Manufacturing Squares: An Integrative Statistical Process Control Exercise

ERIC Educational Resources Information Center

Coy, Steven P.

2016-01-01

In the exercise, students in a junior-level operations management class are asked to manufacture a simple product. Given product specifications, they must design a production process, create roles and design jobs for each team member, and develop a statistical process control plan that efficiently and effectively controls quality during…

49 CFR 178.68 - Specification 4E welded aluminum cylinders.

Code of Federal Regulations, 2012 CFR

2012-10-01

... to cylinder by welding by inert gas shielded arc process or by threads. If threads are used, they... process and cylinders with longitudinal seams are not authorized. (b) Authorized material. The cylinder...'s lot number. (d) Manufacture. Cylinders must be manufactured using equipment and processes adequate...

49 CFR 178.68 - Specification 4E welded aluminum cylinders.

Code of Federal Regulations, 2014 CFR

2014-10-01

... to cylinder by welding by inert gas shielded arc process or by threads. If threads are used, they... process and cylinders with longitudinal seams are not authorized. (b) Authorized material. The cylinder...'s lot number. (d) Manufacture. Cylinders must be manufactured using equipment and processes adequate...

49 CFR 178.68 - Specification 4E welded aluminum cylinders.

Code of Federal Regulations, 2013 CFR

2013-10-01

... to cylinder by welding by inert gas shielded arc process or by threads. If threads are used, they... process and cylinders with longitudinal seams are not authorized. (b) Authorized material. The cylinder...'s lot number. (d) Manufacture. Cylinders must be manufactured using equipment and processes adequate...

49 CFR 178.59 - Specification 8 steel cylinders with porous fillings for acetylene.

Code of Federal Regulations, 2013 CFR

2013-10-01

... welded; (2) Attachment of heads by welding or by brazing by dipping process; or (3) A welded... oxygen process steel of uniform quality must be used. Content percent may not exceed the following... the heat number. (d) Manufacture. Cylinders must be manufactured using equipment and processes...

49 CFR 178.59 - Specification 8 steel cylinders with porous fillings for acetylene.

Code of Federal Regulations, 2012 CFR

2012-10-01

... welded; (2) Attachment of heads by welding or by brazing by dipping process; or (3) A welded... oxygen process steel of uniform quality must be used. Content percent may not exceed the following... the heat number. (d) Manufacture. Cylinders must be manufactured using equipment and processes...

49 CFR 178.59 - Specification 8 steel cylinders with porous fillings for acetylene.

Code of Federal Regulations, 2014 CFR

2014-10-01

... welded; (2) Attachment of heads by welding or by brazing by dipping process; or (3) A welded... oxygen process steel of uniform quality must be used. Content percent may not exceed the following... the heat number. (d) Manufacture. Cylinders must be manufactured using equipment and processes...

76 FR 74749 - Critical Parts for Airplane Propellers

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-01

... manufacturer, and establish engineering, manufacture, and maintenance processes for those parts. The intended... a specific definition for a propeller critical part, or-- [rtarr9] Require type certificate holders..., however, has regulations that identify a specific definition for propeller critical part, and regulations...

Manufacturing process for the WEAVE prime focus corrector optics for the 4.2m William Hershel Telescope

NASA Astrophysics Data System (ADS)

Lhomé, Emilie; Agócs, Tibor; Abrams, Don Carlos; Dee, Kevin M.; Middleton, Kevin F.; Tosh, Ian A.; Jaskó, Attila; Connor, Peter; Cochrane, Dave; Gers, Luke; Jonas, Graeme; Rakich, Andrew; Benn, Chris R.; Balcells, Marc; Trager, Scott C.; Dalton, Gavin B.; Carrasco, Esperanza; Vallenari, Antonella; Bonifacio, Piercarlo; Aguerri, J. Alfonso L.

2016-07-01

In this paper, we detail the manufacturing process for the lenses that will constitute the new two-degree field-of-view Prime Focus Corrector (PFC) for the 4.2m William Herschel Telescope (WHT) optimised for the upcoming WEAVE Multi-Object Spectroscopy (MOS) facility. The corrector, including an Atmospheric Dispersion Corrector (ADC), is made of six large lenses, the largest being 1.1-meter diameter. We describe how the prescriptions of the optical design were translated into manufacturing specifications for the blanks and lenses. We explain how the as-built glass blank parameters were fed back into the optical design and how the specifications for the lenses were subsequently modified. We review the critical issues for the challenging manufacturing process and discuss the trade-offs that were necessary to deliver the lenses while maintaining the optimal optical performance. A short description of the lens optical testing is also presented. Finally, the subsequent manufacturing steps, including assembly, integration, and alignment are outlined.

Automated manufacturing process for DEAP stack-actuators

NASA Astrophysics Data System (ADS)

Tepel, Dominik; Hoffstadt, Thorben; Maas, Jürgen

2014-03-01

Dielectric elastomers (DE) are thin polymer films belonging to the class of electroactive polymers (EAP), which are coated with compliant and conductive electrodes on each side. Due to the influence of an electrical field, dielectric elastomers perform a large amount of deformation. In this contribution a manufacturing process of automated fabricated stack-actuators based on dielectric electroactive polymers (DEAP) are presented. First of all the specific design of the considered stack-actuator is explained and afterwards the development, construction and realization of an automated manufacturing process is presented in detail. By applying this automated process, stack-actuators with reproducible and homogeneous properties can be manufactured. Finally, first DEAP actuator modules fabricated by the mentioned process are validated experimentally.

Overview of the Photovoltaic Manufacturing Technology (PVMaT) project

NASA Astrophysics Data System (ADS)

Witt, C. E.; Mitchell, R. L.; Mooney, G. D.

1993-08-01

The Photovoltaic Manufacturing Technology (PVMaT) project is a historic government/industry photovoltaic (PV) manufacturing R&D partnership composed of joint efforts between the federal government (through the US Department of Energy) and members of the US PV industry. The project's ultimate goal is to ensure that the US industry retains and extends its world leadership role in the manufacture and commercial development of PV components and systems. PVMaT is designed to do this by helping the US PV industry improve manufacturing processes, accelerate manufacturing cost reductions for PV modules, improve commercial product performance, and lay the groundwork for a substantial scale-up of US-based PV manufacturing capacities. Phase 1 of the project, the problem identification phase, was completed in early 1991. Phase 2, the problem solution phase, which addresses process-specific problems of specific manufacturers, is now underway with an expected duration of 5 years. Phase 3 addresses R&D problems that are relatively common to a number of PV companies or the PV industry as a whole. These 'generic' problem areas are being addressed through a teamed research approach.

Material Stream Strategy for Lithium and Inorganics (U)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Safarik, Douglas Joseph; Dunn, Paul Stanton; Korzekwa, Deniece Rochelle

Design Agency Responsibilities: Manufacturing Support to meet Stockpile Stewardship goals for maintaining the nuclear stockpile through experimental and predictive modeling capability. Development and maintenance of Manufacturing Science expertise to assess material specifications and performance boundaries, and their relationship to processing parameters. Production Engineering Evaluations with competence in design requirements, material specifications, and manufacturing controls. Maintenance and enhancement of Aging Science expertise to support Stockpile Stewardship predictive science capability.

49 CFR 178.70 - Approval of UN pressure receptacles.

Code of Federal Regulations, 2010 CFR

2010-10-01

... facility as specified in § 178.69. (7) Design specifications and manufacturing drawings, showing components... compliance with the applicable pressure receptacle design standard. (8) Manufacturing procedures and any applicable standards that describe in detail the manufacturing processes and control. (9) Design type...

21 CFR 111.365 - What precautions must you take to prevent contamination?

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING PRACTICE IN... necessary, the phase of manufacturing; and (k) Identifying all processing lines and major equipment used... specific batch or lot number and, when necessary, the phase of manufacturing. ...

Specificity of Good Manufacturing Practice (GMP) for Biomedical Cell Products.

PubMed

Tulina, M A; Pyatigorskaya, N V

2018-03-01

The article describes special aspects of Good Manufacturing Practice (GMP) for biomedical cell products (BMCP) that imply high standards of aseptics throughout the entire productio process, strict requirements to donors and to the procedure of biomaterial isolation, guaranty of tracing BMCP products, defining processing procedures which allow to identify BMCP as minimally manipulated; continuous quality control and automation of the control process at all stages of manufacturing, which will ensure product release simultaneously with completion of technological operations.

DARPA DICE Manufacturing Optimization

DTIC Science & Technology

1993-01-01

Entity ................................................... 13 3.3.4 Labor Entity ....................................................... 14 3.3.5 Equipment...51 4.2.13.4 Labor Specification .................................... 52 4.2.13.5 Facility Specification .................................. 543...resources. A I resource is any facility, labor , equipment, or consumable material used in the manufacturing U UNCLASSIFIED CDRL No.0002AB-5 process. A

Space Manufacturing: The Next Great Challenge

NASA Technical Reports Server (NTRS)

Whitaker, Ann F.; Curreri, Peter; Sharpe, Jonathan B.; Colberg, Wendell R.; Vickers, John H.

1998-01-01

Space manufacturing encompasses the research, development and manufacture necessary for the production of any product to be used in near zero gravity, and the production of spacecraft required for transporting research or production devices to space. Manufacturing for space, and manufacturing in space will require significant breakthroughs in materials and manufacturing technology, as well as in equipment designs. This report reviews some of the current initiatives in achieving space manufacturing. The first initiative deals with materials processing in space, e.g., processing non-terrestrial and terrestrial materials, especially metals. Some of the ramifications of the United States Microgravity Payloads fourth (USMP-4) mission are discussed. Some problems in non-terrestrial materials processing are mentioned. The second initiative is structures processing in space. In order to accomplish this, the International Space Welding Experiment was designed to demonstrate welding technology in near-zero gravity. The third initiative is advancements in earth-based manufacturing technologies necessary to achieve low cost access to space. The advancements discussed include development of lightweight material having high specific strength, and automated fabrication and manufacturing methods for these materials.

A Knowledge Database on Thermal Control in Manufacturing Processes

NASA Astrophysics Data System (ADS)

Hirasawa, Shigeki; Satoh, Isao

A prototype version of a knowledge database on thermal control in manufacturing processes, specifically, molding, semiconductor manufacturing, and micro-scale manufacturing has been developed. The knowledge database has search functions for technical data, evaluated benchmark data, academic papers, and patents. The database also displays trends and future roadmaps for research topics. It has quick-calculation functions for basic design. This paper summarizes present research topics and future research on thermal control in manufacturing engineering to collate the information to the knowledge database. In the molding process, the initial mold and melt temperatures are very important parameters. In addition, thermal control is related to many semiconductor processes, and the main parameter is temperature variation in wafers. Accurate in-situ temperature measurment of wafers is important. And many technologies are being developed to manufacture micro-structures. Accordingly, the knowledge database will help further advance these technologies.

Surface-specific additive manufacturing test artefacts

NASA Astrophysics Data System (ADS)

Townsend, Andrew; Racasan, Radu; Blunt, Liam

2018-06-01

Many test artefact designs have been proposed for use with additive manufacturing (AM) systems. These test artefacts have primarily been designed for the evaluation of AM form and dimensional performance. A series of surface-specific measurement test artefacts designed for use in the verification of AM manufacturing processes are proposed here. Surface-specific test artefacts can be made more compact because they do not require the large dimensions needed for accurate dimensional and form measurements. The series of three test artefacts are designed to provide comprehensive information pertaining to the manufactured surface. Measurement possibilities include deviation analysis, surface texture parameter data generation, sub-surface analysis, layer step analysis and build resolution comparison. The test artefacts are designed to provide easy access for measurement using conventional surface measurement techniques, for example, focus variation microscopy, stylus profilometry, confocal microscopy and scanning electron microscopy. Additionally, the test artefacts may be simply visually inspected as a comparative tool, giving a fast indication of process variation between builds. The three test artefacts are small enough to be included in every build and include built-in manufacturing traceability information, making them a convenient physical record of the build.

Design for Additive Bio-Manufacturing: From Patient-Specific Medical Devices to Rationally Designed Meta-Biomaterials.

PubMed

Zadpoor, Amir A

2017-07-25

Recent advances in additive manufacturing (AM) techniques in terms of accuracy, reliability, the range of processable materials, and commercial availability have made them promising candidates for production of functional parts including those used in the biomedical industry. The complexity-for-free feature offered by AM means that very complex designs become feasible to manufacture, while batch-size-indifference enables fabrication of fully patient-specific medical devices. Design for AM (DfAM) approaches aim to fully utilize those features for development of medical devices with substantially enhanced performance and biomaterials with unprecedented combinations of favorable properties that originate from complex geometrical designs at the micro-scale. This paper reviews the most important approaches in DfAM particularly those applicable to additive bio-manufacturing including image-based design pipelines, parametric and non-parametric designs, metamaterials, rational and computationally enabled design, topology optimization, and bio-inspired design. Areas with limited research have been identified and suggestions have been made for future research. The paper concludes with a brief discussion on the practical aspects of DfAM and the potential of combining AM with subtractive and formative manufacturing processes in so-called hybrid manufacturing processes.

Design for Additive Bio-Manufacturing: From Patient-Specific Medical Devices to Rationally Designed Meta-Biomaterials

PubMed Central

Zadpoor, Amir A.

2017-01-01

Recent advances in additive manufacturing (AM) techniques in terms of accuracy, reliability, the range of processable materials, and commercial availability have made them promising candidates for production of functional parts including those used in the biomedical industry. The complexity-for-free feature offered by AM means that very complex designs become feasible to manufacture, while batch-size-indifference enables fabrication of fully patient-specific medical devices. Design for AM (DfAM) approaches aim to fully utilize those features for development of medical devices with substantially enhanced performance and biomaterials with unprecedented combinations of favorable properties that originate from complex geometrical designs at the micro-scale. This paper reviews the most important approaches in DfAM particularly those applicable to additive bio-manufacturing including image-based design pipelines, parametric and non-parametric designs, metamaterials, rational and computationally enabled design, topology optimization, and bio-inspired design. Areas with limited research have been identified and suggestions have been made for future research. The paper concludes with a brief discussion on the practical aspects of DfAM and the potential of combining AM with subtractive and formative manufacturing processes in so-called hybrid manufacturing processes. PMID:28757572

Performance measurement integrated information framework in e-Manufacturing

NASA Astrophysics Data System (ADS)

Teran, Hilaida; Hernandez, Juan Carlos; Vizán, Antonio; Ríos, José

2014-11-01

The implementation of Internet technologies has led to e-Manufacturing technologies becoming more widely used and to the development of tools for compiling, transforming and synchronising manufacturing data through the Web. In this context, a potential area for development is the extension of virtual manufacturing to performance measurement (PM) processes, a critical area for decision making and implementing improvement actions in manufacturing. This paper proposes a PM information framework to integrate decision support systems in e-Manufacturing. Specifically, the proposed framework offers a homogeneous PM information exchange model that can be applied through decision support in e-Manufacturing environment. Its application improves the necessary interoperability in decision-making data processing tasks. It comprises three sub-systems: a data model, a PM information platform and PM-Web services architecture. A practical example of data exchange for measurement processes in the area of equipment maintenance is shown to demonstrate the utility of the model.

7 CFR 58.705 - Meaning of words.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., GENERAL SPECIFICATIONS FOR APPROVED PLANTS AND STANDARDS FOR GRADES OF DAIRY PRODUCTS 1 General Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Supplemental Specifications for Plants Manufacturing, Processing and Packaging Pasteurized Process Cheese and Related Products...

7 CFR 58.705 - Meaning of words.

Code of Federal Regulations, 2012 CFR

2012-01-01

..., GENERAL SPECIFICATIONS FOR APPROVED PLANTS AND STANDARDS FOR GRADES OF DAIRY PRODUCTS 1 General Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Supplemental Specifications for Plants Manufacturing, Processing and Packaging Pasteurized Process Cheese and Related Products...

7 CFR 58.705 - Meaning of words.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., GENERAL SPECIFICATIONS FOR APPROVED PLANTS AND STANDARDS FOR GRADES OF DAIRY PRODUCTS 1 General Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Supplemental Specifications for Plants Manufacturing, Processing and Packaging Pasteurized Process Cheese and Related Products...

7 CFR 58.705 - Meaning of words.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., GENERAL SPECIFICATIONS FOR APPROVED PLANTS AND STANDARDS FOR GRADES OF DAIRY PRODUCTS 1 General Specifications for Dairy Plants Approved for USDA Inspection and Grading Service 1 Supplemental Specifications for Plants Manufacturing, Processing and Packaging Pasteurized Process Cheese and Related Products...

Considerations for setting the specifications of vaccines.

PubMed

Minor, Philip

2012-05-01

The specifications of vaccines are determined by the particular product and its method of manufacture, which raise issues unique to the vaccine in question. However, the general principles are shared, including the need to have sufficient active material to immunize a very high proportion of recipients, an acceptable level of safety, which may require specific testing or may come from the production process, and an acceptable low level of contamination with unwanted materials, which may include infectious agents or materials used in production. These principles apply to the earliest smallpox vaccines and the most recent recombinant vaccines, such as those against HPV. Manufacturing development includes more precise definitions of the product through improved tests and tighter control of the process parameters. Good manufacturing practice plays a major role, which is likely to increase in importance in assuring product quality almost independent of end-product specifications.

Manufacturing process applications team (MATeam)

NASA Technical Reports Server (NTRS)

Bangs, E. R.

1980-01-01

Progress in the transfer of aerospace technology to solve key problems in the manufacturing sector of the economy is reported. Potential RTOP programs are summarized along with dissemination activities. The impact of transferred NASA manufacturing technology is discussed. Specific areas covered include aircraft production, robot technology, machining of alloys, and electrical switching systems.

Current manufacturing processes of drug-eluting sutures.

PubMed

Champeau, Mathilde; Thomassin, Jean-Michel; Tassaing, Thierry; Jérôme, Christine

2017-11-01

Drug-eluting sutures represent the next generation of surgical sutures since they fulfill their mechanical functions but also deliver the drug in their vicinity after implantation. These implants are produced by a variety of manufacturing processes. Drug-eluting sutures represent the next generation of surgical sutures since they fulfill their mechanical functions but also deliver the drug in their vicinity after implantation. These implants are produced by a variety of manufacturing processes. Two general approaches can be followed: (i) the ones that add the API into the material during the manufacturing process of the suture and (ii) the ones that load the API to an already manufactured suture. Areas covered: This review provides an overview of the current manufacturing processes for drug-eluting suture production and discusses their benefits and drawbacks depending on the type of drugs. The mechanical properties and the drug delivery profile of drug-eluting sutures are highlighted since these implants must fulfill both criteria. Expert opinion: For limited drug contents, melt extrusion and electrospinning are the emerging processes since the drug is added during the suture manufacture process. Advantageously, the drug release profile can be tuned by controlling the processing parameters specific to each process and the composition of the drug-containing polymer. If high drug content is targeted, the coating or grafting of a drug layer on a pre-manufactured suture allows for preservation of the tensile strength requirements of the suture.

49 CFR 178.53 - Specification 4D welded steel cylinders for aircraft use.

Code of Federal Regulations, 2014 CFR

2014-10-01

... in by spinning process are not authorized. (b) Steel. Open-hearth or electric steel of uniform and.... (d) Manufacture. Cylinders must be manufactured using equipment and processes adequate to ensure that... fitting, boss, or pad, securely attached to the container by brazing or by welding or by threads. If...

49 CFR 178.53 - Specification 4D welded steel cylinders for aircraft use.

Code of Federal Regulations, 2013 CFR

2013-10-01

... in by spinning process are not authorized. (b) Steel. Open-hearth or electric steel of uniform and.... (d) Manufacture. Cylinders must be manufactured using equipment and processes adequate to ensure that... fitting, boss, or pad, securely attached to the container by brazing or by welding or by threads. If...

49 CFR 178.53 - Specification 4D welded steel cylinders for aircraft use.

Code of Federal Regulations, 2012 CFR

2012-10-01

... in by spinning process are not authorized. (b) Steel. Open-hearth or electric steel of uniform and.... (d) Manufacture. Cylinders must be manufactured using equipment and processes adequate to ensure that... fitting, boss, or pad, securely attached to the container by brazing or by welding or by threads. If...

Essential Aspects in Assessing the Safety Impact of Interactions between a Drug Product and Its Associated Manufacturing System.

PubMed

Jenke, Dennis

2012-01-01

An emerging trend in the biotechnology industry is the utilization of plastic components in manufacturing systems for the production of an active pharmaceutical ingredient (API) or a finished drug product (FDP). If the API, the FDP, or any solution used to generate them (for example, process streams such as media, buffers, and the like) come in contact with a plastic at any time during the manufacturing process, there is the potential that substances leached from the plastic may accumulate in the API or FDP, affecting safety and/or efficacy. In this article the author develops a terminology that addresses process streams associated with the manufacturing process. Additionally, the article outlines the safety assessment process for manufacturing systems, specifically addressing the topics of risk management and the role of compendial testing. Finally, the proper use of vendor-supplied extractables information is considered. Manufacturing suites used to produce biopharmaceuticals can include components that are made out of plastics. Thus it is possible that substances could leach out of the plastics and into manufacturing solutions, and it is further possible that such leachables could accumulate in the pharmaceutical product. In this article, the author develops a terminology that addresses process streams associated with the manufacturing process. Additionally, the author proposes a process by which the impact on product safety of such leached substances can be assessed.

Evaluation of the quality of generic polymethylmethacrylate intraocular lenses marketed in India.

PubMed

Combe, R; Watkins, R; Brian, G

2001-04-01

To determine the quality of single-piece, allpolymethylmethacrylate (PMMA) Intraocular lenses (IOLs) from eght generic manufacturers marketing their product in India. This assessment of quality was made with respect to compliance with internationa standards for the manufacture of IOLs, specifically those parameters most likely to affect patient postoperat ve visual acuity and the long-term biocompatibility of the implanted lens. Ten IOLs from each of eight manufacturers were purchased randomly from commercial retail outlets in India. Each IOL, in a masked fashion, had its physical dimensions, optical performance and cosmetic appearance assessed, using the methods prescribed in ISO 11979-2 and 11979-3. Validation of manufacturing process controls were determined by statistical process contro techniques. Four IOLs from each manufacturer were also tested for the presence of unpolymerized PMMA using gas chromatography. Only lenses from two IOL manufacturers complied with the optical and mechanical standards. All other manufacturers' lenses failed one or more of these tests. Intraocular lenses from only two producers met with surface quality and bulk homogeneity standards. All others exhibited defects such as surface contamination and scratches, poor polishing, and chipped or rough positioning holes. Lenses from two producers exhibited high levels of methylmethacrylate monomer (MMA). Non-clinical grade PMMA starting material may have been used in the manufacture of IOLs by some producers. Critical manufacturing defects occurred in the IOLs from five of the eight producers tested. Only one manufacturer's IOLs met all specifications, and on statistical analysis demonstrated good manufacturing process contro with respect to the properties tested. With the widespread acceptance of IOL implantation in developing countries, such as India, it is essential that in the rush to make this the norm, the quality of implants used not be overlooked.

