, low toxicity, chirality and mechanical strength. Several large scale manufacturing facilities have been commissioned to produce CNCs of up to 1000kg/day, and this has generated increasing interests in both academic and industrial laboratories. In this feature article, we will describe the recent development of functionalized cellulose nanocrystals for several important applications in ours and other laboratories. We will highlight some challenges and offer perspectives on the potentials of these sustainable nanomaterials.

34 - Transcriptome and Secretome Based Assay Matrix to Define Mesenchymal Stromal Cell Immune Potency

in this large scale manufacturing facility were similar to at the academic facility. Leveraging a proven step-wise industry transfer process to capture academic experience along with extensive collaborative training and strong analytics led to this successful CAR cell therapy process transfer from academia to industry. This resulted in comparable CTL019 cell expansion growth curves to those observed from academia. Cell processing for the Phase II trials initiated outside the US, including Europe, Canada and Australia, is carried out at the state-of-the-art global manufacturing facility. (Figure 1)

Successful Translation of Chimeric Antigen Receptor (CAR) Targeting CD19 (CTL019) Cell Processing Technology from Academia to Industry

Introduction: Use of chimeric Antigen Receptor (CAR) targeting CD19 (CTL019) as a cell-based immunotherapy has been reported to have positive results with high complete response rates in hematological malignancies, including relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphomas (NHL). In all the studies reported thus far with CTL019, the cell therapy was processed in an academic center (University of Pennsylvania). For large-scale manufacturing of CTL019 and more widespread distribution to patients and physicians, a focus on scalability to meet demands is critical. Here we report the outcomes from successful transfer of CTL019 processing technology from academia to our large-scale GMP facility.Methods & Results: The focus of effective transfer included areas of manufacturing process and analytical technology to consistently manufacture CTL019 with scale-up capabilities. Through strong collaboration of diverse technology transfer team participants from academia, GMP production, Technical development, Quality Assurance and Regulatory, we developed a step-based approach for process transfer. After gathering data from the academia process we made improvements to further enhance control and consistency of the process by implementing key Quality Systems elements (e.g., batch record, change control, process SOPs). Areas of improvement included closing of process steps through customized consumable and equipment solutions; replacing some manual processes with automation solutions and developing a new quantitation method for the expression of the CTL019 transgene. Initial production and release testing results and experience were gained by utilizing healthy donor starting material for manufacturing the cell product in our large scale GMP production facility. Patient-derived autologous CTL019 for treatment of pediatric patients with r/r ALL enrolled in a US-based, multicenter, phase II clinical trial have now been processed in the industry setting. Shipping logistics of the cryopreserved products (apheresis and CTL019) have been established. The cell expansion growth curves and release criteria on the cell products obtained in this large scale manufacturing facility were similar to those obtained at the academic facility.Conclusions: Leveraging a proven step-wise industry transfer process to capture academic experience along with extensive collaborative training and strong analytics led to this successful CAR cell therapy process transfer from academia to industry. This resulted in CTL019 cell expansion growth curves from our process that were similar to those observed from academia, which we anticipate will provide for global scalability. [Display omitted] DisclosuresBoyd:Novartis Pharmaceuticals Corporation: Employment. Levine:Novartis: Patents & Royalties, Research Funding. Jinivizian:Novartis Pharmaceuticals Corporation: Employment. Jeschke:Novartis Pharmaceuticals Corporation: Employment. Suhoski Davis:Novartis: Patents & Royalties. Zheng:Novartis: Patents & Royalties. Stark:Novartis Pharma AG: Employment. Loidolt:Novartis Pharmaceuticals Corporation: Employment. Keir:Novartis Pharmaceuticals Corporation: Employment. Wood:Novartis Pharmaceuticals Corporation: Employment.

A data pipeline for PHM data-driven analytics in large-scale smart manufacturing facilities


 
 
 The term smart manufacturing refers to a future-state of manufacturing, where the real-time transmission and processing of information across the factory will be used to produce advanced manufacturing intelligence that can optimize every aspect of its operation. In recent years, initiatives and groups such as the Smart Manufacturing Leadership Coalition (SMLC), Industry 4.0, and the Industrial Internet Consortium (IIC), have led the way by bringing together industry, academia and government to establish policies, roadmaps and platforms to support smart manufacturing. Although there are many characteristics that can be associated with smart manufacturing across these initiatives, a common theme is the emphasis on transitioning operations from reactive and responsive, to predictive and preventative. The research presented in this paper focuses on the development of a data pipeline that supports the development of data-driven Prognostics and Health Management (PHM) applications. In the context of smart manufacturing, PHM enables facilities to transition from preventative and reactive maintenance strategies, to predictive, preventative and condition-based strategies. The benefits that can be derived by PHM are aligned with those of smart manufacturing, which include the opportunity to decrease costs, increase machine availability, reduce energy consumption, and improve production yield.
 However, the process of ingesting, cleaning and transforming real-time data streams for data-driven PHM is a difficult, complex and time-consuming task, with estimates from business intelligence projects ranging from 80% to 90% of total project effort. This effort may only be exacerbated further in manufacturing environments due to additional technology challenges, such as low levels of standardization, disparate protocols and interfaces, and ad hoc data management. While emerging technologies such as Cyber Physical Systems (CPS) and Internet of Things (IoT) can overcome many of these challenges and provide an open platform for transmitting data, existing large-scale manufacturing facilities that are subject to compliance, regulation, and stringent quality
 
 
 assurance policies may not be able to adopt these technologies in the short-term due to the associated cost, risk and effort. Therefore, PHM applications that need to access data streams in large-scale manufacturing facilities must do so using transparent data integration that does not discriminate between emerging and legacy technologies in the factory. To this end, this research presents a real- time, scalable, robust, and fault tolerant data pipeline for ingesting, cleaning, transforming, processing and contextualizing time-series data from a wide-range of sources in the factory.
 