Quantification of uncertainty in machining operations for on-machine acceptance.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Claudet, Andre A.; Tran, Hy D.; Su, Jiann-Chemg

2008-09-01

Manufactured parts are designed with acceptance tolerances, i.e. deviations from ideal design conditions, due to unavoidable errors in the manufacturing process. It is necessary to measure and evaluate the manufactured part, compared to the nominal design, to determine whether the part meets design specifications. The scope of this research project is dimensional acceptance of machined parts; specifically, parts machined using numerically controlled (NC, or also CNC for Computer Numerically Controlled) machines. In the design/build/accept cycle, the designer will specify both a nominal value, and an acceptable tolerance. As part of the typical design/build/accept business practice, it is required to verifymore » that the part did meet acceptable values prior to acceptance. Manufacturing cost must include not only raw materials and added labor, but also the cost of ensuring conformance to specifications. Ensuring conformance is a substantial portion of the cost of manufacturing. In this project, the costs of measurements were approximately 50% of the cost of the machined part. In production, cost of measurement would be smaller, but still a substantial proportion of manufacturing cost. The results of this research project will point to a science-based approach to reducing the cost of ensuring conformance to specifications. The approach that we take is to determine, a priori, how well a CNC machine can manufacture a particular geometry from stock. Based on the knowledge of the manufacturing process, we are then able to decide features which need further measurements from features which can be accepted 'as is' from the CNC. By calibration of the machine tool, and establishing a machining accuracy ratio, we can validate the ability of CNC to fabricate to a particular level of tolerance. This will eliminate the costs of checking for conformance for relatively large tolerances.« less

Low-cost manufacturing of the point focus concentrating module and its key component, the Fresnel lens. Final subcontract report, 31 January 1991--6 May 1991

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saifee, T.; Konnerth, A. III

1991-11-01

Solar Kinetics, Inc. (SKI) has been developing point-focus concentrating PV modules since 1986. SKI is currently in position to manufacture between 200 to 600 kilowatts annually of the current design by a combination of manual and semi-automated methods. This report reviews the current status of module manufacture and specifies the required approach to achieve a high-volume manufacturing capability and low cost. The approach taken will include process development concurrent with module design for automated manufacturing. The current effort reviews the major manufacturing costs and identifies components and processes whose improvements would produce the greatest effect on manufacturability and cost reduction.more » The Fresnel lens is one such key component. Investigating specific alternative manufacturing methods and sources has substantially reduced the lens costs and has exceeded the DOE cost-reduction goals. 15 refs.« less

CIM's bridge from CADD to CAM: Data management requirements for manufacturing engineering

NASA Technical Reports Server (NTRS)

Ford, S. J.

1984-01-01

Manufacturing engineering represents the crossroads of technical data management in a Computer Integrated Manufacturing (CIM) environment. Process planning, numerical control programming and tool design are the key functions which translate information from as engineered to as assembled. In order to transition data from engineering to manufacturing, it is necessary to introduce a series of product interpretations which contain an interim introduction of technical parameters. The current automation of the product definition and the production process places manufacturing engineering in the center of CAD/CAM with the responsibility of communicating design data to the factory floor via a manufacturing model of the data. A close look at data management requirements for manufacturing engineering is necessary in order to establish the overall specifications for CADD output, CAM input, and CIM integration. The functions and issues associated with the orderly evolution of computer aided engineering and manufacturing are examined.

National Institutes of Health-Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial: Manufacture of a Complex Cellular Product at Eight Processing Facilities.

PubMed

Ricordi, Camillo; Goldstein, Julia S; Balamurugan, A N; Szot, Gregory L; Kin, Tatsuya; Liu, Chengyang; Czarniecki, Christine W; Barbaro, Barbara; Bridges, Nancy D; Cano, Jose; Clarke, William R; Eggerman, Thomas L; Hunsicker, Lawrence G; Kaufman, Dixon B; Khan, Aisha; Lafontant, David-Erick; Linetsky, Elina; Luo, Xunrong; Markmann, James F; Naji, Ali; Korsgren, Olle; Oberholzer, Jose; Turgeon, Nicole A; Brandhorst, Daniel; Chen, Xiaojuan; Friberg, Andrew S; Lei, Ji; Wang, Ling-Jia; Wilhelm, Joshua J; Willits, Jamie; Zhang, Xiaomin; Hering, Bernhard J; Posselt, Andrew M; Stock, Peter G; Shapiro, A M James; Chen, Xiaojuan

2016-11-01

Eight manufacturing facilities participating in the National Institutes of Health-sponsored Clinical Islet Transplantation (CIT) Consortium jointly developed and implemented a harmonized process for the manufacture of allogeneic purified human pancreatic islet (PHPI) product evaluated in a phase 3 trial in subjects with type 1 diabetes. Manufacturing was controlled by a common master production batch record, standard operating procedures that included acceptance criteria for deceased donor organ pancreata and critical raw materials, PHPI product specifications, certificate of analysis, and test methods. The process was compliant with Current Good Manufacturing Practices and Current Good Tissue Practices. This report describes the manufacturing process for 75 PHPI clinical lots and summarizes the results, including lot release. The results demonstrate the feasibility of implementing a harmonized process at multiple facilities for the manufacture of a complex cellular product. The quality systems and regulatory and operational strategies developed by the CIT Consortium yielded product lots that met the prespecified characteristics of safety, purity, potency, and identity and were successfully transplanted into 48 subjects. No adverse events attributable to the product and no cases of primary nonfunction were observed. © 2016 by the American Diabetes Association.

National Institutes of Health–Sponsored Clinical Islet Transplantation Consortium Phase 3 Trial: Manufacture of a Complex Cellular Product at Eight Processing Facilities

PubMed Central

Balamurugan, A.N.; Szot, Gregory L.; Kin, Tatsuya; Liu, Chengyang; Czarniecki, Christine W.; Barbaro, Barbara; Bridges, Nancy D.; Cano, Jose; Clarke, William R.; Eggerman, Thomas L.; Hunsicker, Lawrence G.; Kaufman, Dixon B.; Khan, Aisha; Lafontant, David-Erick; Linetsky, Elina; Luo, Xunrong; Markmann, James F.; Naji, Ali; Korsgren, Olle; Oberholzer, Jose; Turgeon, Nicole A.; Brandhorst, Daniel; Chen, Xiaojuan; Friberg, Andrew S.; Lei, Ji; Wang, Ling-jia; Wilhelm, Joshua J.; Willits, Jamie; Zhang, Xiaomin; Hering, Bernhard J.; Posselt, Andrew M.; Stock, Peter G.; Shapiro, A.M. James

2016-01-01

Eight manufacturing facilities participating in the National Institutes of Health–sponsored Clinical Islet Transplantation (CIT) Consortium jointly developed and implemented a harmonized process for the manufacture of allogeneic purified human pancreatic islet (PHPI) product evaluated in a phase 3 trial in subjects with type 1 diabetes. Manufacturing was controlled by a common master production batch record, standard operating procedures that included acceptance criteria for deceased donor organ pancreata and critical raw materials, PHPI product specifications, certificate of analysis, and test methods. The process was compliant with Current Good Manufacturing Practices and Current Good Tissue Practices. This report describes the manufacturing process for 75 PHPI clinical lots and summarizes the results, including lot release. The results demonstrate the feasibility of implementing a harmonized process at multiple facilities for the manufacture of a complex cellular product. The quality systems and regulatory and operational strategies developed by the CIT Consortium yielded product lots that met the prespecified characteristics of safety, purity, potency, and identity and were successfully transplanted into 48 subjects. No adverse events attributable to the product and no cases of primary nonfunction were observed. PMID:27465220

Virtual Manufacturing of Composite Structures for Ground Platforms, A DARPA Instant Foundry Adaptive Through Bits (iFAB) Program

DTIC Science & Technology

2012-08-01

This document contains color. 14. ABSTRACT This effort focused specifically on the Liquid Composite Molding (LCM) class of processes as they...SUBJECT TERMS Liquid Composite Molding (LCM), fabrication, manufacturability assessment 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF... Molding (LCM) .......................................................................... 2 1.1.1 LCM Process Variations

Optimization Manufacture of Virus- and Tumor-Specific T Cells

PubMed Central

Lapteva, Natalia; Vera, Juan F.

2011-01-01

Although ex vivo expanded T cells are currently widely used in pre-clinical and clinical trials, the complexity of manufacture remains a major impediment for broader application. In this review we discuss current protocols for the ex vivo expansion of virus- and tumor-specific T cells and describe our experience in manufacture optimization using a gas-permeable static culture flask (G-Rex). This innovative device has revolutionized the manufacture process by allowing us to increase cell yields while decreasing the frequency of cell manipulation and in vitro culture time. It is now being used in good manufacturing practice (GMP) facilities for clinical cell production in our institution as well as many others in the US and worldwide. PMID:21915183

Additive Manufacturing of Fuel Injectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sadek Tadros, Dr. Alber Alphonse; Ritter, Dr. George W.; Drews, Charles Donald

Additive manufacturing (AM), also known as 3D-printing, has been shifting from a novelty prototyping paradigm to a legitimate manufacturing tool capable of creating components for highly complex engineered products. An emerging AM technology for producing metal parts is the laser powder bed fusion (L-PBF) process; however, industry manufacturing specifications and component design practices for L-PBF have not yet been established. Solar Turbines Incorporated (Solar), an industrial gas turbine manufacturer, has been evaluating AM technology for development and production applications with the desire to enable accelerated product development cycle times, overall turbine efficiency improvements, and supply chain flexibility relative to conventionalmore » manufacturing processes (casting, brazing, welding). Accordingly, Solar teamed with EWI on a joint two-and-a-half-year project with the goal of developing a production L-PBF AM process capable of consistently producing high-nickel alloy material suitable for high temperature gas turbine engine fuel injector components. The project plan tasks were designed to understand the interaction of the process variables and their combined impact on the resultant AM material quality. The composition of the high-nickel alloy powders selected for this program met the conventional cast Hastelloy X compositional limits and were commercially available in different particle size distributions (PSD) from two suppliers. Solar produced all the test articles and both EWI and Solar shared responsibility for analyzing them. The effects of powder metal input stock, laser parameters, heat treatments, and post-finishing methods were evaluated. This process knowledge was then used to generate tensile, fatigue, and creep material properties data curves suitable for component design activities. The key process controls for ensuring consistent material properties were documented in AM powder and process specifications. The basic components of the project were: • Powder metal input stock: Powder characterization, dimensional accuracy, metallurgical characterization, and mechanical properties evaluation. • Process parameters: Laser parameter effects, post-printing heat-treatment development, mechanical properties evaluation, and post-finishing technique. • Material design curves: Room and elevated temperature tensiles, low cycle fatigue, and creep rupture properties curves generated. • AM specifications: Key metal powder characteristics, laser parameters, and heat-treatment controls identified.« less

Control of three different continuous pharmaceutical manufacturing processes: Use of soft sensors.

PubMed

Rehrl, Jakob; Karttunen, Anssi-Pekka; Nicolaï, Niels; Hörmann, Theresa; Horn, Martin; Korhonen, Ossi; Nopens, Ingmar; De Beer, Thomas; Khinast, Johannes G

2018-05-30

One major advantage of continuous pharmaceutical manufacturing over traditional batch manufacturing is the possibility of enhanced in-process control, reducing out-of-specification and waste material by appropriate discharge strategies. The decision on material discharge can be based on the measurement of active pharmaceutical ingredient (API) concentration at specific locations in the production line via process analytic technology (PAT), e.g. near-infrared (NIR) spectrometers. The implementation of the PAT instruments is associated with monetary investment and the long term operation requires techniques avoiding sensor drifts. Therefore, our paper proposes a soft sensor approach for predicting the API concentration from the feeder data. In addition, this information can be used to detect sensor drift, or serve as a replacement/supplement of specific PAT equipment. The paper presents the experimental determination of the residence time distribution of selected unit operations in three different continuous processing lines (hot melt extrusion, direct compaction, wet granulation). The mathematical models describing the soft sensor are developed and parameterized. Finally, the suggested soft sensor approach is validated on the three mentioned, different continuous processing lines, demonstrating its versatility. Copyright © 2018 Elsevier B.V. All rights reserved.

Additive Manufacturing Processes: Selective Laser Melting, Electron Beam Melting and Binder Jetting—Selection Guidelines

PubMed Central

Konda Gokuldoss, Prashanth; Kolla, Sri; Eckert, Jürgen

2017-01-01

Additive manufacturing (AM), also known as 3D printing or rapid prototyping, is gaining increasing attention due to its ability to produce parts with added functionality and increased complexities in geometrical design, on top of the fact that it is theoretically possible to produce any shape without limitations. However, most of the research on additive manufacturing techniques are focused on the development of materials/process parameters/products design with different additive manufacturing processes such as selective laser melting, electron beam melting, or binder jetting. However, we do not have any guidelines that discuss the selection of the most suitable additive manufacturing process, depending on the material to be processed, the complexity of the parts to be produced, or the design considerations. Considering the very fact that no reports deal with this process selection, the present manuscript aims to discuss the different selection criteria that are to be considered, in order to select the best AM process (binder jetting/selective laser melting/electron beam melting) for fabricating a specific component with a defined set of material properties. PMID:28773031

Additive Manufacturing Processes: Selective Laser Melting, Electron Beam Melting and Binder Jetting-Selection Guidelines.

PubMed

Gokuldoss, Prashanth Konda; Kolla, Sri; Eckert, Jürgen

2017-06-19

Additive manufacturing (AM), also known as 3D printing or rapid prototyping, is gaining increasing attention due to its ability to produce parts with added functionality and increased complexities in geometrical design, on top of the fact that it is theoretically possible to produce any shape without limitations. However, most of the research on additive manufacturing techniques are focused on the development of materials/process parameters/products design with different additive manufacturing processes such as selective laser melting, electron beam melting, or binder jetting. However, we do not have any guidelines that discuss the selection of the most suitable additive manufacturing process, depending on the material to be processed, the complexity of the parts to be produced, or the design considerations. Considering the very fact that no reports deal with this process selection, the present manuscript aims to discuss the different selection criteria that are to be considered, in order to select the best AM process (binder jetting/selective laser melting/electron beam melting) for fabricating a specific component with a defined set of material properties.

A modular assembling platform for manufacturing of microsystems by optical tweezers

NASA Astrophysics Data System (ADS)

Ksouri, Sarah Isabelle; Aumann, Andreas; Ghadiri, Reza; Prüfer, Michael; Baer, Sebastian; Ostendorf, Andreas

2013-09-01

Due to the increased complexity in terms of materials and geometries for microsystems new assembling techniques are required. Assembling techniques from the semiconductor industry are often very specific and cannot fulfill all specifications in more complex microsystems. Therefore, holographic optical tweezers are applied to manipulate structures in micrometer range with highest flexibility and precision. As is well known non-spherical assemblies can be trapped and controlled by laser light and assembled with an additional light modulator application, where the incident laser beam is rearranged into flexible light patterns in order to generate multiple spots. The complementary building blocks are generated by a two-photon-polymerization process. The possibilities of manufacturing arbitrary microstructures and the potential of optical tweezers lead to the idea of combining manufacturing techniques with manipulation processes to "microrobotic" processes. This work presents the manipulation of generated complex microstructures with optical tools as well as a storage solution for 2PP assemblies. A sample holder has been developed for the manual feeding of 2PP building blocks. Furthermore, a modular assembling platform has been constructed for an `all-in-one' 2PP manufacturing process as a dedicated storage system. The long-term objective is the automation process of feeding and storage of several different 2PP micro-assemblies to realize an automated assembly process.

Achieving Continuous Manufacturing for Final Dosage Formation: Challenges and How to Meet Them May 20-21 2014 Continuous Manufacturing Symposium.

PubMed

Byrn, Stephen; Futran, Maricio; Thomas, Hayden; Jayjock, Eric; Maron, Nicola; Meyer, Robert F; Myerson, Allan S; Thien, Michael P; Trout, Bernhardt L

2015-03-01

We describe the key issues and possibilities for continuous final dosage formation, otherwise known as downstream processing or drug product manufacturing. A distinction is made between heterogeneous processing and homogeneous processing, the latter of which is expected to add more value to continuous manufacturing. We also give the key motivations for moving to continuous manufacturing, some of the exciting new technologies, and the barriers to implementation of continuous manufacturing. Continuous processing of heterogeneous blends is the natural first step in converting existing batch processes to continuous. In heterogeneous processing, there are discrete particles that can segregate, versus in homogeneous processing, components are blended and homogenized such that they do not segregate. Heterogeneous processing can incorporate technologies that are closer to existing technologies, where homogeneous processing necessitates the development and incorporation of new technologies. Homogeneous processing has the greatest potential for reaping the full rewards of continuous manufacturing, but it takes long-term vision and a more significant change in process development than heterogeneous processing. Heterogeneous processing has the detriment that, as the technologies are adopted rather than developed, there is a strong tendency to incorporate correction steps, what we call below "The Rube Goldberg Problem." Thus, although heterogeneous processing will likely play a major role in the near-term transformation of heterogeneous to continuous processing, it is expected that homogeneous processing is the next step that will follow. Specific action items for industry leaders are. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Fabricating specialised orthopaedic implants using additive manufacturing

NASA Astrophysics Data System (ADS)

Unwin, Paul

2014-03-01

It has been hypothesised that AM is ideal for patient specific orthopaedic implants such as those used in bone cancer treatment, that can rapidly build structures such as lattices for bone and tissues to in-grow, that would be impossible using current conventional subtractive manufacturing techniques. The aim of this study was to describe the adoption of AM (direct metal laser sintering and electron beam melting) into the design manufacturing and post-manufacturing processes and the early clinical use. Prior to the clinical use of AM implants, extensive metallurgical and mechanical testing of both laser and electron beam fabrications were undertaken. Concurrently, post-manufacturing processes evaluated included hipping, cleaning and coating treatments. The first clinical application of a titanium alloy mega-implant was undertaken in November 2010. A 3D model of the pelvic wing implant was designed from CT scans. Novel key features included extensive lattice structures at the bone interfaces and integral flanges to fix the implant to the bone. The pelvic device was implanted with the aid of navigation and to date the patient remains active. A further 18 patient specific mega-implants have now been implanted. The early use of this advanced manufacturing route for patient specific implants has been very encouraging enabling the engineer to produce more advanced and anatomical conforming implants. However, there are a new set of design, manufacturing and regulatory challenges that require addressing to permit this technique to be used more widely. This technology is changing the design and manufacturing paradigm for the fabrication of specialised orthopaedic implants.

Design and manufacturing of patient-specific orthodontic appliances by computer-aided engineering techniques.

PubMed

Barone, Sandro; Neri, Paolo; Paoli, Alessandro; Razionale, Armando Viviano

2018-01-01

Orthodontic treatments are usually performed using fixed brackets or removable oral appliances, which are traditionally made from alginate impressions and wax registrations. Among removable devices, eruption guidance appliances are used for early orthodontic treatments in order to intercept and prevent malocclusion problems. Commercially available eruption guidance appliances, however, are symmetric devices produced using a few standard sizes. For this reason, they are not able to meet all the specific patient's needs since the actual dental anatomies present various geometries and asymmetric conditions. In this article, a computer-aided design-based methodology for the design and manufacturing of a patient-specific eruption guidance appliances is presented. The proposed approach is based on the digitalization of several steps of the overall process: from the digital reconstruction of patients' anatomies to the manufacturing of customized appliances. A finite element model has been developed to evaluate the temporomandibular joint disks stress level caused by using symmetric eruption guidance appliances with different teeth misalignment conditions. The developed model can then be used to guide the design of a patient-specific appliance with the aim at reducing the patient discomfort. At this purpose, two different customization levels are proposed in order to face both arches and single tooth misalignment issues. A low-cost manufacturing process, based on an additive manufacturing technique, is finally presented and discussed.

Integration Framework of Process Planning based on Resource Independent Operation Summary to Support Collaborative Manufacturing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kulvatunyou, Boonserm; Wysk, Richard A.; Cho, Hyunbo

2004-06-01

In today's global manufacturing environment, manufacturing functions are distributed as never before. Design, engineering, fabrication, and assembly of new products are done routinely in many different enterprises scattered around the world. Successful business transactions require the sharing of design and engineering data on an unprecedented scale. This paper describes a framework that facilitates the collaboration of engineering tasks, particularly process planning and analysis, to support such globalized manufacturing activities. The information models of data and the software components that integrate those information models are described. The integration framework uses an Integrated Product and Process Data (IPPD) representation called a Resourcemore » Independent Operation Summary (RIOS) to facilitate the communication of business and manufacturing requirements. Hierarchical process modeling, process planning decomposition and an augmented AND/OR directed graph are used in this representation. The Resource Specific Process Planning (RSPP) module assigns required equipment and tools, selects process parameters, and determines manufacturing costs based on two-level hierarchical RIOS data. The shop floor knowledge (resource and process knowledge) and a hybrid approach (heuristic and linear programming) to linearize the AND/OR graph provide the basis for the planning. Finally, a prototype system is developed and demonstrated with an exemplary part. Java and XML (Extensible Markup Language) are used to ensure software and information portability.« less

Volatile organic compound (VOC) emissions during malting and beer manufacture

NASA Astrophysics Data System (ADS)

Gibson, Nigel B.; Costigan, Gavin T.; Swannell, Richard P. J.; Woodfield, Michael J.

Estimates have been made of the amounts of volatile organic compounds (VOCs) released during different stages of beer manufacture. The estimates are based on recent measurements and plant specification data supplied by manufacturers. Data were obtained for three main manufacturing processes (malting, wort processing and fermentation) for three commercial beer types. Some data on the speciation of emitted compounds have been obtained. Based on these measurements, an estimate of the total unabated VOC emission. from the U.K. brewing industry was calculated as 3.5 kta -1, over 95% of which was generated during barley malting. This value does not include any correction for air pollution control.

Comparison Through Image Analysis Between Al Foams Produced Using Two Different Methods

NASA Astrophysics Data System (ADS)

Boschetto, A.; Campana, F.; Pilone, D.

2014-02-01

Several methods are available for making metal foams. They allow to tailor their mechanical, thermal, acoustic, and electrical properties for specific applications by varying the relative density as well as the cell size and morphology. Foams have a very heterogeneous structure so that their properties may show a large scatter. In this paper, an aluminum foam produced by means of foaming of powder compacts and another one prepared via the infiltration process were analyzed and compared. Image analysis has been used as a useful tool to determine size, morphology, and distribution of cells in both foams and to correlate cell morphology with the considered manufacturing process. The results highlighted that cell size and morphology are strictly dependent upon the manufacturing method. This paper shows how some standard 2D morphological indicators may be usefully adopted to characterize foams whose structure derives from the specific manufacturing process.

Building a Competitive Edge with Additive Manufacturing

DTIC Science & Technology

2013-02-14

construct ceramic molds for complex metal parts using a 3D printing technique. They estimate the new 6 technique could eliminate all of the...processes. They include 3D printing and Additive Beam Techniques.15 Most Additive Manufacturing techniques are specific to certain classes of materials...9 Example Additive Manufacturing Techniques16 3D Printing Additive Beam Stereolithography (SLA) Direct Metal Laser Sintering (DMLS

Identifying Critical Manufacturing Technologies Required for Transforming the Army Industrial Base

DTIC Science & Technology

2014-04-01

mechanism, 1 = least common mechanism)? ................................................................... 29 Figure 5 – Which Technology “ Test Beds...facilities, produce new designs , and incorporate efficient manufacturing processes. The value and continued success of the Army Industrial Base depends on...in materiel supplies to troops. Specific programs, described in AR 700-09, that are designed to transition manufacturing technology into the Army

A quality risk management model approach for cell therapy manufacturing.

PubMed

Lopez, Fabio; Di Bartolo, Chiara; Piazza, Tommaso; Passannanti, Antonino; Gerlach, Jörg C; Gridelli, Bruno; Triolo, Fabio

2010-12-01

International regulatory authorities view risk management as an essential production need for the development of innovative, somatic cell-based therapies in regenerative medicine. The available risk management guidelines, however, provide little guidance on specific risk analysis approaches and procedures applicable in clinical cell therapy manufacturing. This raises a number of problems. Cell manufacturing is a poorly automated process, prone to operator-introduced variations, and affected by heterogeneity of the processed organs/tissues and lot-dependent variability of reagent (e.g., collagenase) efficiency. In this study, the principal challenges faced in a cell-based product manufacturing context (i.e., high dependence on human intervention and absence of reference standards for acceptable risk levels) are identified and addressed, and a risk management model approach applicable to manufacturing of cells for clinical use is described for the first time. The use of the heuristic and pseudo-quantitative failure mode and effect analysis/failure mode and critical effect analysis risk analysis technique associated with direct estimation of severity, occurrence, and detection is, in this specific context, as effective as, but more efficient than, the analytic hierarchy process. Moreover, a severity/occurrence matrix and Pareto analysis can be successfully adopted to identify priority failure modes on which to act to mitigate risks. The application of this approach to clinical cell therapy manufacturing in regenerative medicine is also discussed. © 2010 Society for Risk Analysis.

The effects of gray scale image processing on digital mammography interpretation performance.

PubMed

Cole, Elodia B; Pisano, Etta D; Zeng, Donglin; Muller, Keith; Aylward, Stephen R; Park, Sungwook; Kuzmiak, Cherie; Koomen, Marcia; Pavic, Dag; Walsh, Ruth; Baker, Jay; Gimenez, Edgardo I; Freimanis, Rita

2005-05-01

To determine the effects of three image-processing algorithms on diagnostic accuracy of digital mammography in comparison with conventional screen-film mammography. A total of 201 cases consisting of nonprocessed soft copy versions of the digital mammograms acquired from GE, Fischer, and Trex digital mammography systems (1997-1999) and conventional screen-film mammograms of the same patients were interpreted by nine radiologists. The raw digital data were processed with each of three different image-processing algorithms creating three presentations-manufacturer's default (applied and laser printed to film by each of the manufacturers), MUSICA, and PLAHE-were presented in soft copy display. There were three radiologists per presentation. Area under the receiver operating characteristic curve for GE digital mass cases was worse than screen-film for all digital presentations. The area under the receiver operating characteristic for Trex digital mass cases was better, but only with images processed with the manufacturer's default algorithm. Sensitivity for GE digital mass cases was worse than screen film for all digital presentations. Specificity for Fischer digital calcifications cases was worse than screen film for images processed in default and PLAHE algorithms. Specificity for Trex digital calcifications cases was worse than screen film for images processed with MUSICA. Specific image-processing algorithms may be necessary for optimal presentation for interpretation based on machine and lesion type.

Towards Knowledge Management for Smart Manufacturing.

PubMed

Feng, Shaw C; Bernstein, William Z; Hedberg, Thomas; Feeney, Allison Barnard

2017-09-01

The need for capturing knowledge in the digital form in design, process planning, production, and inspection has increasingly become an issue in manufacturing industries as the variety and complexity of product lifecycle applications increase. Both knowledge and data need to be well managed for quality assurance, lifecycle-impact assessment, and design improvement. Some technical barriers exist today that inhibit industry from fully utilizing design, planning, processing, and inspection knowledge. The primary barrier is a lack of a well-accepted mechanism that enables users to integrate data and knowledge. This paper prescribes knowledge management to address a lack of mechanisms for integrating, sharing, and updating domain-specific knowledge in smart manufacturing. Aspects of the knowledge constructs include conceptual design, detailed design, process planning, material property, production, and inspection. The main contribution of this paper is to provide a methodology on what knowledge manufacturing organizations access, update, and archive in the context of smart manufacturing. The case study in this paper provides some example knowledge objects to enable smart manufacturing.

Validation of a sterilization dose for products manufactured using a 3D printer

NASA Astrophysics Data System (ADS)

Wangsgard, Wendy; Winters, Martell

2018-02-01

As more healthcare products are personalized, the use of unique, patient-specific products will increase. Some of these are manufactured using a 3D printing process (also known as additive manufacturing) for either polymers or metals. For these products, processes such as sterilization validations must be handled in a different manner. The concepts typically used are still relevant but are approached from an alternative perspective to account for a potential production batch size of one, and for the great variability that can occur in size and shape of a product.

Technology CAD for integrated circuit fabrication technology development and technology transfer

NASA Astrophysics Data System (ADS)

Saha, Samar

2003-07-01

In this paper systematic simulation-based methodologies for integrated circuit (IC) manufacturing technology development and technology transfer are presented. In technology development, technology computer-aided design (TCAD) tools are used to optimize the device and process parameters to develop a new generation of IC manufacturing technology by reverse engineering from the target product specifications. While in technology transfer to manufacturing co-location, TCAD is used for process centering with respect to high-volume manufacturing equipment of the target manufacturing equipment of the target manufacturing facility. A quantitative model is developed to demonstrate the potential benefits of the simulation-based methodology in reducing the cycle time and cost of typical technology development and technology transfer projects over the traditional practices. The strategy for predictive simulation to improve the effectiveness of a TCAD-based project, is also discussed.

40 CFR 704.104 - Hexafluoropropylene oxide.

Code of Federal Regulations, 2010 CFR

2010-07-01

... CONTROL ACT REPORTING AND RECORDKEEPING REQUIREMENTS Chemical-Specific Reporting and Recordkeeping Rules... qualify as small for purposes of reporting on the processing of that chemical substance at that site...: (1) Persons who manufacture or propose to manufacture HFPO for use as an intermediate in the...

Closed-Loop Multitarget Optimization for Discovery of New Emulsion Polymerization Recipes

PubMed Central

2015-01-01

Self-optimization of chemical reactions enables faster optimization of reaction conditions or discovery of molecules with required target properties. The technology of self-optimization has been expanded to discovery of new process recipes for manufacture of complex functional products. A new machine-learning algorithm, specifically designed for multiobjective target optimization with an explicit aim to minimize the number of “expensive” experiments, guides the discovery process. This “black-box” approach assumes no a priori knowledge of chemical system and hence particularly suited to rapid development of processes to manufacture specialist low-volume, high-value products. The approach was demonstrated in discovery of process recipes for a semibatch emulsion copolymerization, targeting a specific particle size and full conversion. PMID:26435638

Integrated flexible manufacturing program for manufacturing automation and rapid prototyping

NASA Technical Reports Server (NTRS)

Brooks, S. L.; Brown, C. W.; King, M. S.; Simons, W. R.; Zimmerman, J. J.

1993-01-01

The Kansas City Division of Allied Signal Inc., as part of the Integrated Flexible Manufacturing Program (IFMP), is developing an integrated manufacturing environment. Several systems are being developed to produce standards and automation tools for specific activities within the manufacturing environment. The Advanced Manufacturing Development System (AMDS) is concentrating on information standards (STEP) and product data transfer; the Expert Cut Planner system (XCUT) is concentrating on machining operation process planning standards and automation capabilities; the Advanced Numerical Control system (ANC) is concentrating on NC data preparation standards and NC data generation tools; the Inspection Planning and Programming Expert system (IPPEX) is concentrating on inspection process planning, coordinate measuring machine (CMM) inspection standards and CMM part program generation tools; and the Intelligent Scheduling and Planning System (ISAPS) is concentrating on planning and scheduling tools for a flexible manufacturing system environment. All of these projects are working together to address information exchange, standardization, and information sharing to support rapid prototyping in a Flexible Manufacturing System (FMS) environment.

In situ manufacture of magnetic tunnel junctions by a direct-write process

NASA Astrophysics Data System (ADS)

Costanzi, Barry N.; Riazanova, Anastasia V.; Dan Dahlberg, E.; Belova, Lyubov M.

2014-06-01

In situ construction of Co/SiO2/Co magnetic tunnel junctions using direct-write electron-beam-induced deposition is described. Proof-of-concept devices were built layer by layer depositing the specific components one at a time, allowing device manufacture using a strictly additive process. The devices exhibit a magnetic tunneling signature which agrees qualitatively with the Slonczewski model of magnetic tunneling.

Numerical modeling of heat-transfer and the influence of process parameters on tailoring the grain morphology of IN718 in electron beam additive manufacturing

DOE PAGES

Raghavan, Narendran; Dehoff, Ryan; Pannala, Sreekanth; ...

2016-04-26

The fabrication of 3-D parts from CAD models by additive manufacturing (AM) is a disruptive technology that is transforming the metal manufacturing industry. The correlation between solidification microstructure and mechanical properties has been well understood in the casting and welding processes over the years. This paper focuses on extending these principles to additive manufacturing to understand the transient phenomena of repeated melting and solidification during electron beam powder melting process to achieve site-specific microstructure control within a fabricated component. In this paper, we have developed a novel melt scan strategy for electron beam melting of nickel-base superalloy (Inconel 718) andmore » also analyzed 3-D heat transfer conditions using a parallel numerical solidification code (Truchas) developed at Los Alamos National Laboratory. The spatial and temporal variations of temperature gradient (G) and growth velocity (R) at the liquid-solid interface of the melt pool were calculated as a function of electron beam parameters. By manipulating the relative number of voxels that lie in the columnar or equiaxed region, the crystallographic texture of the components can be controlled to an extent. The analysis of the parameters provided optimum processing conditions that will result in columnar to equiaxed transition (CET) during the solidification. Furthermore, the results from the numerical simulations were validated by experimental processing and characterization thereby proving the potential of additive manufacturing process to achieve site-specific crystallographic texture control within a fabricated component.« less

In vitro cytotoxicity and surface topography evaluation of additive manufacturing titanium implant materials.

PubMed

Tuomi, Jukka T; Björkstrand, Roy V; Pernu, Mikael L; Salmi, Mika V J; Huotilainen, Eero I; Wolff, Jan E H; Vallittu, Pekka K; Mäkitie, Antti A

2017-03-01

Custom-designed patient-specific implants and reconstruction plates are to date commonly manufactured using two different additive manufacturing (AM) technologies: direct metal laser sintering (DMLS) and electron beam melting (EBM). The purpose of this investigation was to characterize the surface structure and to assess the cytotoxicity of titanium alloys processed using DMLS and EBM technologies as the existing information on these issues is scarce. "Processed" and "polished" DMLS and EBM disks were assessed. Microscopic examination revealed titanium alloy particles and surface flaws on the processed materials. These surface flaws were subsequently removed by polishing. Surface roughness of EBM processed titanium was higher than that of DMLS processed. The cytotoxicity results of the DMLS and EBM discs were compared with a "gold standard" commercially available titanium mandible reconstruction plate. The mean cell viability for all discs was 82.6% (range, 77.4 to 89.7) and 83.3% for the control reconstruction plate. The DMLS and EBM manufactured titanium plates were non-cytotoxic both in "processed" and in "polished" forms.

Increasing component functionality via multi-process additive manufacturing

NASA Astrophysics Data System (ADS)

Coronel, Jose L.; Fehr, Katherine H.; Kelly, Dominic D.; Espalin, David; Wicker, Ryan B.

2017-05-01

Additively manufactured components, although extensively customizable, are often limited in functionality. Multi-process additive manufacturing (AM) grants the ability to increase the functionality of components via subtractive manufacturing, wire embedding, foil embedding and pick and place. These processes are scalable to include several platforms ranging from desktop to large area printers. The Multi3D System is highlighted, possessing the capability to perform the above mentioned processes, all while transferring a fabricated component with a robotic arm. Work was conducted to fabricate a patent inspired, printed missile seeker. The seeker demonstrated the advantage of multi-process AM via introduction of the pick and place process. Wire embedding was also explored, with the successful interconnect of two layers of embedded wires in different planes. A final demonstration of a printed contour bracket, served to show the reduction of surface roughness on a printed part is 87.5% when subtractive manufacturing is implemented in tandem with AM. Functionality of the components on all the cases was improved. Results included optical components embedded within the printed housing, wires embedded with interconnection, and reduced surface roughness. These results highlight the improved functionality of components through multi-process AM, specifically through work conducted with the Multi3D System.

Spray-congealed microparticles for drug delivery - an overview of factors influencing their production and characteristics.

PubMed

Oh, Ching Mien; Guo, Qiyun; Wan Sia Heng, Paul; Chan, Lai Wah

2014-07-01

In any manufacturing process, the success of producing an end product with the desired properties and yield depends on a range of factors that include the equipment, process and formulation variables. It is the interest of manufacturers and researchers to understand each manufacturing process better and ascertain the effects of various manufacturing-associated factors on the properties of the end product. Unless the manufacturing process is well understood, it would be difficult to set realistic limits for the process variables and raw material specifications to ensure consistently high-quality and reproducible end products. Over the years, spray congealing has been used to produce particulates by the food and pharmaceutical industries. The latter have used this technology to develop specialized drug delivery systems. In this review, basic principles as well as advantages and disadvantages of the spray congealing process will be covered. Recent developments in spray congealing equipment, process variables and formulation variables such as the matrix material, encapsulated material and additives will also be discussed. Innovative equipment designs and formulations for spray congealing have emerged. Judicious choice of atomizers, polymers and additives is the key to achieve the desired properties of the microparticles for drug delivery.

Application of pulsed-field gel electrophoresis to characterise and trace the prevalence of Enterobacter sakazakii in an infant formula processing facility.

PubMed

Mullane, N R; Whyte, P; Wall, P G; Quinn, T; Fanning, S

2007-05-01

Enterobacter sakazakii (E. sakazakii) contamination of powdered infant formula (PIF) and its processing environment was monitored between April 2005 and March 2006. The purpose of the monitoring programme was to locate points of contamination, investigate clonal persistence, and identify possible dissemination routes along the processing chain. A total of 80 E. sakazakii isolates were recovered from the manufacturing facility. The overall frequency of isolation of E. sakazakii in intermediate and final product was 2.5%, while specific locations in the processing environment were contaminated at frequencies up to 31%. All E. sakazakii isolates were characterised by pulsed-field gel electrophoresis (PFGE). XbaI macrorestriction digests yielded 19 unique pulse-types that could be grouped into 6 clusters of between 5 and 32 isolates. The formation of large clusters was consistent with the presence of a number of clones in the manufacturing environment. While the majority of isolates were of environmental origin (72.5%), no cluster was confined to one specific location and indistinguishable PFGE profiles were generated from isolates cultured from the manufacturing environment, sampling points along the processing chain and from intermediate and final product. These findings suggest that the manufacturing environment serves as a key route for sporadic contamination of PIF. These data will support the development of efficient intervention measures contributing to the reduction of E. sakazakii in the PIF processing chain.

A Database Approach to Computer Integrated Manufacturing

DTIC Science & Technology

1988-06-01

advanced application areas such as tactical weapons systems, industrial manufacturing systems, and -D, ........... . . .m - I I [ l~ ii i l I4...manufacturing industry . We will provide definitions for the functions which are most prevalent in our research. Figure 3 shows the basic processes partitioned...IGES) [Ref. 9] and the Product Definition Data Interface (PDDI) [Ref. 101. 11 The IGES specification is considered an industry standard for the

Practical LCA for short shelf life products

NASA Astrophysics Data System (ADS)

Laurin, Lise; Goedkoop, Mark; Norris, Greg

2005-11-01

Manufacturers in many of today's industries are faced with product shelf life counted in months. Traditionally, this has made it very difficult to make a life cycle assessment (LCA) of a product, since the product would be obsolete by the time the LCA was completed. A new concept in LCA that allows specialists in things other than LCA to rapidly create both a model and generate "what-if" scenarios will allow even manufacturers of short shelf life products take advantage of the benefits of LCA. These industry-specific "wizards" are built around a manufacturing process and can be rapidly updated or customized to a particular manufacturer or process type. Results can be used internally for decision-making and can also enable manufacturers submit information for environmentally preferable purchasing, eco-labels, etc.

Development and demonstration of manufacturing processes for fabricating graphite/LARC 160 polyimide structural elements

NASA Technical Reports Server (NTRS)

Frost, R. K.; Jones, J. S.; Dynes, P. J.; Wykes, D. H.

1981-01-01

The development and demonstration of manufacturing technologies for the structural application of Celion graphite/LARC-160 polyimide composite material is discussed. Process development and fabrication of demonstration components are discussed. Process development included establishing quality assurance of the basic composite material and processing, nondestructive inspection of fabricated components, developing processes for specific structural forms, and qualification of processes through mechanical testing. Demonstration components were fabricated. The demonstration components consisted of flat laminates, skin/stringer panels, honeycomb panels, chopped fiber compression moldings, and a technology demonstrator segment (TDS) representative of the space shuttle aft body flap.

40 CFR 704.25 - 11-Aminoundecanoic acid.

Code of Federal Regulations, 2010 CFR

2010-07-01

... CONTROL ACT REPORTING AND RECORDKEEPING REQUIREMENTS Chemical-Specific Reporting and Recordkeeping Rules... not qualify as small for purposes of reporting on the processing of that chemical substance at that... section: (1) Persons who manufacture or propose to manufacture 11-AA: (i) For use as an intermediate in...

40 CFR 461.2 - General definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... STANDARDS (CONTINUED) BATTERY MANUFACTURING POINT SOURCE CATEGORY General Provisions § 461.2 General... this part: (a) “Battery” means a modular electric power source where part or all of the fuel is... and a battery. (b) “Battery manufacturing operations” means all of the specific processes used to...

40 CFR 461.2 - General definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... STANDARDS (CONTINUED) BATTERY MANUFACTURING POINT SOURCE CATEGORY General Provisions § 461.2 General... this part: (a) “Battery” means a modular electric power source where part or all of the fuel is... and a battery. (b) “Battery manufacturing operations” means all of the specific processes used to...

40 CFR 461.2 - General definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... STANDARDS (CONTINUED) BATTERY MANUFACTURING POINT SOURCE CATEGORY General Provisions § 461.2 General... this part: (a) “Battery” means a modular electric power source where part or all of the fuel is... and a battery. (b) “Battery manufacturing operations” means all of the specific processes used to...

Just-in-time Design and Additive Manufacture of Patient-specific Medical Implants

NASA Astrophysics Data System (ADS)

Shidid, Darpan; Leary, Martin; Choong, Peter; Brandt, Milan

Recent advances in medical imaging and manufacturing science have enabled the design and production of complex, patient-specific orthopaedic implants. Additive Manufacture (AM) generates three-dimensional structures layer by layer, and is not subject to the constraints associated with traditional manufacturing methods. AM provides significant opportunities for the design of novel geometries and complex lattice structures with enhanced functional performance. However, the design and manufacture of patient-specific AM implant structures requires unique expertise in handling various optimization platforms. Furthermore, the design process for complex structures is computationally intensive. The primary aim of this research is to enable the just-in-time customisation of AM prosthesis; whereby AM implant design and manufacture be completed within the time constraints of a single surgical procedure, while minimising prosthesis mass and optimising the lattice structure to match the stiffness of the surrounding bone tissue. In this research, a design approach using raw CT scan data is applied to the AM manufacture of femoral prosthesis. Using the proposed just-in-time concept, the mass of the prosthesis was rapidly designed and manufactured while satisfying the associated structural requirements. Compressive testing of lattice structures manufactured using proposed method shows that the load carrying capacity of the resected composite bone can be recovered by up to 85% and the compressive stiffness of the AM prosthesis is statistically indistinguishable from the stiffness of the initial bone.