 

Wordsworth in America and the Nature of Democracy

D URING the post-Revolutionary decades, as the northern United States began to shift from an agrarian ex-colony into an industrial capitalist nation, country life and rural pursuits came to play a very specific role in the evolving selfdefinition of the region's ruling class. As Federalist urban elites went about building large-scale manufacturing facilities and financial institutions, they felt increasingly pressed to overcome the anti-commercial prejudices of the stalwart Jeffersonians who remained dominant in the countryside. So these new businessmen set out to occupy their enemy's high ground-by purchasing and settling large agricultural estates. On these model farms, they not only won ribbons for innovative agricultural techniques, but, more important, they harvested a rich crop of positive associations with rural life. Such benefits included the Puritan affirmation of a productive calling, the physiocratic idea that agriculture formed the true foundation of national prosperity, and the agrarian notion of virtuous producers defending the nation against luxury and vice. These country-seat Federalists fashioned themselves benevolent leaders, whose rationality and

A control-to-target architecture for process control

In this paper, we present an architecture for a run-to-run supervisory process control system that allows the engineer to tailor the form of control for specific processes. The architecture supports different degrees of control, from model-based control to statistical process control to diagnosis. The architecture is compatible with different techniques for model optimization, data acquisition and analysis, and model adjustment and feedback. A primary feature of this architecture is that engineers can define processes In terms of their desired effects, and use process models that transform those effects into machine settings. We have used object technology as the basis for our design and implementation of the architecture. Object-oriented modeling provides the flexibility required to support the varying degrees of control required in a large-scale manufacturing facility. In this paper, we define the components of the architecture, and describe in detail a process control system that was built with this architecture and used in the Computer Integrated manufacturing (CIM) system built for the Microelectronics Manufacturing Science and Technology (MMST) demonstration facility. Although the architecture was developed for the purpose of controlling semiconductor manufacturing processes, the principles behind the architecture may be applied to the control of any process. >

Analysis of a Kanban Discipline for Cell Coordination in Production Lines, II: Stochastic Demands

We describe and analyze a discipline called kanban for the control and coordination of cells in large-scale manufacturing facilities. There are many cells in tandem and also a process of arriving consumers; each consumer queues as long as necessary before departing with a product finished by the last cell. The coordination scheme relies on the circulation of a fixed number of cards (or kanbans) in each cell. This paper differs from our earlier paper in that here the process of consumers modulates the production process. Our results are in three parts. First, the kanban is compared to the classical production discipline and its (sample path) dominance in terms of the consumers' waiting time is proven. Second, we give an analytic scheme for approximating the performance of the stochastic kanban system by examining a single cell in isolation and then combining these through fixed-point equations. Ergodicity is equivalent in our approximation to the existence and uniqueness of a solution to the fixed-point equations and a complete, finite procedure for its resolution is obtained. Third, we report on experiments involving simulations and our method of analysis.

Analysis of a Kanban Discipline for Cell Coordination in Production Lines. I

We describe and analyze a discipline called kanban for the coordination of cells in a large-scale manufacturing facility. There are many cells in a tandem configuration and a fixed number of cards (or kanbans in Japanese usage) in each cell. The cards circulate within the cell and their presence at designated positions signals to the neighboring cells the status of the cell's inventory; rules specify the timing of the movement of parts from cell to cell. We construct a stochastic model of the whole manufacturing facility and give our results in three parts. First, the kanban discipline is compared to the classical production discipline and it is shown to dominate the classical discipline in terms of throughput. Secondly, we give a scheme for analyzing approximately the performance of the kanban system by examining first a single cell in isolation and then combining the isolated cells through fixed-point equations. Thirdly, we report on extensive experiments and on their numerical results which are obtained from simulations and our method of analysis. The throughput-inventory relationship of the kanban scheme is observed to be superior to that of the classical discipline.

Analysis of a Kanban Discipline for Cell Coordination in Production Lines. I

We describe and analyze a discipline called kanban for the coordination of cells in a large-scale manufacturing facility. There are many cells in a tandem configuration and a fixed number of cards ...

Amorphous-silicon solar cells

The status of a-Si solar cell technology is reviewed. This review includes a discussion of the types of solar cell structure that are being used in commercial products. An overview of the development efforts under way involving new materials, such as alloys and microcrystalline films, and their impact on device performance is given. The status of stability in a-Si solar cells and projections for costs for large-scale manufacturing facilities are reviewed. The development of markets for a-Si photovoltaics is also discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

Amorphous silicon solar cells

The status of a-Si solar cell technology is reviewed. This review includes a discussion of the types of solar cell structure that are being used in commercial products. An overview of the development efforts under way involving new materials, such as alloys and microcrystalline films, and their impact on device performance is given. The status of stability in a-Si solar cells and projections for costs for large-scale manufacturing facilities are reviewed. The development of markets for a-Si photovoltaics is also discussed. >