Craniofacial Reconstruction by a Cost-Efficient Template-Based Process Using 3D Printing

PubMed Central

Beiglboeck, Fabian; Honigmann, Philipp; Jaquiéry, Claude; Thieringer, Florian

2017-01-01

Summary: Craniofacial defects often result in aesthetic and functional deficits, which affect the patient’s psyche and wellbeing. Patient-specific implants remain the optimal solution, but their use is limited or impractical due to their high costs. This article describes a fast and cost-efficient workflow of in-house manufactured patient-specific implants for craniofacial reconstruction and cranioplasty. As a proof of concept, we present a case of reconstruction of a craniofacial defect with involvement of the supraorbital rim. The following hybrid manufacturing process combines additive manufacturing with silicone molding and an intraoperative, manual fabrication process. A computer-aided design template is 3D printed from thermoplastics by a fused deposition modeling 3D printer and then silicone molded manually. After sterilization of the patient-specific mold, it is used intraoperatively to produce an implant from polymethylmethacrylate. Due to the combination of these 2 straightforward processes, the procedure can be kept very simple, and no advanced equipment is needed, resulting in minimal financial expenses. The whole fabrication of the mold is performed within approximately 2 hours depending on the template’s size and volume. This reliable technique is easy to adopt and suitable for every health facility, especially those with limited financial resources in less privileged countries, enabling many more patients to profit from patient-specific treatment. PMID:29263977

Additive Manufacturing of Nickel Superalloys: Opportunities for Innovation and Challenges Related to Qualification

NASA Astrophysics Data System (ADS)

Babu, S. S.; Raghavan, N.; Raplee, J.; Foster, S. J.; Frederick, C.; Haines, M.; Dinwiddie, R.; Kirka, M. K.; Plotkowski, A.; Lee, Y.; Dehoff, R. R.

2018-06-01

Innovative designs for turbines can be achieved by advances in nickel-based superalloys and manufacturing methods, including the adoption of additive manufacturing. In this regard, selective electron beam melting (SEBM) and selective laser melting (SLM) of nickel-based superalloys do provide distinct advantages. Furthermore, the direct energy deposition (DED) processes can be used for repair and reclamation of nickel alloy components. The current paper explores opportunities for innovation and qualification challenges with respect to deployment of AM as a disruptive manufacturing technology. In the first part of the paper, fundamental correlations of processing parameters to defect tendency and microstructure evolution will be explored using DED process. In the second part of the paper, opportunities for innovation in terms of site-specific control of microstructure during processing will be discussed. In the third part of the paper, challenges in qualification of AM parts for service will be discussed and potential methods to alleviate these issues through in situ process monitoring, and big data analytics are proposed.

Method for indexing and retrieving manufacturing-specific digital imagery based on image content

DOEpatents

Ferrell, Regina K.; Karnowski, Thomas P.; Tobin, Jr., Kenneth W.

2004-06-15

A method for indexing and retrieving manufacturing-specific digital images based on image content comprises three steps. First, at least one feature vector can be extracted from a manufacturing-specific digital image stored in an image database. In particular, each extracted feature vector corresponds to a particular characteristic of the manufacturing-specific digital image, for instance, a digital image modality and overall characteristic, a substrate/background characteristic, and an anomaly/defect characteristic. Notably, the extracting step includes generating a defect mask using a detection process. Second, using an unsupervised clustering method, each extracted feature vector can be indexed in a hierarchical search tree. Third, a manufacturing-specific digital image associated with a feature vector stored in the hierarchicial search tree can be retrieved, wherein the manufacturing-specific digital image has image content comparably related to the image content of the query image. More particularly, can include two data reductions, the first performed based upon a query vector extracted from a query image. Subsequently, a user can select relevant images resulting from the first data reduction. From the selection, a prototype vector can be calculated, from which a second-level data reduction can be performed. The second-level data reduction can result in a subset of feature vectors comparable to the prototype vector, and further comparable to the query vector. An additional fourth step can include managing the hierarchical search tree by substituting a vector average for several redundant feature vectors encapsulated by nodes in the hierarchical search tree.

Concise Review: Guidance in Developing Commercializable Autologous/Patient-Specific Cell Therapy Manufacturing

PubMed Central

Armant, Myriam; Brandwein, Harvey; Burger, Scott; Campbell, Andrew; Carpenito, Carmine; Clarke, Dominic; Fong, Timothy; Karnieli, Ohad; Niss, Knut; Van't Hof, Wouter; Wagey, Ravenska

2013-01-01

Cell therapy is poised to play an enormous role in regenerative medicine. However, little guidance is being made available to academic and industrial entities in the start-up phase. In this technical review, members of the International Society for Cell Therapy provide guidance in developing commercializable autologous and patient-specific manufacturing strategies from the perspective of process development. Special emphasis is placed on providing guidance to small academic or biotech researchers as to what simple questions can be addressed or answered at the bench in order to make their cell therapy products more feasible for commercial-scale production. We discuss the processes that are required for scale-out at the manufacturing level, and how many questions can be addressed at the bench level. The goal of this review is to provide guidance in the form of topics that can be addressed early in the process of development to better the chances of the product being successful for future commercialization. PMID:24101671

7 CFR 58.735 - Quality specifications for raw materials.

Code of Federal Regulations, 2014 CFR

2014-01-01

... specifications of the finished product. (b) Swiss. Swiss cheese used in the manufacture of pasteurized process... Swiss cheese. (d) Cream cheese, Neufchatel cheese. Mixed with other foods, or used for spreads and dips... Service 1 Requirements for Processed Cheese Products Bearing Usda Official Identification § 58.735 Quality...

7 CFR 58.735 - Quality specifications for raw materials.

Code of Federal Regulations, 2013 CFR

2013-01-01

... specifications of the finished product. (b) Swiss. Swiss cheese used in the manufacture of pasteurized process... Swiss cheese. (d) Cream cheese, Neufchatel cheese. Mixed with other foods, or used for spreads and dips... Service 1 Requirements for Processed Cheese Products Bearing Usda Official Identification § 58.735 Quality...

7 CFR 58.735 - Quality specifications for raw materials.

Code of Federal Regulations, 2012 CFR

2012-01-01

... specifications of the finished product. (b) Swiss. Swiss cheese used in the manufacture of pasteurized process... Swiss cheese. (d) Cream cheese, Neufchatel cheese. Mixed with other foods, or used for spreads and dips... Service 1 Requirements for Processed Cheese Products Bearing Usda Official Identification § 58.735 Quality...

49 CFR 178.35 - General requirements for specification cylinders.

Code of Federal Regulations, 2011 CFR

2011-10-01

... cylinders made by the billet-piercing process, billets must be inspected and shown to be free from pipe... specific construction design.); (v) Witnessing all tests; (vi) Verify threads by gauge; (vii) Reporting... certifies that the processes of manufacture and heat treatment of cylinders were observed and found...

49 CFR 178.35 - General requirements for specification cylinders.

Code of Federal Regulations, 2014 CFR

2014-10-01

... cylinders made by the billet-piercing process, billets must be inspected and shown to be free from pipe... specific construction design.); (v) Witnessing all tests; (vi) Verify threads by gauge; (vii) Reporting... certifies that the processes of manufacture and heat treatment of cylinders were observed and found...

49 CFR 178.35 - General requirements for specification cylinders.

Code of Federal Regulations, 2013 CFR

2013-10-01

... cylinders made by the billet-piercing process, billets must be inspected and shown to be free from pipe... specific construction design.); (v) Witnessing all tests; (vi) Verify threads by gauge; (vii) Reporting... certifies that the processes of manufacture and heat treatment of cylinders were observed and found...

49 CFR 178.35 - General requirements for specification cylinders.

Code of Federal Regulations, 2012 CFR

2012-10-01

... cylinders made by the billet-piercing process, billets must be inspected and shown to be free from pipe... specific construction design.); (v) Witnessing all tests; (vi) Verify threads by gauge; (vii) Reporting... certifies that the processes of manufacture and heat treatment of cylinders were observed and found...

49 CFR 178.38 - Specification 3B seamless steel cylinders.

Code of Federal Regulations, 2012 CFR

2012-10-01

... the heat number. (d) Manufacture. Cylinders must be manufactured using equipment and processes... plugs, etc.) for those openings. Threads, conforming to the following, are required on all openings: (1) Threads must be clean cut, even, without checks, and to gauge. (2) Taper threads when used, must be of a...

49 CFR 178.38 - Specification 3B seamless steel cylinders.

Code of Federal Regulations, 2010 CFR

2010-10-01

... the heat number. (d) Manufacture. Cylinders must be manufactured using equipment and processes... plugs, etc.) for those openings. Threads, conforming to the following, are required on all openings: (1) Threads must be clean cut, even, without checks, and to gauge. (2) Taper threads when used, must be of a...

49 CFR 178.44 - Specification 3HT seamless steel cylinders for aircraft use.

Code of Federal Regulations, 2013 CFR

2013-10-01

... cylinder. (d) Manufacture. Cylinders must be manufactured using equipment and processes adequate to ensure.... (h) Openings in cylinders and connections (valves, fuse plugs, etc.) for those openings. Threads conforming to the following are required on openings: (1) Threads must be clean cut, even, without cracks...

49 CFR 178.38 - Specification 3B seamless steel cylinders.

Code of Federal Regulations, 2013 CFR

2013-10-01

... the heat number. (d) Manufacture. Cylinders must be manufactured using equipment and processes... plugs, etc.) for those openings. Threads, conforming to the following, are required on all openings: (1) Threads must be clean cut, even, without checks, and to gauge. (2) Taper threads when used, must be of a...

49 CFR 178.44 - Specification 3HT seamless steel cylinders for aircraft use.

Code of Federal Regulations, 2012 CFR

2012-10-01

... cylinder. (d) Manufacture. Cylinders must be manufactured using equipment and processes adequate to ensure.... (h) Openings in cylinders and connections (valves, fuse plugs, etc.) for those openings. Threads conforming to the following are required on openings: (1) Threads must be clean cut, even, without cracks...

49 CFR 178.38 - Specification 3B seamless steel cylinders.

Code of Federal Regulations, 2014 CFR

2014-10-01

... the heat number. (d) Manufacture. Cylinders must be manufactured using equipment and processes... plugs, etc.) for those openings. Threads, conforming to the following, are required on all openings: (1) Threads must be clean cut, even, without checks, and to gauge. (2) Taper threads when used, must be of a...

49 CFR 178.44 - Specification 3HT seamless steel cylinders for aircraft use.

Code of Federal Regulations, 2014 CFR

2014-10-01

... cylinder. (d) Manufacture. Cylinders must be manufactured using equipment and processes adequate to ensure.... (h) Openings in cylinders and connections (valves, fuse plugs, etc.) for those openings. Threads conforming to the following are required on openings: (1) Threads must be clean cut, even, without cracks...

Advanced Near Net Shape Technology

NASA Technical Reports Server (NTRS)

Vickers, John

2015-01-01

The objective of the Advanced Near Net Shape Technology (ANNST) project is to radically improve near net shape manufacturing methods from the current Technology/ Manufacturing Readiness Levels (TRL/MRL 3-4) to the point where they are viable candidates (TRL/ MRL-6) for shortening the time and cost for insertion of new aluminum alloys and revolutionary manufacturing methods into the development/improvement of space structures. Conventional cyrotank manufacturing processes require fabrication of multiple pieces welded together to form a complete tank. A variety of near net shape manufacturing processes has demonstrated excellent potential for enabling single-piece construction of components such as domes, barrels, and ring frames. Utilization of such processes can dramatically reduce the extent of welding and joining needed to construct cryogenic tanks and other aerospace structures. The specific focus of this project is to successfully mature the integrally stiffened cylinder (ISC) process in which a single-piece cylinder with integral stiffeners is formed in one spin/flow forming process. Structural launch vehicle components, like cryogenic fuel tanks (e.g., space shuttle external tank), are currently fabricated via multipiece assembly of parts produced through subtractive manufacturing techniques. Stiffened structural panels are heavily machined from thick plate, which results in excessive scrap rates. Multipiece construction requires welds to assemble the structure, which increases the risk for defects and catastrophic failures.

Selective laser melting of Inconel super alloy-a review

NASA Astrophysics Data System (ADS)

Karia, M. C.; Popat, M. A.; Sangani, K. B.

2017-07-01

Additive manufacturing is a relatively young technology that uses the principle of layer by layer addition of material in solid, liquid or powder form to develop a component or product. The quality of additive manufactured part is one of the challenges to be addressed. Researchers are continuously working at various levels of additive manufacturing technologies. One of the significant powder bed processes for met als is Selective Laser Melting (SLM). Laser based processes are finding more attention of researchers and industrial world. The potential of this technique is yet to be fully explored. Due to very high strength and creep resistance Inconel is extensively used nickel based super alloy for manufacturing components for aerospace, automobile and nuclear industries. Due to law content of Aluminum and Titanium, it exhibits good fabricability too. Therefore the alloy is ideally suitable for selective laser melting to manufacture intricate components with high strength requirements. The selection of suitable process for manufacturing for a specific component depends on geometrical complexity, production quantity, and cost and required strength. There are numerous researchers working on various aspects like metallurgical and micro structural investigations and mechanical properties, geometrical accuracy, effects of process parameters and its optimization and mathematical modeling etc. The present paper represents a comprehensive overview of selective laser melting process for Inconel group of alloys.

Validation of the manufacturing process used to produce long-acting recombinant factor IX Fc fusion protein

PubMed Central

McCue, J; Osborne, D; Dumont, J; Peters, R; Mei, B; Pierce, G F; Kobayashi, K; Euwart, D

2014-01-01

Recombinant factor IX Fc (rFIXFc) fusion protein is the first of a new class of bioengineered long-acting factors approved for the treatment and prevention of bleeding episodes in haemophilia B. The aim of this work was to describe the manufacturing process for rFIXFc, to assess product quality and to evaluate the capacity of the process to remove impurities and viruses. This manufacturing process utilized a transferable and scalable platform approach established for therapeutic antibody manufacturing and adapted for production of the rFIXFc molecule. rFIXFc was produced using a process free of human- and animal-derived raw materials and a host cell line derived from human embryonic kidney (HEK) 293H cells. The process employed multi-step purification and viral clearance processing, including use of a protein A affinity capture chromatography step, which binds to the Fc portion of the rFIXFc molecule with high affinity and specificity, and a 15 nm pore size virus removal nanofilter. Process validation studies were performed to evaluate identity, purity, activity and safety. The manufacturing process produced rFIXFc with consistent product quality and high purity. Impurity clearance validation studies demonstrated robust and reproducible removal of process-related impurities and adventitious viruses. The rFIXFc manufacturing process produces a highly pure product, free of non-human glycan structures. Validation studies demonstrate that this product is produced with consistent quality and purity. In addition, the scalability and transferability of this process are key attributes to ensure consistent and continuous supply of rFIXFc. PMID:24811361

Mechanical strength of welding zones produced by material extrusion additive manufacturing.

PubMed

Davis, Chelsea S; Hillgartner, Kaitlyn E; Han, Seung Hoon; Seppala, Jonathan E

2017-08-01

As more manufacturing processes and research institutions adopt customized manufacturing as a key element in their design strategies and finished products, the resulting mechanical properties of parts produced through additive manufacturing (AM) must be characterized and understood. In material extrusion (MatEx), the most recently extruded polymer filament must bond to the previously extruded filament via polymer diffusion to form a "weld". The strength of the weld limits the performance of the manufactured part and is controlled through processing conditions. Under-standing the role of processing conditions, specifically extruder velocity and extruder temperature, on the overall strength of the weld will allow optimization of MatEx-AM parts. Here, the fracture toughness of a single weld is determined through a facile "trouser tear" Mode III fracture experiment. The actual weld thickness is observed directly by optical microscopy characterization of cross sections of MatEx-AM samples. Representative data of weld strength as a function of printing parameters on a commercial 3D printer demonstrates the robustness of the method.

Recent advances in the reconstruction of cranio-maxillofacial defects using computer-aided design/computer-aided manufacturing.

PubMed

Oh, Ji-Hyeon

2018-12-01

With the development of computer-aided design/computer-aided manufacturing (CAD/CAM) technology, it has been possible to reconstruct the cranio-maxillofacial defect with more accurate preoperative planning, precise patient-specific implants (PSIs), and shorter operation times. The manufacturing processes include subtractive manufacturing and additive manufacturing and should be selected in consideration of the material type, available technology, post-processing, accuracy, lead time, properties, and surface quality. Materials such as titanium, polyethylene, polyetheretherketone (PEEK), hydroxyapatite (HA), poly-DL-lactic acid (PDLLA), polylactide-co-glycolide acid (PLGA), and calcium phosphate are used. Design methods for the reconstruction of cranio-maxillofacial defects include the use of a pre-operative model printed with pre-operative data, printing a cutting guide or template after virtual surgery, a model after virtual surgery printed with reconstructed data using a mirror image, and manufacturing PSIs by directly obtaining PSI data after reconstruction using a mirror image. By selecting the appropriate design method, manufacturing process, and implant material according to the case, it is possible to obtain a more accurate surgical procedure, reduced operation time, the prevention of various complications that can occur using the traditional method, and predictive results compared to the traditional method.

Mining manufacturing data for discovery of high productivity process characteristics.

PubMed

Charaniya, Salim; Le, Huong; Rangwala, Huzefa; Mills, Keri; Johnson, Kevin; Karypis, George; Hu, Wei-Shou

2010-06-01

Modern manufacturing facilities for bioproducts are highly automated with advanced process monitoring and data archiving systems. The time dynamics of hundreds of process parameters and outcome variables over a large number of production runs are archived in the data warehouse. This vast amount of data is a vital resource to comprehend the complex characteristics of bioprocesses and enhance production robustness. Cell culture process data from 108 'trains' comprising production as well as inoculum bioreactors from Genentech's manufacturing facility were investigated. Each run constitutes over one-hundred on-line and off-line temporal parameters. A kernel-based approach combined with a maximum margin-based support vector regression algorithm was used to integrate all the process parameters and develop predictive models for a key cell culture performance parameter. The model was also used to identify and rank process parameters according to their relevance in predicting process outcome. Evaluation of cell culture stage-specific models indicates that production performance can be reliably predicted days prior to harvest. Strong associations between several temporal parameters at various manufacturing stages and final process outcome were uncovered. This model-based data mining represents an important step forward in establishing a process data-driven knowledge discovery in bioprocesses. Implementation of this methodology on the manufacturing floor can facilitate a real-time decision making process and thereby improve the robustness of large scale bioprocesses. 2010 Elsevier B.V. All rights reserved.

A Digital Methodology for the Design Process of Aerospace Assemblies with Sustainable Composite Processes & Manufacture

NASA Astrophysics Data System (ADS)

McEwan, W.; Butterfield, J.

2011-05-01

The well established benefits of composite materials are driving a significant shift in design and manufacture strategies for original equipment manufacturers (OEMs). Thermoplastic composites have advantages over the traditional thermosetting materials with regards to sustainability and environmental impact, features which are becoming increasingly pertinent in the aerospace arena. However, when sustainability and environmental impact are considered as design drivers, integrated methods for part design and product development must be developed so that any benefits of sustainable composite material systems can be assessed during the design process. These methods must include mechanisms to account for process induced part variation and techniques related to re-forming, recycling and decommissioning, which are in their infancy. It is proposed in this paper that predictive techniques related to material specification, part processing and product cost of thermoplastic composite components, be integrated within a Through Life Management (TLM) product development methodology as part of a larger strategy of product system modeling to improve disciplinary concurrency, realistic part performance, and to place sustainability at the heart of the design process. This paper reports the enhancement of digital manufacturing tools as a means of drawing simulated part manufacturing scenarios, real time costing mechanisms, and broader lifecycle performance data capture into the design cycle. The work demonstrates predictive processes for sustainable composite product manufacture and how a Product-Process-Resource (PPR) structure can be customised and enhanced to include design intent driven by `Real' part geometry and consequent assembly. your paper.

Additive Manufacturing Design Considerations for Liquid Engine Components

NASA Technical Reports Server (NTRS)

Whitten, Dave; Hissam, Andy; Baker, Kevin; Rice, Darron

2014-01-01

The Marshall Space Flight Center's Propulsion Systems Department has gained significant experience in the last year designing, building, and testing liquid engine components using additive manufacturing. The department has developed valve, duct, turbo-machinery, and combustion device components using this technology. Many valuable lessons were learned during this process. These lessons will be the focus of this presentation. We will present criteria for selecting part candidates for additive manufacturing. Some part characteristics are 'tailor made' for this process. Selecting the right parts for the process is the first step to maximizing productivity gains. We will also present specific lessons we learned about feature geometry that can and cannot be produced using additive manufacturing machines. Most liquid engine components were made using a two-step process. The base part was made using additive manufacturing and then traditional machining processes were used to produce the final part. The presentation will describe design accommodations needed to make the base part and lessons we learned about which features could be built directly and which require the final machine process. Tolerance capabilities, surface finish, and material thickness allowances will also be covered. Additive Manufacturing can produce internal passages that cannot be made using traditional approaches. It can also eliminate a significant amount of manpower by reducing part count and leveraging model-based design and analysis techniques. Information will be shared about performance enhancements and design efficiencies we experienced for certain categories of engine parts.

Scale-up of 2G wire manufacturing at American Superconductor Corporation

NASA Astrophysics Data System (ADS)

Fleshler, S.; Buczek, D.; Carter, B.; Cedrone, P.; DeMoranville, K.; Gannon, J.; Inch, J.; Li, X.; Lynch, J.; Otto, A.; Podtburg, E.; Roy, D.; Rupich, M.; Sathyamurthy, S.; Schreiber, J.; Thieme, C.; Thompson, E.; Tucker, D.; Nagashima, K.; Ogata, M.

2009-10-01

American Superconductor Corporation (AMSC) has developed the base technology and a manufacturing line for initial volume production of low-cost second generation high temperature superconductor (2G HTS) wire for commercial and military applications. The manufacturing line is based on reel-to-reel processing of wide HTS strips using rolling assisted bi-axially textured substrate (RABiTS™) for the template and Metal Organic Deposition (MOD) for the HTS layer. AMSC’s wide strip process is a low cost manufacturing technology since multiple wires are produced in a single manufacturing pass by slitting the wide strip to narrower width in the last stage of the manufacturing process. Industry standard 4.4 mm wide wires are produced by laminating metallic foils, such as copper, stainless steel or any other material, to the HTS insert wire, and are chosen to tailor the electrical, thermal and mechanical properties of the wire for specific applications. The laminated, 4.4 mm wide wires are known as “344 superconductors.” In this paper, we summarize the status of AMSC’s manufacturing capability, the performance of the wire presently being produced, as well as the cost and technical advantages of AMSC’s manufacturing approach. In addition, future direction for research and development to improve electrical performance is presented.

The Future of Pharmaceutical Manufacturing Sciences

PubMed Central

2015-01-01

The entire pharmaceutical sector is in an urgent need of both innovative technological solutions and fundamental scientific work, enabling the production of highly engineered drug products. Commercial‐scale manufacturing of complex drug delivery systems (DDSs) using the existing technologies is challenging. This review covers important elements of manufacturing sciences, beginning with risk management strategies and design of experiments (DoE) techniques. Experimental techniques should, where possible, be supported by computational approaches. With that regard, state‐of‐art mechanistic process modeling techniques are described in detail. Implementation of materials science tools paves the way to molecular‐based processing of future DDSs. A snapshot of some of the existing tools is presented. Additionally, general engineering principles are discussed covering process measurement and process control solutions. Last part of the review addresses future manufacturing solutions, covering continuous processing and, specifically, hot‐melt processing and printing‐based technologies. Finally, challenges related to implementing these technologies as a part of future health care systems are discussed. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3612–3638, 2015 PMID:26280993

The Future of Pharmaceutical Manufacturing Sciences.

PubMed

Rantanen, Jukka; Khinast, Johannes

2015-11-01

The entire pharmaceutical sector is in an urgent need of both innovative technological solutions and fundamental scientific work, enabling the production of highly engineered drug products. Commercial-scale manufacturing of complex drug delivery systems (DDSs) using the existing technologies is challenging. This review covers important elements of manufacturing sciences, beginning with risk management strategies and design of experiments (DoE) techniques. Experimental techniques should, where possible, be supported by computational approaches. With that regard, state-of-art mechanistic process modeling techniques are described in detail. Implementation of materials science tools paves the way to molecular-based processing of future DDSs. A snapshot of some of the existing tools is presented. Additionally, general engineering principles are discussed covering process measurement and process control solutions. Last part of the review addresses future manufacturing solutions, covering continuous processing and, specifically, hot-melt processing and printing-based technologies. Finally, challenges related to implementing these technologies as a part of future health care systems are discussed. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association.

40 CFR Appendix F to Subpart B of... - Standard for Recover-Only Equipment That Extracts a Single, Specific Refrigerant Other Than CFC...

Code of Federal Regulations, 2013 CFR

2013-07-01

... refrigerant, which are either (1) to be returned to a refrigerant reclamation facility that will process the... capability is required which shall process contaminated refrigerant samples at specific temperatures. 6.2The... the recovery process to ±2% of the original manufacturer's formulation submitted to, and accepted by...

40 CFR Appendix F to Subpart B of... - Standard for Recover-Only Equipment That Extracts a Single, Specific Refrigerant Other Than CFC...

Code of Federal Regulations, 2010 CFR

2010-07-01

... refrigerant, which are either (1) to be returned to a refrigerant reclamation facility that will process the... capability is required which shall process contaminated refrigerant samples at specific temperatures. 6.2The... the recovery process to ±2% of the original manufacturer's formulation submitted to, and accepted by...

40 CFR Appendix F to Subpart B of... - Standard for Recover-Only Equipment That Extracts a Single, Specific Refrigerant Other Than CFC...

Code of Federal Regulations, 2011 CFR

2011-07-01

... refrigerant, which are either (1) to be returned to a refrigerant reclamation facility that will process the... capability is required which shall process contaminated refrigerant samples at specific temperatures. 6.2The... the recovery process to ±2% of the original manufacturer's formulation submitted to, and accepted by...

40 CFR Appendix F to Subpart B of... - Standard for Recover-Only Equipment That Extracts a Single, Specific Refrigerant Other Than CFC...

Code of Federal Regulations, 2012 CFR

2012-07-01

... refrigerant, which are either (1) to be returned to a refrigerant reclamation facility that will process the... capability is required which shall process contaminated refrigerant samples at specific temperatures. 6.2The... the recovery process to ±2% of the original manufacturer's formulation submitted to, and accepted by...

40 CFR Appendix F to Subpart B of... - Standard for Recover-Only Equipment That Extracts a Single, Specific Refrigerant Other Than CFC...

Code of Federal Regulations, 2014 CFR

2014-07-01

... refrigerant, which are either (1) to be returned to a refrigerant reclamation facility that will process the... capability is required which shall process contaminated refrigerant samples at specific temperatures. 6.2The... the recovery process to ±2% of the original manufacturer's formulation submitted to, and accepted by...

Considerations on the construction of a Powder Bed Fusion platform for Additive Manufacturing

NASA Astrophysics Data System (ADS)

Andersen, Sebastian Aagaard; Nielsen, Karl-Emil; Pedersen, David Bue; Nielsen, Jakob Skov

As the demand for moulds and other tools becomes increasingly specific and complex, an additive manufacturing approach to production is making its way to the industry through laser based consolidation of metal powder particles by a method known as powder bed fusion. This paper concerns a variety of design choices facilitating the development of an experimental powder bed fusion machine tool, capable of manufacturing metal parts with strength matching that of conventional manufactured parts and a complexity surpassing that of subtractive processes. To understand the different mechanisms acting within such an experimental machine tool, a fully open and customizable rig is constructed. Emphasizing modularity in the rig, allows alternation of lasers, scanner systems, optical elements, powder deposition, layer height, temperature, atmosphere, and powder type. Through a custom-made software platform, control of the process is achieved, which extends into a graphical user interface, easing adjustment of process parameters and the job file generation.

ANSI/AIAA S-081A, Pressure Vessel Standards Implementation Guidelines

NASA Technical Reports Server (NTRS)

Greene, Nathanael J.

2009-01-01

The stress rupture specification for Composite Overwrapped Pressure Vessels (COPV) is discussed. The composite shell of the COPV shall be designed to meet the design life considering the time it is under sustained load. A Mechcanical Damage Control Plan (MDCP) shall be created and implemented that assures the COPV will not fail due to mechanical damage due to manufacturing, testing, shipping, installation, or flight. Proven processes and procedures for fabrication and repair shall be used to preclude damage or material degradation during material processing, manufacturing operations, and refurbushment.Selected NDI techniques for the liner and/or boss(es) shall be performed before overwrapping with composite. When visual inspection reveals mechanical damage or defects exceeding manufacturing specification levels (and standard repair procedures), the damaged COPV shall be submitted to a material review board (MRB) for disposition. Every COPV shall be subjected to visual and other non-destructive inspection (NDI), per the inspection plan.

Thermodynamic analysis of resources used in manufacturing processes.

PubMed

Gutowski, Timothy G; Branham, Matthew S; Dahmus, Jeffrey B; Jones, Alissa J; Thiriez, Alexandre

2009-03-01

In this study we use a thermodynamic framework to characterize the material and energy resources used in manufacturing processes. The analysis and data span a wide range of processes from "conventional" processes such as machining, casting, and injection molding, to the so-called "advanced machining" processes such as electrical discharge machining and abrasive waterjet machining, and to the vapor-phase processes used in semiconductor and nanomaterials fabrication. In all, 20 processes are analyzed. The results show that the intensity of materials and energy used per unit of mass of material processed (measured either as specific energy or exergy) has increased by at least 6 orders of magnitude over the past several decades. The increase of material/energy intensity use has been primarily a consequence of the introduction of new manufacturing processes, rather than changes in traditional technologies. This phenomenon has been driven by the desire for precise small-scale devices and product features and enabled by stable and declining material and energy prices over this period. We illustrate the relevance of thermodynamics (including exergy analysis) for all processes in spite of the fact that long-lasting focus in manufacturing has been on product quality--not necessarily energy/material conversion efficiency. We promote the use of thermodynamics tools for analysis of manufacturing processes within the context of rapidly increasing relevance of sustainable human enterprises. We confirm that exergy analysis can be used to identify where resources are lost in these processes, which is the first step in proposing and/or redesigning new more efficient processes.

19 CFR 10.814 - Direct costs of processing operations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... manufacture of the specific good, including fringe benefits, on-the-job training, and the costs of engineering..., design, engineering, and blueprint costs, to the extent that they are allocable to the specific good; (4... 19 Customs Duties 1 2014-04-01 2014-04-01 false Direct costs of processing operations. 10.814...

19 CFR 10.774 - Direct costs of processing operations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... manufacture of the specific good, including fringe benefits, on-the-job training, and the costs of engineering..., design, engineering, and blueprint costs, to the extent that they are allocable to the specific good; (4... 19 Customs Duties 1 2014-04-01 2014-04-01 false Direct costs of processing operations. 10.774...

16 CFR 1615.31 - Labeling, recordkeeping, advertising, retail display and guaranties.

Code of Federal Regulations, 2010 CFR

2010-01-01

... records required must establish a line of continuity through the process of manufacture of each production... manufacturing specifications relating the same to prototype and production testing and to the production units... such sale or delivery shall be identified by production unit or by style. A style is a garment design...

Data management for Computer-Aided Engineering (CAE)

NASA Technical Reports Server (NTRS)

Bryant, W. A.; Smith, M. R.

1984-01-01

Analysis of data flow through the design and manufacturing processes has established specific information management requirements and identified unique problems. The application of data management technology to the engineering/manufacturing environment addresses these problems. An overview of the IPAD prototype data base management system, representing a partial solution to these problems, is presented here.

10 CFR 32.26 - Gas and aerosol detectors containing byproduct material: Requirements for license to manufacture...

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Gas and aerosol detectors containing byproduct material... CONTAINING BYPRODUCT MATERIAL Exempt Concentrations and Items § 32.26 Gas and aerosol detectors containing... application for a specific license to manufacture, process, or produce gas and aerosol detectors containing...

10 CFR 32.26 - Gas and aerosol detectors containing byproduct material: Requirements for license to manufacture...

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Gas and aerosol detectors containing byproduct material... CONTAINING BYPRODUCT MATERIAL Exempt Concentrations and Items § 32.26 Gas and aerosol detectors containing... application for a specific license to manufacture, process, or produce gas and aerosol detectors containing...

40 CFR 720.45 - Information that must be included in the notice form.

Code of Federal Regulations, 2013 CFR

2013-07-01

... relating to the manufacture, processing, distribution in commerce, use, and disposal of the new chemical substance: (a)(1) The specific chemical identity of the substance that the person intends to manufacture or import, which includes the following: (i) The currently correct Chemical Abstracts (CA) name for the...

40 CFR 720.45 - Information that must be included in the notice form.

Code of Federal Regulations, 2014 CFR

2014-07-01

... relating to the manufacture, processing, distribution in commerce, use, and disposal of the new chemical substance: (a)(1) The specific chemical identity of the substance that the person intends to manufacture or import, which includes the following: (i) The currently correct Chemical Abstracts (CA) name for the...

40 CFR 720.45 - Information that must be included in the notice form.

Code of Federal Regulations, 2012 CFR

2012-07-01

... relating to the manufacture, processing, distribution in commerce, use, and disposal of the new chemical substance: (a)(1) The specific chemical identity of the substance that the person intends to manufacture or import, which includes the following: (i) The currently correct Chemical Abstracts (CA) name for the...

40 CFR 720.45 - Information that must be included in the notice form.

Code of Federal Regulations, 2011 CFR

2011-07-01

... relating to the manufacture, processing, distribution in commerce, use, and disposal of the new chemical substance: (a)(1) The specific chemical identity of the substance that the person intends to manufacture or import, which includes the following: (i) The currently correct Chemical Abstracts (CA) name for the...

Comparative study of manufacturing condyle implant using rapid prototyping and CNC machining

NASA Astrophysics Data System (ADS)

Bojanampati, S.; Karthikeyan, R.; Islam, MD; Venugopal, S.

2018-04-01

Injuries to the cranio-maxillofacial area caused by road traffic accidents (RTAs), fall from heights, birth defects, metabolic disorders and tumors affect a rising number of patients in the United Arab Emirates (UAE), and require maxillofacial surgery. Mandibular reconstruction poses a specific challenge in both functionality and aesthetics, and involves replacement of the damaged bone by a custom made implant. Due to material, design cycle time and manufacturing process time, such implants are in many instances not affordable to patients. In this paper, the feasibility of designing and manufacturing low-cost, custom made condyle implant is assessed using two different approaches, consisting of rapid prototyping and three-axis computer numerically controlled (CNC) machining. Two candidate rapid prototyping techniques are considered, namely fused deposition modeling (FDM) and three-dimensional printing followed by sand casting The feasibility of the proposed manufacturing processes is evaluated based on manufacturing time, cost, quality, and reliability.

A mask quality control tool for the OSIRIS multi-object spectrograph

NASA Astrophysics Data System (ADS)

López-Ruiz, J. C.; Vaz Cedillo, Jacinto Javier; Ederoclite, Alessandro; Bongiovanni, Ángel; González Escalera, Víctor

2012-09-01

OSIRIS multi object spectrograph uses a set of user-customised-masks, which are manufactured on-demand. The manufacturing process consists of drilling the specified slits on the mask with the required accuracy. Ensuring that slits are on the right place when observing is of vital importance. We present a tool for checking the quality of the process of manufacturing the masks which is based on analyzing the instrument images obtained with the manufactured masks on place. The tool extracts the slit information from these images, relates specifications with the extracted slit information, and finally communicates to the operator if the manufactured mask fulfills the expectations of the mask designer. The proposed tool has been built using scripting languages and using standard libraries such as opencv, pyraf and scipy. The software architecture, advantages and limits of this tool in the lifecycle of a multiobject acquisition are presented.

At-line validation of a process analytical technology approach for quality control of melamine-urea-formaldehyde resin in composite wood-panel production using near infrared spectroscopy.

PubMed

Meder, Roger; Stahl, Wolfgang; Warburton, Paul; Woolley, Sam; Earnshaw, Scott; Haselhofer, Klaus; van Langenberg, Ken; Ebdon, Nick; Mulder, Roger

2017-01-01

The reactivity of melamine-urea-formaldehyde resins is of key importance in the manufacture of engineered wood products such as medium density fibreboard (MDF) and other wood composite products. Often the MDF manufacturing plant has little available information on the resin reactivity other than details of the resin specification at the time of batch manufacture, which often occurs off-site at a third-party resin plant. Often too, fresh resin on delivery at the MDF plant is mixed with variable volume of aged resin in storage tanks, thereby rendering any specification of the fresh resin batch obsolete. It is therefore highly desirable to develop a real-time, at-line or on-line, process analytical technology to monitor the quality of the resin prior to MDF panel manufacture. Near infrared (NIR) spectroscopy has been calibrated against standard quality methods and against 13 C nuclear magnetic resonance (NMR) measures of molecular composition in order to provide at-line process analytical technology (PAT), to monitor the resin quality, particularly the formaldehyde content of the resin. At-line determination of formaldehyde content in the resin was made possible using a six-factor calibration with an R 2 (cal) value of 0.973, and R 2 (CV) value of 0.929 and a root-mean-square error of cross-validation of 0.01. This calibration was then used to generate control charts of formaldehyde content at regular four-hourly periods during MDF panel manufacture in a commercial MDF manufacturing plant.

Low cost composite manufacturing utilizing intelligent pultrusion and resin transfer molding (IPRTM)

NASA Astrophysics Data System (ADS)

Bradley, James E.; Wysocki, Tadeusz S., Jr.

1993-02-01

This article describes an innovative method for the economical manufacturing of large, intricately-shaped tubular composite parts. Proprietary intelligent process control techniques are combined with standard pultrusion and RTM methodologies to provide high part throughput, performance, and quality while substantially reducing scrap, rework costs, and labor requirements. On-line process monitoring and control is achieved through a smart tooling interface consisting of modular zone tiles installed on part-specific die assemblies. Real-time archiving of process run parameters provides enhanced SPC and SQC capabilities.

Validation of the manufacturing process used to produce long-acting recombinant factor IX Fc fusion protein.

PubMed

McCue, J; Osborne, D; Dumont, J; Peters, R; Mei, B; Pierce, G F; Kobayashi, K; Euwart, D

2014-07-01

Recombinant factor IX Fc (rFIXFc) fusion protein is the first of a new class of bioengineered long-acting factors approved for the treatment and prevention of bleeding episodes in haemophilia B. The aim of this work was to describe the manufacturing process for rFIXFc, to assess product quality and to evaluate the capacity of the process to remove impurities and viruses. This manufacturing process utilized a transferable and scalable platform approach established for therapeutic antibody manufacturing and adapted for production of the rFIXFc molecule. rFIXFc was produced using a process free of human- and animal-derived raw materials and a host cell line derived from human embryonic kidney (HEK) 293H cells. The process employed multi-step purification and viral clearance processing, including use of a protein A affinity capture chromatography step, which binds to the Fc portion of the rFIXFc molecule with high affinity and specificity, and a 15 nm pore size virus removal nanofilter. Process validation studies were performed to evaluate identity, purity, activity and safety. The manufacturing process produced rFIXFc with consistent product quality and high purity. Impurity clearance validation studies demonstrated robust and reproducible removal of process-related impurities and adventitious viruses. The rFIXFc manufacturing process produces a highly pure product, free of non-human glycan structures. Validation studies demonstrate that this product is produced with consistent quality and purity. In addition, the scalability and transferability of this process are key attributes to ensure consistent and continuous supply of rFIXFc. © 2014 The Authors. Haemophilia Published by John Wiley & Sons Ltd.

Manufacturing Methods and Technology (MM&T) program. 10.6 micrometer carbon dioxide TEA (Transverely Excited Atmospheric) lasers

NASA Astrophysics Data System (ADS)

Luck, C. F.

1983-06-01

This report documents the efforts of Raytheon Company to conduct a manufacturing methods and technology (MM&T) program for 10.6 micrometer carbon dioxide TEA lasers. A set of laser parameters is given and a conforming tube design is described. Results of thermal and mechanical stress analyses are detailed along with a procedure for assembling and testing the laser tube. Also provided are purchase specifications for optics and process specifications for some of the essential operations.

Understanding Mechanical Design with Respect to Manufacturability

NASA Technical Reports Server (NTRS)

Mondell, Skyler

2010-01-01

At the NASA Prototype Development Laboratory in Kennedy Space Center, Fl, several projects concerning different areas of mechanical design were undertaken in order to better understand the relationship between mechanical design and manufacturabiIity. The assigned projects pertained specifically to the NASA Space Shuttle, Constellation, and Expendable Launch Vehicle programs. During the work term, mechanical design practices relating to manufacturing processes were learned and utilized in order to obtain an understanding of mechanical design with respect to manufacturability.

Achieving continuous manufacturing: technologies and approaches for synthesis, workup, and isolation of drug substance. May 20-21, 2014 Continuous Manufacturing Symposium.

PubMed

Baxendale, Ian R; Braatz, Richard D; Hodnett, Benjamin K; Jensen, Klavs F; Johnson, Martin D; Sharratt, Paul; Sherlock, Jon-Paul; Florence, Alastair J

2015-03-01

This whitepaper highlights current challenges and opportunities associated with continuous synthesis, workup, and crystallization of active pharmaceutical ingredients (drug substances). We describe the technologies and requirements at each stage and emphasize the different considerations for developing continuous processes compared with batch. In addition to the specific sequence of operations required to deliver the necessary chemical and physical transformations for continuous drug substance manufacture, consideration is also given to how adoption of continuous technologies may impact different manufacturing stages in development from discovery, process development, through scale-up and into full scale production. The impact of continuous manufacture on drug substance quality and the associated challenges for control and for process safety are also emphasized. In addition to the technology and operational considerations necessary for the adoption of continuous manufacturing (CM), this whitepaper also addresses the cultural, as well as skills and training, challenges that will need to be met by support from organizations in order to accommodate the new work flows. Specific action items for industry leaders are: Develop flow chemistry toolboxes, exploiting the advantages of flow processing and including highly selective chemistries that allow use of simple and effective continuous workup technologies. Availability of modular or plug and play type equipment especially for workup to assist in straightforward deployment in the laboratory. As with learning from other industries, standardization is highly desirable and will require cooperation across industry and academia to develop and implement. Implement and exploit process analytical technologies (PAT) for real-time dynamic control of continuous processes. Develop modeling and simulation techniques to support continuous process development and control. Progress is required in multiphase systems such as crystallization. Involve all parts of the organization from discovery, research and development, and manufacturing in the implementation of CM. Engage with academia to develop the training provision to support the skills base for CM, particularly in flow chemistry, physical chemistry, and chemical engineering skills at the chemistry-process interface. Promote and encourage publication and dissemination of examples of CM across the sector to demonstrate capability, engage with regulatory comment, and establish benchmarks for performance and highlight challenges. Develop the economic case for CM of drug substance. This will involve various stakeholders at project and business level, however establishing the critical economic drivers is critical to driving the transformation in manufacturing. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Materials processing in zero gravity. [space manufacturing

NASA Technical Reports Server (NTRS)

Wuenscher, H. F.

1973-01-01

Manufacturing processes which are expected to show drastic changes in a space environment due to the absence of earth gravity are classified according to (1) buoyancy and thermal convection sensitive processes and (2) processes where molecular forces like cohesion and adhesion remain as the relatively strongest and hence controlling factors. Some specific process demonstration experiments carried out during the Apollo 14 mission and in the Skylab program are described. These include chemical separation by electrophoresis, the M551 metals melting experiment, the M552 exothermic brazing experiment, the M553 sphere forming experiment, the M554 composite casting experiment, and the M555 gallium arsenide crystal growth experiment.

Contamination-Free Manufacturing: Tool Component Qualification, Verification and Correlation with Wafers

NASA Astrophysics Data System (ADS)

Tan, Samantha H.; Chen, Ning; Liu, Shi; Wang, Kefei

2003-09-01

As part of the semiconductor industry "contamination-free manufacturing" effort, significant emphasis has been placed on reducing potential sources of contamination from process equipment and process equipment components. Process tools contain process chambers and components that are exposed to the process environment or process chemistry and in some cases are in direct contact with production wafers. Any contamination from these sources must be controlled or eliminated in order to maintain high process yields, device performance, and device reliability. This paper discusses new nondestructive analytical methods for quantitative measurement of the cleanliness of metal, quartz, polysilicon and ceramic components that are used in process equipment tools. The goal of these new procedures is to measure the effectiveness of cleaning procedures and to verify whether a tool component part is sufficiently clean for installation and subsequent routine use in the manufacturing line. These procedures provide a reliable "qualification method" for tool component certification and also provide a routine quality control method for reliable operation of cleaning facilities. Cost advantages to wafer manufacturing include higher yields due to improved process cleanliness and elimination of yield loss and downtime resulting from the installation of "bad" components in process tools. We also discuss a representative example of wafer contamination having been linked to a specific process tool component.

75 FR 26321 - Public Meeting on Future Policy and Rulemaking for Normal, Utility, Acrobatic, and Commuter...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-11

..., and rulemaking. Specifically, we would like feedback from manufacturers, pilots, owners, mechanics... Airplane Certification Process Study,'' addressed the following areas: Structure and Process of Part 23...

Cold Spraying of Armstrong Process Titanium Powder for Additive Manufacturing

NASA Astrophysics Data System (ADS)

MacDonald, D.; Fernández, R.; Delloro, F.; Jodoin, B.

2017-04-01

Titanium parts are ideally suited for aerospace applications due to their unique combination of high specific strength and excellent corrosion resistance. However, titanium as bulk material is expensive and challenging/costly to machine. Production of complex titanium parts through additive manufacturing looks promising, but there are still many barriers to overcome before reaching mainstream commercialization. The cold gas dynamic spraying process offers the potential for additive manufacturing of large titanium parts due to its reduced reactive environment, its simplicity to operate, and the high deposition rates it offers. A few challenges are to be addressed before the additive manufacturing potential of titanium by cold gas dynamic spraying can be reached. In particular, it is known that titanium is easy to deposit by cold gas dynamic spraying, but the deposits produced are usually porous when nitrogen is used as the carrier gas. In this work, a method to manufacture low-porosity titanium components at high deposition efficiencies is revealed. The components are produced by combining low-pressure cold spray using nitrogen as the carrier gas with low-cost titanium powder produced using the Armstrong process. The microstructure and mechanical properties of additive manufactured titanium components are investigated.

Automation of cellular therapy product manufacturing: results of a split validation comparing CD34 selection of peripheral blood stem cell apheresis product with a semi-manual vs. an automatic procedure.

PubMed

Hümmer, Christiane; Poppe, Carolin; Bunos, Milica; Stock, Belinda; Wingenfeld, Eva; Huppert, Volker; Stuth, Juliane; Reck, Kristina; Essl, Mike; Seifried, Erhard; Bonig, Halvard

2016-03-16

Automation of cell therapy manufacturing promises higher productivity of cell factories, more economical use of highly-trained (and costly) manufacturing staff, facilitation of processes requiring manufacturing steps at inconvenient hours, improved consistency of processing steps and other benefits. One of the most broadly disseminated engineered cell therapy products is immunomagnetically selected CD34+ hematopoietic "stem" cells (HSCs). As the clinical GMP-compliant automat CliniMACS Prodigy is being programmed to perform ever more complex sequential manufacturing steps, we developed a CD34+ selection module for comparison with the standard semi-automatic CD34 "normal scale" selection process on CliniMACS Plus, applicable for 600 × 10(6) target cells out of 60 × 10(9) total cells. Three split-validation processings with healthy donor G-CSF-mobilized apheresis products were performed; feasibility, time consumption and product quality were assessed. All processes proceeded uneventfully. Prodigy runs took about 1 h longer than CliniMACS Plus runs, albeit with markedly less hands-on operator time and therefore also suitable for less experienced operators. Recovery of target cells was the same for both technologies. Although impurities, specifically T- and B-cells, were 5 ± 1.6-fold and 4 ± 0.4-fold higher in the Prodigy products (p = ns and p = 0.013 for T and B cell depletion, respectively), T cell contents per kg of a virtual recipient receiving 4 × 10(6) CD34+ cells/kg was below 10 × 10(3)/kg even in the worst Prodigy product and thus more than fivefold below the specification of CD34+ selected mismatched-donor stem cell products. The products' theoretical clinical usability is thus confirmed. This split validation exercise of a relatively short and simple process exemplifies the potential of automatic cell manufacturing. Automation will further gain in attractiveness when applied to more complex processes, requiring frequent interventions or handling at unfavourable working hours, such as re-targeting of T-cells.

A framework for the computer-aided planning and optimisation of manufacturing processes for components with functional graded properties

NASA Astrophysics Data System (ADS)

Biermann, D.; Gausemeier, J.; Heim, H.-P.; Hess, S.; Petersen, M.; Ries, A.; Wagner, T.

2014-05-01

In this contribution a framework for the computer-aided planning and optimisation of functional graded components is presented. The framework is divided into three modules - the "Component Description", the "Expert System" for the synthetisation of several process chains and the "Modelling and Process Chain Optimisation". The Component Description module enhances a standard computer-aided design (CAD) model by a voxel-based representation of the graded properties. The Expert System synthesises process steps stored in the knowledge base to generate several alternative process chains. Each process chain is capable of producing components according to the enhanced CAD model and usually consists of a sequence of heating-, cooling-, and forming processes. The dependencies between the component and the applied manufacturing processes as well as between the processes themselves need to be considered. The Expert System utilises an ontology for that purpose. The ontology represents all dependencies in a structured way and connects the information of the knowledge base via relations. The third module performs the evaluation of the generated process chains. To accomplish this, the parameters of each process are optimised with respect to the component specification, whereby the result of the best parameterisation is used as representative value. Finally, the process chain which is capable of manufacturing a functionally graded component in an optimal way regarding to the property distributions of the component description is presented by means of a dedicated specification technique.

Planning for the semiconductor manufacturer of the future

NASA Technical Reports Server (NTRS)

Fargher, Hugh E.; Smith, Richard A.

1992-01-01

Texas Instruments (TI) is currently contracted by the Air Force Wright Laboratory and the Defense Advanced Research Projects Agency (DARPA) to develop the next generation flexible semiconductor wafer fabrication system called Microelectronics Manufacturing Science & Technology (MMST). Several revolutionary concepts are being pioneered on MMST, including the following: new single-wafer rapid thermal processes, in-situ sensors, cluster equipment, and advanced Computer Integrated Manufacturing (CIM) software. The objective of the project is to develop a manufacturing system capable of achieving an order of magnitude improvement in almost all aspects of wafer fabrication. TI was awarded the contract in Oct., 1988, and will complete development with a fabrication facility demonstration in April, 1993. An important part of MMST is development of the CIM environment responsible for coordinating all parts of the system. The CIM architecture being developed is based on a distributed object oriented framework made of several cooperating subsystems. The software subsystems include the following: process control for dynamic control of factory processes; modular processing system for controlling the processing equipment; generic equipment model which provides an interface between processing equipment and the rest of the factory; specification system which maintains factory documents and product specifications; simulator for modelling the factory for analysis purposes; scheduler for scheduling work on the factory floor; and the planner for planning and monitoring of orders within the factory. This paper first outlines the division of responsibility between the planner, scheduler, and simulator subsystems. It then describes the approach to incremental planning and the way in which uncertainty is modelled within the plan representation. Finally, current status and initial results are described.

75 FR 364 - Notice of a Project Waiver of Section 1605 (Buy American Requirement) of the American Recovery...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-05

... City, ND for the Zenon ZeeWeed 1000 membrane filter manufactured by General Electric Water & Process... membrane filters are manufactured in Canada, and meet Valley City's performance specifications and... the purchase of the Zenon ZeeWeed 1000 membrane filter for the Surface Water Treatment Plant upgrades...

Bulk silica transmission grating made by reactive ion etching for NIR space instruments

NASA Astrophysics Data System (ADS)

Caillat, Amandine; Pascal, Sandrine; Tisserand, Stéphane; Dohlen, Kjetil; Grange, Robert; Sauget, Vincent; Gautier, Sophie

2014-07-01

A GRISM, made of a grating on a prism, allow combining image and spectroscopy of the same field of view with the same optical system and detector, thus simplify instrument concept. New GRISM designs impose technical specifications difficult to reach with classical grating manufacturing processes: large useful aperture (>100mm), low groove frequency (<30g/mm), small blaze angle (<3°) and, last but not least, line curvature allowing wavefront corrections. In addition, gratings are commonly made of resin which may not be suitable to withstand the extreme space environment. Therefore, in the frame of a R&D project financed by the CNES, SILIOS Technologies developed a new resin-free grating manufacturing process and realized a first 80mm diameter prototype optically tested at LAM. We present detailed specifications of this resin-free grating, the manufacturing process, optical setups and models for optical performance verification and very encouraging results obtained on the first 80mm diameter grating prototype: >80% transmitted efficiency, <30nm RMS wavefront error, groove shape and roughness very close to theory and uniform over the useful aperture.

Thermally stable booster explosive and process for manufacture

DOEpatents

Quinlin, William T [Amarillo, TX; Thorpe, Raymond [Amarillo, TX; Lightfoot, James M [Amarillo, TX

2006-03-21

A thermally stable booster explosive and process for the manufacture of the explosive. The product explosive is 2,4,7,9-tetranitro-10H-benzo[4,5]furo[3,2-b]indole (TNBFI). A reactant/solvent such as n-methylpyrrolidone (NMP) or dimethyl formamide (DMF) is made slightly basic. The solution is heated to reduce the water content. The solution is cooled and hexanitrostilbene is added. The solution is heated to a predetermined temperature for a specific time period, cooled, and the product is collected by filtration.

The Role of Evolutive Elastic Properties in the Performance of a Sheet Formed Spring Applied in Multimedia Car Industry

NASA Astrophysics Data System (ADS)

Faria, J.; Silva, J.; Bernardo, P.; Araújo, M.; Alves, J. L.

2016-08-01

The manufacturing process and the behaviour of a spring manufactured from an aluminium sheet is described and investigated in this work considering the specifications for the in-service conditions. The spring is intended to be applied in car multimedia industry to replace bolted connections. Among others, are investigated the roles of the constitutive parameters and the hypothesis of evolutive elastic properties with the plastic work in the multistep forming process and in working conditions.

SUBSTITUTION OF CADMIUM CYANIDE ELECTROPLATING WITH ZINC CHLORIDE ELECTROPLATING

EPA Science Inventory

The study evaluated the zinc chloride electroplating process as a substitute for cadmium cyanide electroplating in the manufacture of industrial connectors and fittings at Aeroquip Corporation. The process substitution eliminates certain wastes, specifically cadmium and cyanide, ...

Manufacture of tumor- and virus-specific T lymphocytes for adoptive cell therapies

PubMed Central

Wang, X; Rivière, I

2015-01-01

Adoptive transfer of tumor-infiltrating lymphocytes (TILs) and genetically engineered T lymphocytes expressing chimeric antigen receptors (CARs) or conventional alpha/beta T-cell receptors (TCRs), collectively termed adoptive cell therapy (ACT), is an emerging novel strategy to treat cancer patients. Application of ACT has been constrained by the ability to isolate and expand functional tumor-reactive T cells. The transition of ACT from a promising experimental regimen to an established standard of care treatment relies largely on the establishment of safe, efficient, robust and cost-effective cell manufacturing protocols. The manufacture of cellular products under current good manufacturing practices (cGMPs) has a critical role in the process. Herein, we review current manufacturing methods for the large-scale production of clinical-grade TILs, virus-specific and genetically modified CAR or TCR transduced T cells in the context of phase I/II clinical trials as well as the regulatory pathway to get these complex personalized cellular products to the clinic. PMID:25721207

Manufacture of tumor- and virus-specific T lymphocytes for adoptive cell therapies.

PubMed

Wang, X; Rivière, I

2015-03-01

Adoptive transfer of tumor-infiltrating lymphocytes (TILs) and genetically engineered T lymphocytes expressing chimeric antigen receptors (CARs) or conventional alpha/beta T-cell receptors (TCRs), collectively termed adoptive cell therapy (ACT), is an emerging novel strategy to treat cancer patients. Application of ACT has been constrained by the ability to isolate and expand functional tumor-reactive T cells. The transition of ACT from a promising experimental regimen to an established standard of care treatment relies largely on the establishment of safe, efficient, robust and cost-effective cell manufacturing protocols. The manufacture of cellular products under current good manufacturing practices (cGMPs) has a critical role in the process. Herein, we review current manufacturing methods for the large-scale production of clinical-grade TILs, virus-specific and genetically modified CAR or TCR transduced T cells in the context of phase I/II clinical trials as well as the regulatory pathway to get these complex personalized cellular products to the clinic.

Current good manufacturing practice in manufacturing, processing, packing, or holding of drugs; revision of certain labeling controls--FDA. Final rule.

PubMed

1993-08-03

The Food and Drug Administration (FDA) is amending the current good manufacturing practice (CGMP) regulations for human and veterinary drug products to revise certain labeling control provisions. Specifically, the final rule defines the term "gang-printed labeling," specifies conditions for the use of gang-printed or cut labeling, exempts manufacturers that employ automated 100-percent labeling inspection systems from CGMP labeling reconciliation requirements, and requires manufacturers to identify filled drug product containers that are set aside and held in an unlabeled condition for future labeling operations. These changes are intended to reduce the frequency of drug product mislabeling and associated drug product recalls.

Role of RIS/APC for manufacturing RFG/LSD. [Refinery Information Systems/Advanced Process Control, ReFormulated Gasoline/Low Sulfur Diesels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Latour, P.R.

Revolutionary changes in quality specifications (number, complexity, uncertainty, economic sensitivity) for reformulated gasolines (RFG) and low-sulfur diesels (LSD) are being addressed by powerful, new, computer-integrated manufacturing technology for Refinery Information Systems and Advanced Process Control (RIS/APC). This paper shows how the five active RIS/APC functions: performance measurement, optimization, scheduling, control and integration are used to manufacture new, clean fuels competitively. With current industry spending for this field averaging 2 to 3 cents/bbl crude, many refineries can capture 50 to 100 cents/bbl if the technology is properly employed and sustained throughout refining operations, organizations, and businesses.

A practical discussion of risk management for manufacturing of pharmaceutical products.

PubMed

Mollah, A Hamid; Baseman, Harold S; Long, Mike; Rathore, Anurag S

2014-01-01

Quality risk management (QRM) is now a regulatory expectation, and it makes good business sense. The goal of the risk assessment is to increase process understanding and deliver safe and effective product to the patients. Risk analysis and management is an acceptable and effective way to minimize patient risk and determine the appropriate level of controls in manufacturing. While understanding the elements of QRM is important, knowing how to apply them in the manufacturing environment is essential for effective process performance and control. This article will preview application of QRM in pharmaceutical and biopharmaceutical manufacturing to illustrate how QRM can help the reader achieve that objective. There are several areas of risk that a drug company may encounter in pharmaceutical manufacturing, specifically addressing oral solid and liquid formulations. QRM tools can be used effectively to identify the risks and develop strategy to minimize or control them. Risks are associated throughout the biopharmaceutical manufacturing process-from raw material supply through manufacturing and filling operations to final distribution via a controlled cold chain process. Assessing relevant attributes and risks for biotechnology-derived products is more complicated and challenging for complex pharmaceuticals. This paper discusses key risk factors in biopharmaceutical manufacturing. Successful development and commercialization of pharmaceutical products is all about managing risks. If a company was to take zero risk, most likely the path to commercialization would not be commercially viable. On the other hand, if the risk taken was too much, the product is likely to have a suboptimal safety and efficacy profile and thus is unlikely to be a successful product. This article addresses the topic of quality risk management with the key objective of minimizing patient risk while creating an optimal process and product. Various tools are presented to aid implementation of these concepts. © PDA, Inc. 2014.

AMPS/PC - AUTOMATIC MANUFACTURING PROGRAMMING SYSTEM

NASA Technical Reports Server (NTRS)

Schroer, B. J.

1994-01-01

The AMPS/PC system is a simulation tool designed to aid the user in defining the specifications of a manufacturing environment and then automatically writing code for the target simulation language, GPSS/PC. The domain of problems that AMPS/PC can simulate are manufacturing assembly lines with subassembly lines and manufacturing cells. The user defines the problem domain by responding to the questions from the interface program. Based on the responses, the interface program creates an internal problem specification file. This file includes the manufacturing process network flow and the attributes for all stations, cells, and stock points. AMPS then uses the problem specification file as input for the automatic code generator program to produce a simulation program in the target language GPSS. The output of the generator program is the source code of the corresponding GPSS/PC simulation program. The system runs entirely on an IBM PC running PC DOS Version 2.0 or higher and is written in Turbo Pascal Version 4 requiring 640K memory and one 360K disk drive. To execute the GPSS program, the PC must have resident the GPSS/PC System Version 2.0 from Minuteman Software. The AMPS/PC program was developed in 1988.

Enhanced clinical-scale manufacturing of TCR transduced T-cells using closed culture system modules.

PubMed

Jin, Jianjian; Gkitsas, Nikolaos; Fellowes, Vicki S; Ren, Jiaqiang; Feldman, Steven A; Hinrichs, Christian S; Stroncek, David F; Highfill, Steven L

2018-01-24

Genetic engineering of T-cells to express specific T cell receptors (TCR) has emerged as a novel strategy to treat various malignancies. More widespread utilization of these types of therapies has been somewhat constrained by the lack of closed culture processes capable of expanding sufficient numbers of T-cells for clinical application. Here, we evaluate a process for robust clinical grade manufacturing of TCR gene engineered T-cells. TCRs that target human papillomavirus E6 and E7 were independently tested. A 21 day process was divided into a transduction phase (7 days) and a rapid expansion phase (14 days). This process was evaluated using two healthy donor samples and four samples obtained from patients with epithelial cancers. The process resulted in ~ 2000-fold increase in viable nucleated cells and high transduction efficiencies (64-92%). At the end of culture, functional assays demonstrated that these cells were potent and specific in their ability to kill tumor cells bearing target and secrete large quantities of interferon and tumor necrosis factor. Both phases of culture were contained within closed or semi-closed modules, which include automated density gradient separation and cell culture bags for the first phase and closed GREX culture devices and wash/concentrate systems for the second phase. Large-scale manufacturing using modular systems and semi-automated devices resulted in highly functional clinical-grade TCR transduced T-cells. This process is now in use in actively accruing clinical trials and the NIH Clinical Center and can be utilized at other cell therapy manufacturing sites that wish to scale-up and optimize their processing using closed systems.

Additive Manufacturing of Low Cost Upper Stage Propulsion Components

NASA Technical Reports Server (NTRS)

Protz, Christopher; Bowman, Randy; Cooper, Ken; Fikes, John; Taminger, Karen; Wright, Belinda

2014-01-01

NASA is currently developing Additive Manufacturing (AM) technologies and design tools aimed at reducing the costs and manufacturing time of regeneratively cooled rocket engine components. These Low Cost Upper Stage Propulsion (LCUSP) tasks are funded through NASA's Game Changing Development Program in the Space Technology Mission Directorate. The LCUSP project will develop a copper alloy additive manufacturing design process and develop and optimize the Electron Beam Freeform Fabrication (EBF3) manufacturing process to direct deposit a nickel alloy structural jacket and manifolds onto an SLM manufactured GRCop chamber and Ni-alloy nozzle. In order to develop these processes, the project will characterize both the microstructural and mechanical properties of the SLMproduced GRCop-84, and will explore and document novel design techniques specific to AM combustion devices components. These manufacturing technologies will be used to build a 25K-class regenerative chamber and nozzle (to be used with tested DMLS injectors) that will be tested individually and as a system in hot fire tests to demonstrate the applicability of the technologies. These tasks are expected to bring costs and manufacturing time down as spacecraft propulsion systems typically comprise more than 70% of the total vehicle cost and account for a significant portion of the development schedule. Additionally, high pressure/high temperature combustion chambers and nozzles must be regeneratively cooled to survive their operating environment, causing their design to be time consuming and costly to build. LCUSP presents an opportunity to develop and demonstrate a process that can infuse these technologies into industry, build competition, and drive down costs of future engines.

40 CFR 761.372 - Specific requirements for relatively clean surfaces.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Specific requirements for relatively clean surfaces. 761.372 Section 761.372 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT POLYCHLORINATED BIPHENYLS (PCBs) MANUFACTURING, PROCESSING...

Computer integrated manufacturing/processing in the HPI. [Hydrocarbon Processing Industry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoshimura, J.S.

1993-05-01

Hydrocarbon Processing and Systemhouse Inc., developed a comprehensive survey on the status of computer integrated manufacturing/processing (CIM/CIP) targeted specifically to the unique requirements of the hydrocarbon processing industry. These types of surveys and other benchmarking techniques can be invaluable in assisting companies to maximize business benefits from technology investments. The survey was organized into 5 major areas: CIM/CIP planning, management perspective, functional applications, integration and technology infrastructure and trends. The CIM/CIP planning area dealt with the use and type of planning methods to plan, justify implement information technology projects. The management perspective section addressed management priorities, expenditure levels and implementationmore » barriers. The functional application area covered virtually all functional areas of organization and focused on the specific solutions and benefits in each of the functional areas. The integration section addressed the needs and integration status of the organization's functional areas. Finally, the technology infrastructure and trends section dealt with specific technologies in use as well as trends over the next three years. In February 1993, summary areas from preliminary results were presented at the 2nd International Conference on Productivity and Quality in the Hydrocarbon Processing Industry.« less

Serum neuron-specific enolase, biogenic amino-acids and neurobehavioral function in lead-exposed workers from lead-acid battery manufacturing process.

PubMed

Ravibabu, K; Barman, T; Rajmohan, H R

2015-01-01

The interaction between serum neuron-specific enolase (NSE), biogenic amino-acids and neurobehavioral function with blood lead levels in workers exposed to lead form lead-acid battery manufacturing process was not studied. To evaluate serum NSE and biogenic amino-acids (dopamine and serotonin) levels, and neurobehavioral performance among workers exposed to lead from lead-acid storage battery plant, and its relation with blood lead levels (BLLs). In a cross-sectional study, we performed biochemical and neurobehavioral function tests on 146 workers exposed to lead from lead-acid battery manufacturing process. BLLs were assessed by an atomic absorption spectrophotometer. Serum NSE, dopamine and serotonin were measured by ELISA. Neurobehavioral functions were assessed by CDC-recommended tests---simple reaction time (SRT), symbol digit substitution test (SDST), and serial digit learning test (SDLT). There was a significant correlation (r 0.199, p<0.05) between SDST and BLL. SDLT and SRT had also a significant positive correlation (r 0.238, p<0.01). NSE had a negative correlation (r -0.194, p<0.05) with serotonin level. Multiple linear regression analysis revealed that both SRT and SDST had positive significant associations with BLL. SRT also had a positive significant association with age. Serum NSE cannot be used as a marker for BLL. The only domain of neurobehavioral function tests that is affected by increased BLL in workers of lead-acid battery manufacturing process is that of the "attention and perception" (SDST).

An update on coating/manufacturing techniques of microneedles.

PubMed

Tarbox, Tamara N; Watts, Alan B; Cui, Zhengrong; Williams, Robert O

2017-12-29

Recently, results have been published for the first successful phase I human clinical trial investigating the use of dissolving polymeric microneedles… Even so, further clinical development represents an important hurdle that remains in the translation of microneedle technology to approved products. Specifically, the potential for accumulation of polymer within the skin upon repeated application of dissolving and coated microneedles, combined with a lack of safety data in humans, predicates a need for further clinical investigation. Polymers are an important consideration for microneedle technology-from both manufacturing and drug delivery perspectives. The use of polymers enables a tunable delivery strategy, but the scalability of conventional manufacturing techniques could arguably benefit from further optimization. Micromolding has been suggested in the literature as a commercially viable means to mass production of both dissolving and swellable microneedles. However, the reliance on master molds, which are commonly manufactured using resource intensive microelectronics industry-derived processes, imparts notable material and design limitations. Further, the inherently multi-step filling and handling processes associated with micromolding are typically batch processes, which can be challenging to scale up. Similarly, conventional microneedle coating processes often follow step-wise batch processing. Recent developments in microneedle coating and manufacturing techniques are highlighted, including micromilling, atomized spraying, inkjet printing, drawing lithography, droplet-born air blowing, electro-drawing, continuous liquid interface production, 3D printing, and polyelectrolyte multilayer coating. This review provides an analysis of papers reporting on potentially scalable production techniques for the coating and manufacturing of microneedles.

Lithium-Ion Batteries for Aerospace Applications

NASA Technical Reports Server (NTRS)

Surampudi, S.; Halpert, G.; Marsh, R. A.; James, R.

1999-01-01

This presentation reviews: (1) the goals and objectives, (2) the NASA and Airforce requirements, (3) the potential near term missions, (4) management approach, (5) the technical approach and (6) the program road map. The objectives of the program include: (1) develop high specific energy and long life lithium ion cells and smart batteries for aerospace and defense applications, (2) establish domestic production sources, and to demonstrate technological readiness for various missions. The management approach is to encourage the teaming of universities, R&D organizations, and battery manufacturing companies, to build on existing commercial and government technology, and to develop two sources for manufacturing cells and batteries. The technological approach includes: (1) develop advanced electrode materials and electrolytes to achieve improved low temperature performance and long cycle life, (2) optimize cell design to improve specific energy, cycle life and safety, (3) establish manufacturing processes to ensure predictable performance, (4) establish manufacturing processes to ensure predictable performance, (5) develop aerospace lithium ion cells in various AH sizes and voltages, (6) develop electronics for smart battery management, (7) develop a performance database required for various applications, and (8) demonstrate technology readiness for the various missions. Charts which review the requirements for the Li-ion battery development program are presented.

The process defines the product: what really matters in biosimilar design and production?

PubMed

Vulto, Arnold G; Jaquez, Orlando A

2017-08-01

Biologic drugs are highly complex molecules produced by living cells through a multistep manufacturing process. The key characteristics of these molecules, known as critical quality attributes (CQAs), can vary based on post-translational modifications that occur in the cellular environment or during the manufacturing process. The extent of the variation in each of the CQAs must be characterized for the originator molecule and systematically matched as closely as possible by the biosimilar developer to ensure bio-similarity. The close matching of the originator fingerprint is the foundation of the biosimilarity exercise, as the analytical tools designed to measure differences at the molecular level are far more sensitive and specific than tools available to physicians during clinical trials. Biosimilar development, therefore, has a greater focus on preclinical attributes compared with the development of an original biological agent. As changes in CQAs can occur at different stages of the manufacturing process, even small modifications to the process can alter biosimilar attributes beyond the point of similarity and impact clinical effectiveness and safety. The manufacturer's ability to provide consistent production and quality control will greatly influence the acceptance of biosimilars. To this end, preventing drift from the required specifications over time and avoiding the various implications brought by product shortage will enhance biosimilar integration into daily practice. As most prescribers are not familiar with this new drug development paradigm, educational programmes will be needed so that prescribers see biosimilars as fully equivalent, efficacious and safe medicines when compared with originator products. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

A Framework for Preliminary Design of Aircraft Structures Based on Process Information. Part 1

NASA Technical Reports Server (NTRS)

Rais-Rohani, Masoud

1998-01-01

This report discusses the general framework and development of a computational tool for preliminary design of aircraft structures based on process information. The described methodology is suitable for multidisciplinary design optimization (MDO) activities associated with integrated product and process development (IPPD). The framework consists of three parts: (1) product and process definitions; (2) engineering synthesis, and (3) optimization. The product and process definitions are part of input information provided by the design team. The backbone of the system is its ability to analyze a given structural design for performance as well as manufacturability and cost assessment. The system uses a database on material systems and manufacturing processes. Based on the identified set of design variables and an objective function, the system is capable of performing optimization subject to manufacturability, cost, and performance constraints. The accuracy of the manufacturability measures and cost models discussed here depend largely on the available data on specific methods of manufacture and assembly and associated labor requirements. As such, our focus in this research has been on the methodology itself and not so much on its accurate implementation in an industrial setting. A three-tier approach is presented for an IPPD-MDO based design of aircraft structures. The variable-complexity cost estimation methodology and an approach for integrating manufacturing cost assessment into design process are also discussed. This report is presented in two parts. In the first part, the design methodology is presented, and the computational design tool is described. In the second part, a prototype model of the preliminary design Tool for Aircraft Structures based on Process Information (TASPI) is described. Part two also contains an example problem that applies the methodology described here for evaluation of six different design concepts for a wing spar.

3D Printing Multi-Functionality: Embedded RF Antennas and Components

NASA Technical Reports Server (NTRS)

Shemelya, C. M.; Zemba, M.; Liang, M.; Espalin, D.; Kief, C.; Xin, H.; Wicker, R. B.; MacDonald, E. W.

2015-01-01

Significant research and press has recently focused on the fabrication freedom of Additive Manufacturing (AM) to create both conceptual models and final end-use products. This flexibility allows design modifications to be immediately reflected in 3D printed structures, creating new paradigms within the manufacturing process. 3D printed products will inevitably be fabricated locally, with unit-level customization, optimized to unique mission requirements. However, for the technology to be universally adopted, the processes must be enhanced to incorporate additional technologies; such as electronics, actuation, and electromagnetics. Recently, a novel 3D printing platform, Multi3D manufacturing, was funded by the presidential initiative for revitalizing manufacturing in the USA using 3D printing (America Makes - also known as the National Additive Manufacturing Innovation Institute). The Multi3D system specifically targets 3D printed electronics in arbitrary form; and building upon the potential of this system, this paper describes RF antennas and components fabricated through the integration of material extrusion 3D printing with embedded wire, mesh, and RF elements.

The specification of personalised insoles using additive manufacturing.

PubMed

Salles, André S; Gyi, Diane E

2012-01-01

Research has been conducted to explore a process that delivers insoles for personalised footwear for the high street using additive manufacturing (AM) and to evaluate the use of such insoles in terms of discomfort. Therefore, the footwear personalisation process was first identified: (1) foot capture; (2) anthropometric measurements; (3) insole design; and (4) additive manufacturing. In order to explore and evaluate this process, recreational runners were recruited. They had both feet scanned and 15 anthropometric measurements taken. Personalised insoles were designed from the scans and manufactured using AM. Participants were fitted with footwear under two experimental conditions: personalised and control, which were compared in terms of discomfort. The mean ratings for discomfort variables were generally low for both conditions and no significant differences were detected between conditions. In general, the personalisation process showed promise in terms of the scan data, although the foot capture position may not be considered 'gold standard'. Polyamide, the material used for the insoles, demonstrated positive attributes: visual inspection revealed no signs of breaking. The footwear personalisation process described and explored in this study shows potential and can be considered a good starting point for designer and researchers.

3D Printing of Polymer-Bonded Rare-Earth Magnets With a Variable Magnetic Compound Fraction for a Predefined Stray Field.

PubMed

Huber, Christian; Abert, Claas; Bruckner, Florian; Groenefeld, Martin; Schuschnigg, Stephan; Teliban, Iulian; Vogler, Christoph; Wautischer, Gregor; Windl, Roman; Suess, Dieter

2017-08-25

Additive manufacturing of polymer-bonded magnets is a recently developed technique, for single-unit production, and for structures that have been impossible to manufacture previously. Also, new possibilities to create a specific stray field around the magnet are triggered. The current work presents a method to 3D print polymer-bonded magnets with a variable magnetic compound fraction distribution. This means the saturation magnetization can be adjusted during the printing process to obtain a required external field of the manufactured magnets. A low-cost, end-user 3D printer with a mixing extruder is used to mix permanent magnetic filaments with pure polyamide (PA12) filaments. The magnetic filaments are compounded, extruded, and characterized for the printing process. To deduce the quality of the manufactured magnets with a variable magnetic compound fraction, an inverse stray field framework is developed. The effectiveness of the printing process and the simulation method is shown. It can also be used to manufacture magnets that produce a predefined stray field in a given region. This opens new possibilities for magnetic sensor applications. This setup and simulation framework allows the design and manufacturing of polymer-bonded permanent magnets, which are impossible to create with conventional methods.

14 CFR § 1240.102 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... experimental or beta phase of development, that performs in accordance with its specifications, and includes... mathematical, engineering or scientific concept, idea, design, process, or product. (h) Innovator means any..., method, process, machine, manufacture, design, or composition of matter, or any new and useful...

40 CFR 63.5400 - How do I measure the quantity of leather processed?

Code of Federal Regulations, 2011 CFR

2011-07-01

... leather processed? 63.5400 Section 63.5400 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... processed or shipped leather with a computer scanning system accurate to 0.1 square feet. The computer scanning system must be initially calibrated for minimum accuracy to the manufacturer's specifications. For...

40 CFR 63.5400 - How do I measure the quantity of leather processed?

Code of Federal Regulations, 2010 CFR

2010-07-01

... leather processed? 63.5400 Section 63.5400 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... processed or shipped leather with a computer scanning system accurate to 0.1 square feet. The computer scanning system must be initially calibrated for minimum accuracy to the manufacturer's specifications. For...

Introduction of novel 3D-printed superficial applicators for high-dose-rate skin brachytherapy.

PubMed

Jones, Emma-Louise; Tonino Baldion, Anna; Thomas, Christopher; Burrows, Tom; Byrne, Nick; Newton, Victoria; Aldridge, Sarah

Custom-made surface mold applicators often allow more flexibility when carrying out skin brachytherapy, particularly for small treatment areas with high surface obliquity. They can, however, be difficult to manufacture, particularly if there is a lack of experience in superficial high-dose-rate brachytherapy techniques or with limited resources. We present a novel method of manufacturing superficial brachytherapy applicators utilizing three-dimensional (3D)-printing techniques. We describe the treatment planning process and the process of applicator manufacture. The treatment planning process, with the introduction of a pre-plan, allows for an "ideal" catheter arrangement within an applicator to be determined, exploiting varying catheter orientations, heights, and curvatures if required. The pre-plan arrangement is then 3D printed to the exact specifications of the pre-plan applicator design. This results in improved target volume coverage and improved sparing of organs at risk. Using a pre-plan technique for ideal catheter placement followed by automated 3D-printed applicator manufacture has greatly improved the entire process of superficial high-dose-rate brachytherapy treatment. We are able to design and manufacture flexible, well-fitting, superior quality applicators resulting in a more efficient and improved patient pathway and patient experience. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Control Systems Engineering in Continuous Pharmaceutical Manufacturing May 20-21, 2014 Continuous Manufacturing Symposium.

PubMed

Myerson, Allan S; Krumme, Markus; Nasr, Moheb; Thomas, Hayden; Braatz, Richard D

2015-03-01

This white paper provides a perspective of the challenges, research needs, and future directions for control systems engineering in continuous pharmaceutical processing. The main motivation for writing this paper is to facilitate the development and deployment of control systems technologies so as to ensure quality of the drug product. Although the main focus is on small-molecule pharmaceutical products, most of the same statements apply to biological drug products. An introduction to continuous manufacturing and control systems is followed by a discussion of the current status and technical needs in process monitoring and control, systems integration, and risk analysis. Some key points are that: (1) the desired objective in continuous manufacturing should be the satisfaction of all critical quality attributes (CQAs), not for all variables to operate at steady-state values; (2) the design of start-up and shutdown procedures can significantly affect the economic operation of a continuous manufacturing process; (3) the traceability of material as it moves through the manufacturing facility is an important consideration that can at least in part be addressed using residence time distributions; and (4) the control systems technologies must assure quality in the presence of disturbances, dynamics, uncertainties, nonlinearities, and constraints. Direct measurement, first-principles and empirical model-based predictions, and design space approaches are described for ensuring that CQA specifications are met. Ways are discussed for universities, regulatory bodies, and industry to facilitate working around or through barriers to the development of control systems engineering technologies for continuous drug manufacturing. Industry and regulatory bodies should work with federal agencies to create federal funding mechanisms to attract faculty to this area. Universities should hire faculty interested in developing first-principles models and control systems technologies for drug manufacturing that are easily transportable to industry. Industry can facilitate the move to continuous manufacturing by working with universities on the conception of new continuous pharmaceutical manufacturing process unit operations that have the potential to make major improvements in product quality, controllability, or reduced capital and/or operating costs. Regulatory bodies should ensure that: (1) regulations and regulatory practices promote, and do not derail, the development and implementation of continuous manufacturing and control systems engineering approaches; (2) the individuals who approve specific regulatory filings are sufficiently trained to make good decisions regarding control systems approaches; (3) provide regulatory clarity and eliminate/reduce regulatory risks; (4) financially support the development of high-quality training materials for use of undergraduate students, graduate students, industrial employees, and regulatory staff; (5) enhance the training of their own technical staff by financially supporting joint research projects with universities in the development of continuous pharmaceutical manufacturing processes and the associated control systems engineering theory, numerical algorithms, and software; and (6) strongly encourage the federal agencies that support research to fund these research areas. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Control systems engineering in continuous pharmaceutical manufacturing. May 20-21, 2014 Continuous Manufacturing Symposium.

PubMed

Myerson, Allan S; Krumme, Markus; Nasr, Moheb; Thomas, Hayden; Braatz, Richard D

2015-03-01

This white paper provides a perspective of the challenges, research needs, and future directions for control systems engineering in continuous pharmaceutical processing. The main motivation for writing this paper is to facilitate the development and deployment of control systems technologies so as to ensure quality of the drug product. Although the main focus is on small-molecule pharmaceutical products, most of the same statements apply to biological drug products. An introduction to continuous manufacturing and control systems is followed by a discussion of the current status and technical needs in process monitoring and control, systems integration, and risk analysis. Some key points are that: (1) the desired objective in continuous manufacturing should be the satisfaction of all critical quality attributes (CQAs), not for all variables to operate at steady-state values; (2) the design of start-up and shutdown procedures can significantly affect the economic operation of a continuous manufacturing process; (3) the traceability of material as it moves through the manufacturing facility is an important consideration that can at least in part be addressed using residence time distributions; and (4) the control systems technologies must assure quality in the presence of disturbances, dynamics, uncertainties, nonlinearities, and constraints. Direct measurement, first-principles and empirical model-based predictions, and design space approaches are described for ensuring that CQA specifications are met. Ways are discussed for universities, regulatory bodies, and industry to facilitate working around or through barriers to the development of control systems engineering technologies for continuous drug manufacturing. Industry and regulatory bodies should work with federal agencies to create federal funding mechanisms to attract faculty to this area. Universities should hire faculty interested in developing first-principles models and control systems technologies for drug manufacturing that are easily transportable to industry. Industry can facilitate the move to continuous manufacturing by working with universities on the conception of new continuous pharmaceutical manufacturing process unit operations that have the potential to make major improvements in product quality, controllability, or reduced capital and/or operating costs. Regulatory bodies should ensure that: (1) regulations and regulatory practices promote, and do not derail, the development and implementation of continuous manufacturing and control systems engineering approaches; (2) the individuals who approve specific regulatory filings are sufficiently trained to make good decisions regarding control systems approaches; (3) provide regulatory clarity and eliminate/reduce regulatory risks; (4) financially support the development of high-quality training materials for use of undergraduate students, graduate students, industrial employees, and regulatory staff; (5) enhance the training of their own technical staff by financially supporting joint research projects with universities in the development of continuous pharmaceutical manufacturing processes and the associated control systems engineering theory, numerical algorithms, and software; and (6) strongly encourage the federal agencies that support research to fund these research areas. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Project-Based Manufacturing Engineering Practice at Ibaraki University and Its Outcomes

NASA Astrophysics Data System (ADS)

Yamasaki, Kazuhiko; Wang, Dong F.; Maekawa, Katsuhiro

The real world experience of manufacturing processes from an idea stage to a final product must be related to classroom lectures in mechanical engineering curriculum, including design, materials engineering, dynamics and control. Various challenges and difficulties encountered during the manufacturing engineering practice also let students recognize their creativity as well as what kinds of knowledge is missing. Awareness is the start of growth. In line with this principle we have carried out the mechanical engineering practice for 10 years. Some modifications toward “project-based practice” , however, have been made through manufacturing engineers’ real activities. Drawing and specification, process control, cost management, and role-sharing arrangement are stressed during the semester course. The present paper describes how it works and what is left to improve further, such as a refinement of themes and a coaching method for bringing out the hidden talent in students.

System Interdependency Modeling in the Design of Prognostic and Health Management Systems in Smart Manufacturing.

PubMed

Malinowski, M L; Beling, P A; Haimes, Y Y; LaViers, A; Marvel, J A; Weiss, B A

2015-01-01

The fields of risk analysis and prognostics and health management (PHM) have developed in a largely independent fashion. However, both fields share a common core goal. They aspire to manage future adverse consequences associated with prospective dysfunctions of the systems under consideration due to internal or external forces. This paper describes how two prominent risk analysis theories and methodologies - Hierarchical Holographic Modeling (HHM) and Risk Filtering, Ranking, and Management (RFRM) - can be adapted to support the design of PHM systems in the context of smart manufacturing processes. Specifically, the proposed methodologies will be used to identify targets - components, subsystems, or systems - that would most benefit from a PHM system in regards to achieving the following objectives: minimizing cost, minimizing production/maintenance time, maximizing system remaining usable life (RUL), maximizing product quality, and maximizing product output. HHM is a comprehensive modeling theory and methodology that is grounded on the premise that no system can be modeled effectively from a single perspective. It can also be used as an inductive method for scenario structuring to identify emergent forced changes (EFCs) in a system. EFCs connote trends in external or internal sources of risk to a system that may adversely affect specific states of the system. An important aspect of proactive risk management includes bolstering the resilience of the system for specific EFCs by appropriately controlling the states. Risk scenarios for specific EFCs can be the basis for the design of prognostic and diagnostic systems that provide real-time predictions and recognition of scenario changes. The HHM methodology includes visual modeling techniques that can enhance stakeholders' understanding of shared states, resources, objectives and constraints among the interdependent and interconnected subsystems of smart manufacturing systems. In risk analysis, HHM is often paired with Risk Filtering, Ranking, and Management (RFRM). The RFRM process provides the users, (e.g., technology developers, original equipment manufacturers (OEMs), technology integrators, manufacturers), with the most critical risks to the objectives, which can be used to identify the most critical components and subsystems that would most benefit from a PHM system. A case study is presented in which HHM and RFRM are adapted for PHM in the context of an active manufacturing facility located in the United States. The methodologies help to identify the critical risks to the manufacturing process, and the major components and subsystems that would most benefit from a developed PHM system.

System Interdependency Modeling in the Design of Prognostic and Health Management Systems in Smart Manufacturing

PubMed Central

Malinowski, M.L.; Beling, P.A.; Haimes, Y.Y.; LaViers, A.; Marvel, J.A.; Weiss, B.A.

2017-01-01

The fields of risk analysis and prognostics and health management (PHM) have developed in a largely independent fashion. However, both fields share a common core goal. They aspire to manage future adverse consequences associated with prospective dysfunctions of the systems under consideration due to internal or external forces. This paper describes how two prominent risk analysis theories and methodologies – Hierarchical Holographic Modeling (HHM) and Risk Filtering, Ranking, and Management (RFRM) – can be adapted to support the design of PHM systems in the context of smart manufacturing processes. Specifically, the proposed methodologies will be used to identify targets – components, subsystems, or systems – that would most benefit from a PHM system in regards to achieving the following objectives: minimizing cost, minimizing production/maintenance time, maximizing system remaining usable life (RUL), maximizing product quality, and maximizing product output. HHM is a comprehensive modeling theory and methodology that is grounded on the premise that no system can be modeled effectively from a single perspective. It can also be used as an inductive method for scenario structuring to identify emergent forced changes (EFCs) in a system. EFCs connote trends in external or internal sources of risk to a system that may adversely affect specific states of the system. An important aspect of proactive risk management includes bolstering the resilience of the system for specific EFCs by appropriately controlling the states. Risk scenarios for specific EFCs can be the basis for the design of prognostic and diagnostic systems that provide real-time predictions and recognition of scenario changes. The HHM methodology includes visual modeling techniques that can enhance stakeholders’ understanding of shared states, resources, objectives and constraints among the interdependent and interconnected subsystems of smart manufacturing systems. In risk analysis, HHM is often paired with Risk Filtering, Ranking, and Management (RFRM). The RFRM process provides the users, (e.g., technology developers, original equipment manufacturers (OEMs), technology integrators, manufacturers), with the most critical risks to the objectives, which can be used to identify the most critical components and subsystems that would most benefit from a PHM system. A case study is presented in which HHM and RFRM are adapted for PHM in the context of an active manufacturing facility located in the United States. The methodologies help to identify the critical risks to the manufacturing process, and the major components and subsystems that would most benefit from a developed PHM system. PMID:28664162

Selection and Manufacturing of Membrane Materials for Solar Sails

NASA Technical Reports Server (NTRS)

Bryant, Robert G.; Seaman, Shane T.; Wilkie, W. Keats; Miyaucchi, Masahiko; Working, Dennis C.

2013-01-01

Commercial metallized polyimide or polyester films and hand-assembly techniques are acceptable for small solar sail technology demonstrations, although scaling this approach to large sail areas is impractical. Opportunities now exist to use new polymeric materials specifically designed for solar sailing applications, and take advantage of integrated sail manufacturing to enable large-scale solar sail construction. This approach has, in part, been demonstrated on the JAXA IKAROS solar sail demonstrator, and NASA Langley Research Center is now developing capabilities to produce ultrathin membranes for solar sails by integrating resin synthesis with film forming and sail manufacturing processes. This paper will discuss the selection and development of polymer material systems for space, and these new processes for producing ultrathin high-performance solar sail membrane films.

Framework for Identifying Cybersecurity Risks in Manufacturing

DOE PAGES

Hutchins, Margot J.; Bhinge, Raunak; Micali, Maxwell K.; ...

2015-10-21

Increasing connectivity, use of digital computation, and off-site data storage provide potential for dramatic improvements in manufacturing productivity, quality, and cost. However, there are also risks associated with the increased volume and pervasiveness of data that are generated and potentially accessible to competitors or adversaries. Enterprises have experienced cyber attacks that exfiltrate confidential and/or proprietary data, alter information to cause an unexpected or unwanted effect, and destroy capital assets. Manufacturers need tools to incorporate these risks into their existing risk management processes. This article establishes a framework that considers the data flows within a manufacturing enterprise and throughout its supplymore » chain. The framework provides several mechanisms for identifying generic and manufacturing-specific vulnerabilities and is illustrated with details pertinent to an automotive manufacturer. Finally, in addition to providing manufacturers with insights into their potential data risks, this framework addresses an outcome identified by the NIST Cybersecurity Framework.« less

Framework for Identifying Cybersecurity Risks in Manufacturing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hutchins, Margot J.; Bhinge, Raunak; Micali, Maxwell K.

Increasing connectivity, use of digital computation, and off-site data storage provide potential for dramatic improvements in manufacturing productivity, quality, and cost. However, there are also risks associated with the increased volume and pervasiveness of data that are generated and potentially accessible to competitors or adversaries. Enterprises have experienced cyber attacks that exfiltrate confidential and/or proprietary data, alter information to cause an unexpected or unwanted effect, and destroy capital assets. Manufacturers need tools to incorporate these risks into their existing risk management processes. This article establishes a framework that considers the data flows within a manufacturing enterprise and throughout its supplymore » chain. The framework provides several mechanisms for identifying generic and manufacturing-specific vulnerabilities and is illustrated with details pertinent to an automotive manufacturer. Finally, in addition to providing manufacturers with insights into their potential data risks, this framework addresses an outcome identified by the NIST Cybersecurity Framework.« less

Sustainable Range Management of RDX and TNT by Phytoremediation with Engineered Plants

DTIC Science & Technology

2016-04-01

transformation products in the environment. Dinitrotoluenes are often co- contaminants at TNT- manufacturing sites, and dinitrotoluene-mineralizing bacteria...specific commercial product, process, or service by trade name, trademark, manufacturer , or otherwise, does not necessarily constitute or imply its...Distribution A 13. SUPPLEMENTARY NOTES 14. ABSTRACT Decades of military activity on live-fire training ranges have resulted in the contamination of

Lightweighting Automotive Materials for Increased Fuel Efficiency and Delivering Advanced Modeling and Simulation Capabilities to U.S. Manufacturers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hale, Steve

Abstract The National Center for Manufacturing Sciences (NCMS) worked with the U.S. Department of Energy (DOE), National Energy Technology Laboratory (NETL), to bring together research and development (R&D) collaborations to develop and accelerate the knowledgebase and infrastructure for lightweighting materials and manufacturing processes for their use in structural and applications in the automotive sector. The purpose/importance of this DOE program: • 2016 CAFÉ standards. • Automotive industry technology that shall adopt the insertion of lightweighting material concepts towards manufacturing of production vehicles. • Development and manufacture of advanced research tools for modeling and simulation (M&S) applications to reduce manufacturing andmore » material costs. • U.S. competitiveness that will help drive the development and manufacture of the next generation of materials. NCMS established a focused portfolio of applied R&D projects utilizing lightweighting materials for manufacture into automotive structures and components. Areas that were targeted in this program: • Functionality of new lightweighting materials to meet present safety requirements. • Manufacturability using new lightweighting materials. • Cost reduction for the development and use of new lightweighting materials. The automotive industry’s future continuously evolves through innovation, and lightweight materials are key in achieving a new era of lighter, more efficient vehicles. Lightweight materials are among the technical advances needed to achieve fuel/energy efficiency and reduce carbon dioxide (CO2) emissions: • Establish design criteria methodology to identify the best materials for lightweighting. • Employ state-of-the-art design tools for optimum material development for their specific applications. • Match new manufacturing technology to production volume. • Address new process variability with new production-ready processes.« less

Automated Cell Enrichment of Cytomegalovirus-specific T cells for Clinical Applications using the Cytokine-capture System.

PubMed

Kumaresan, Pappanaicken; Figliola, Mathew; Moyes, Judy S; Huls, M Helen; Tewari, Priti; Shpall, Elizabeth J; Champlin, Richard; Cooper, Laurence J N

2015-10-05

The adoptive transfer of pathogen-specific T cells can be used to prevent and treat opportunistic infections such as cytomegalovirus (CMV) infection occurring after allogeneic hematopoietic stem-cell transplantation. Viral-specific T cells from allogeneic donors, including third party donors, can be propagated ex vivo in compliance with current good manufacturing practice (cGMP), employing repeated rounds of antigen-driven stimulation to selectively propagate desired T cells. The identification and isolation of antigen-specific T cells can also be undertaken based upon the cytokine capture system of T cells that have been activated to secrete gamma-interferon (IFN-γ). However, widespread human application of the cytokine capture system (CCS) to help restore immunity has been limited as the production process is time-consuming and requires a skilled operator. The development of a second-generation cell enrichment device such as CliniMACS Prodigy now enables investigators to generate viral-specific T cells using an automated, less labor-intensive system. This device separates magnetically labeled cells from unlabeled cells using magnetic activated cell sorting technology to generate clinical-grade products, is engineered as a closed system and can be accessed and operated on the benchtop. We demonstrate the operation of this new automated cell enrichment device to manufacture CMV pp65-specific T cells obtained from a steady-state apheresis product obtained from a CMV seropositive donor. These isolated T cells can then be directly infused into a patient under institutional and federal regulatory supervision. All the bio-processing steps including removal of red blood cells, stimulation of T cells, separation of antigen-specific T cells, purification, and washing are fully automated. Devices such as this raise the possibility that T cells for human application can be manufactured outside of dedicated good manufacturing practice (GMP) facilities and instead be produced in blood banking facilities where staff can supervise automated protocols to produce multiple products.

Potential application of the consistency approach for vaccine potency testing.

PubMed

Arciniega, J; Sirota, L A

2012-01-01

The Consistency Approach offers the possibility of reducing the number of animals used for a potency test. However, it is critical to assess the effect that such reduction may have on assay performance. Consistency of production, sometimes referred to as consistency of manufacture or manufacturing, is an old concept implicit in regulation, which aims to ensure the uninterrupted release of safe and effective products. Consistency of manufacture can be described in terms of process capability, or the ability of a process to produce output within specification limits. For example, the standard method for potency testing of inactivated rabies vaccines is a multiple-dilution vaccination challenge test in mice that gives a quantitative, although highly variable estimate. On the other hand, a single-dilution test that does not give a quantitative estimate, but rather shows if the vaccine meets the specification has been proposed. This simplified test can lead to a considerable reduction in the number of animals used. However, traditional indices of process capability assume that the output population (potency values) is normally distributed, which clearly is not the case for the simplified approach. Appropriate computation of capability indices for the latter case will require special statistical considerations.

Method for automatically evaluating a transition from a batch manufacturing technique to a lean manufacturing technique

DOEpatents

Ivezic, Nenad; Potok, Thomas E.

2003-09-30

A method for automatically evaluating a manufacturing technique comprises the steps of: receiving from a user manufacturing process step parameters characterizing a manufacturing process; accepting from the user a selection for an analysis of a particular lean manufacturing technique; automatically compiling process step data for each process step in the manufacturing process; automatically calculating process metrics from a summation of the compiled process step data for each process step; and, presenting the automatically calculated process metrics to the user. A method for evaluating a transition from a batch manufacturing technique to a lean manufacturing technique can comprise the steps of: collecting manufacturing process step characterization parameters; selecting a lean manufacturing technique for analysis; communicating the selected lean manufacturing technique and the manufacturing process step characterization parameters to an automatic manufacturing technique evaluation engine having a mathematical model for generating manufacturing technique evaluation data; and, using the lean manufacturing technique evaluation data to determine whether to transition from an existing manufacturing technique to the selected lean manufacturing technique.

A methodology for Manufacturing Execution Systems (MES) implementation

NASA Astrophysics Data System (ADS)

Govindaraju, Rajesri; Putra, Krisna

2016-02-01

Manufacturing execution system is information systems (IS) application that bridges the gap between IS at the top level, namely enterprise resource planning (ERP), and IS at the lower levels, namely the automation systems. MES provides a media for optimizing the manufacturing process as a whole in a real time basis. By the use of MES in combination with the implementation of ERP and other automation systems, a manufacturing company is expected to have high competitiveness. In implementing MES, functional integration -making all the components of the manufacturing system able to work well together, is the most difficult challenge. For this, there has been an industry standard that specifies the sub-systems of a manufacturing execution systems and defines the boundaries between ERP systems, MES, and other automation systems. The standard is known as ISA-95. Although the advantages from the use of MES have been stated in some studies, not much research being done on how to implement MES effectively. The purpose of this study is to develop a methodology describing how MES implementation project should be managed, utilising the support of ISA- 95 reference model in the system development process. A proposed methodology was developed based on a general IS development methodology. The developed methodology were then revisited based on the understanding about the specific charateristics of MES implementation project found in an Indonesian steel manufacturing company implementation case. The case study highlighted the importance of applying an effective requirement elicitation method during innitial system assessment process, managing system interfaces and labor division in the design process, and performing a pilot deployment before putting the whole system into operation.

Architecture for distributed design and fabrication

NASA Astrophysics Data System (ADS)

McIlrath, Michael B.; Boning, Duane S.; Troxel, Donald E.

1997-01-01

We describe a flexible, distributed system architecture capable of supporting collaborative design and fabrication of semi-conductor devices and integrated circuits. Such capabilities are of particular importance in the development of new technologies, where both equipment and expertise are limited. Distributed fabrication enables direct, remote, physical experimentation in the development of leading edge technology, where the necessary manufacturing resources are new, expensive, and scarce. Computational resources, software, processing equipment, and people may all be widely distributed; their effective integration is essential in order to achieve the realization of new technologies for specific product requirements. Our architecture leverages is essential in order to achieve the realization of new technologies for specific product requirements. Our architecture leverages current vendor and consortia developments to define software interfaces and infrastructure based on existing and merging networking, CIM, and CAD standards. Process engineers and product designers access processing and simulation results through a common interface and collaborate across the distributed manufacturing environment.

Additive Manufacturing of Thermoplastic Matrix Composites Using Ultrasonics

NASA Astrophysics Data System (ADS)

Olson, Meghan

Advanced composite materials have great potential for facilitating energy efficient product design and their manufacture if improvements are made to current composite manufacturing processes. This thesis focuses on the development of a novel manufacturing process for thermoplastic composite structures entitled Laser-Ultrasonic Additive Manufacturing ('LUAM'), which is intended to combine the benefits of laser processing technology, developed by Automated Dynamics Inc., with ultrasonic bonding technology that is used commercially for unreinforced polymers. These technologies used together have the potential to significantly reduce the energy consumption and void content of thermoplastic composites made using Automated Fiber Placement (AFP). To develop LUAM in a methodical manner with minimal risk, a staged approach was devised whereby coupon-level mechanical testing and prototyping utilizing existing equipment was accomplished. Four key tasks have been identified for this effort: Benchmarking, Ultrasonic Compaction, Laser Assisted Ultrasonic Compaction, and Demonstration and Characterization of LUAM. This thesis specifically addresses Tasks 1 and 2, i.e. Benchmarking and Ultrasonic Compaction, respectively. Task 1, fabricating test specimens using two traditional processes (autoclave and thermal press) and testing structural performance and dimensional accuracy, provide results of a benchmarking study by which the performance of all future phases will be gauged. Task 2, fabricating test specimens using a non-traditional process (ultrasonic conpaction) and evaluating in a similar fashion, explores the the role of ultrasonic processing parameters using three different thermoplastic composite materials. Further development of LUAM, although beyond the scope of this thesis, will combine laser and ultrasonic technology and eventually demonstrate a working system.

Emission factors of air toxics from semiconductor manufacturing in Korea.

PubMed

Eom, Yun-Sung; Hong, Ji-Hyung; Lee, Suk-Jo; Lee, Eun-Jung; Cha, Jun-Seok; Lee, Dae-Gyun; Bang, Sun-Ae

2006-11-01

The development of local, accurate emission factors is very important for the estimation of reliable national emissions and air quality management. For that, this study is performed for pollutants released to the atmosphere with source-specific emission tests from the semiconductor manufacturing industry. The semiconductor manufacturing industry is one of the major sources of air toxics or hazardous air pollutants (HAPs); thus, understanding the emission characteristics of the emission source is a very important factor in the development of a control strategy. However, in Korea, there is a general lack of information available on air emissions from the semiconductor industry. The major emission sources of air toxics examined from the semiconductor manufacturing industry were wet chemical stations, coating applications, gaseous operations, photolithography, and miscellaneous devices in the wafer fabrication and semiconductor packaging processes. In this study, analyses of emission characteristics, and the estimations of emission data and factors for air toxics, such as acids, bases, heavy metals, and volatile organic compounds from the semiconductor manufacturing process have been performed. The concentration of hydrogen chloride from the packaging process was the highest among all of the processes. In addition, the emission factor of total volatile organic compounds (TVOCs) for the packaging process was higher than that of the wafer fabrication process. Emission factors estimated in this study were compared with those of Taiwan for evaluation, and they were found to be of similar level in the case of TVOCs and fluorine compounds.

21 CFR 184.1461 - Manganese sulfate.

Code of Federal Regulations, 2010 CFR

2010-04-01

... hydroquinone. Other manufacturing processes include the action of sulfur dioxide on a slurry of manganese..., followed by leaching and crystallization. (b) The ingredient meets the specifications of the Food Chemicals...

21 CFR 184.1461 - Manganese sulfate.

Code of Federal Regulations, 2011 CFR

2011-04-01

... hydroquinone. Other manufacturing processes include the action of sulfur dioxide on a slurry of manganese..., followed by leaching and crystallization. (b) The ingredient meets the specifications of the Food Chemicals...

WHO Expert Committee on specifications for pharmaceutical preparations.

PubMed

2010-01-01

The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use: good practices for pharmaceutical quality control laboratories; supplementary guidelines for active pharmaceutical ingredients; good manufacturing practices for pharmaceutical products containing hazardous substances; good manufacturing practices for sterile pharmaceutical products; good distribution practices for pharmaceutical products; guidelines on the requalification of prequalified dossiers: and guidelines for the preparation of a contract research organization master file.

Characterization of a Saccharomyces cerevisiae fermentation process for production of a therapeutic recombinant protein using a multivariate Bayesian approach.

PubMed

Fu, Zhibiao; Baker, Daniel; Cheng, Aili; Leighton, Julie; Appelbaum, Edward; Aon, Juan

2016-05-01

The principle of quality by design (QbD) has been widely applied to biopharmaceutical manufacturing processes. Process characterization is an essential step to implement the QbD concept to establish the design space and to define the proven acceptable ranges (PAR) for critical process parameters (CPPs). In this study, we present characterization of a Saccharomyces cerevisiae fermentation process using risk assessment analysis, statistical design of experiments (DoE), and the multivariate Bayesian predictive approach. The critical quality attributes (CQAs) and CPPs were identified with a risk assessment. The statistical model for each attribute was established using the results from the DoE study with consideration given to interactions between CPPs. Both the conventional overlapping contour plot and the multivariate Bayesian predictive approaches were used to establish the region of process operating conditions where all attributes met their specifications simultaneously. The quantitative Bayesian predictive approach was chosen to define the PARs for the CPPs, which apply to the manufacturing control strategy. Experience from the 10,000 L manufacturing scale process validation, including 64 continued process verification batches, indicates that the CPPs remain under a state of control and within the established PARs. The end product quality attributes were within their drug substance specifications. The probability generated with the Bayesian approach was also used as a tool to assess CPP deviations. This approach can be extended to develop other production process characterization and quantify a reliable operating region. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:799-812, 2016. © 2016 American Institute of Chemical Engineers.

The new production theory for health care through clinical reengineering: a study of clinical guidelines--Part II.

PubMed

Sharp, J R

1995-01-01

In Part I of this two-part article, in the December 1994 issue of the journal, the author discussed the manufacturing theories of Peter Drucker in terms of their applicability for the health care field. He concluded that Drucker's four principles and practices of manufacturing--statistical quality control, manufacturing accounting, modular organization, and systems approach--do have application to the health care system. Clinical guidelines, a variation on the Drucker theory, are a specific example of the manufacturing process in health. The performance to date of some guidelines and their implications for the health care reform debate are discussed in Part II of the article.

Comparison of electron beam and laser beam powder bed fusion additive manufacturing process for high temperature turbine component materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dryepondt, Sebastien N; Pint, Bruce A; Ryan, Daniel

2016-04-01

The evolving 3D printer technology is now at the point where some turbine components could be additive manufactured (AM) for both development and production purposes. However, this will require a significant evaluation program to qualify the process and components to meet current design and quality standards. The goal of the project was to begin characterization of the microstructure and mechanical properties of Nickel Alloy X (Ni-22Cr-18Fe-9Mo) test bars fabricated by powder bed fusion (PBF) AM processes that use either an electron beam (EB) or laser beam (LB) power source. The AM materials produced with the EB and LB processes displayedmore » significant differences in microstructure and resultant mechanical properties. Accordingly, during the design analysis of AM turbine components, the specific mechanical behavior of the material produced with the selected AM process should be considered. Comparison of the mechanical properties of both the EB and LB materials to those of conventionally processed Nickel Alloy X materials indicates the subject AM materials are viable alternatives for manufacture of some turbine components.« less

Application of response surface methodology to maximize the productivity of scalable automated human embryonic stem cell manufacture.

PubMed

Ratcliffe, Elizabeth; Hourd, Paul; Guijarro-Leach, Juan; Rayment, Erin; Williams, David J; Thomas, Robert J

2013-01-01

Commercial regenerative medicine will require large quantities of clinical-specification human cells. The cost and quality of manufacture is notoriously difficult to control due to highly complex processes with poorly defined tolerances. As a step to overcome this, we aimed to demonstrate the use of 'quality-by-design' tools to define the operating space for economic passage of a scalable human embryonic stem cell production method with minimal cell loss. Design of experiments response surface methodology was applied to generate empirical models to predict optimal operating conditions for a unit of manufacture of a previously developed automatable and scalable human embryonic stem cell production method. Two models were defined to predict cell yield and cell recovery rate postpassage, in terms of the predictor variables of media volume, cell seeding density, media exchange and length of passage. Predicted operating conditions for maximized productivity were successfully validated. Such 'quality-by-design' type approaches to process design and optimization will be essential to reduce the risk of product failure and patient harm, and to build regulatory confidence in cell therapy manufacturing processes.

Space system production cost benefits from contemporary philosophies in management and manufacturing

NASA Technical Reports Server (NTRS)

Rosmait, Russell L.

1991-01-01

The cost of manufacturing space system hardware has always been expensive. The Engineering Cost Group of the Program Planning office at Marshall is attempting to account for cost savings that result from new technologies in manufacturing and management. The objective is to identify and define contemporary philosophies in manufacturing and management. The seven broad categories that make up the areas where technological advances can assist in reducing space system costs are illustrated. Included within these broad categories is a list of the processes or techniques that specifically provide the cost savings within todays design, test, production and operations environments. The processes and techniques listed achieve savings in the following manner: increased productivity; reduced down time; reduced scrap; reduced rework; reduced man hours; and reduced material costs. In addition, it should be noted that cost savings from production and processing improvements effect 20 to 40 pct. of production costs whereas savings from management improvements effects 60 to 80 of production cost. This is important because most efforts in reducing costs are spent trying to reduce cost in the production.

EUV mask pilot line at Intel Corporation

NASA Astrophysics Data System (ADS)

Stivers, Alan R.; Yan, Pei-Yang; Zhang, Guojing; Liang, Ted; Shu, Emily Y.; Tejnil, Edita; Lieberman, Barry; Nagpal, Rajesh; Hsia, Kangmin; Penn, Michael; Lo, Fu-Chang

2004-12-01

The introduction of extreme ultraviolet (EUV) lithography into high volume manufacturing requires the development of a new mask technology. In support of this, Intel Corporation has established a pilot line devoted to encountering and eliminating barriers to manufacturability of EUV masks. It concentrates on EUV-specific process modules and makes use of the captive standard photomask fabrication capability of Intel Corporation. The goal of the pilot line is to accelerate EUV mask development to intersect the 32nm technology node. This requires EUV mask technology to be comparable to standard photomask technology by the beginning of the silicon wafer process development phase for that technology node. The pilot line embodies Intel's strategy to lead EUV mask development in the areas of the mask patterning process, mask fabrication tools, the starting material (blanks) and the understanding of process interdependencies. The patterning process includes all steps from blank defect inspection through final pattern inspection and repair. We have specified and ordered the EUV-specific tools and most will be installed in 2004. We have worked with International Sematech and others to provide for the next generation of EUV-specific mask tools. Our process of record is run repeatedly to ensure its robustness. This primes the supply chain and collects information needed for blank improvement.

Prion removal effect of a specific affinity ligand introduced into the manufacturing process of the pharmaceutical quality solvent/detergent (S/D)-treated plasma OctaplasLG.

PubMed

Neisser-Svae, A; Bailey, A; Gregori, L; Heger, A; Jordan, S; Behizad, M; Reichl, H; Römisch, J; Svae, T-E

2009-10-01

A new chromatographic step for the selective binding of abnormal prion protein (PrP(Sc)) was developed, and optimization for PrP(Sc) capture was achieved by binding to an affinity ligand attached to synthetic resin particles. This step was implemented into the manufacturing process of the solvent/detergent (S/D)-treated biopharmaceutical quality plasma Octaplas to further improve the safety margin in terms of risk for variant Creutzfeldt-Jakob disease (vCJD) transmission. Intermediates and Octaplas final container material, spiked with hamster brain-derived PrP(Sc)-containing fractions, were used for experiments to establish the feasibility of introducing this novel chromatography step. The binding capacity per millilitre of ligand gel was determined under the selected manufacturing conditions. In addition, the specificity of the ligand gel to bind PrP(Sc) from human sources was investigated. A validated Western blot test was used for the identification and quantification of PrP(Sc). A reduction factor of > or = 3.0 log(10) could be demonstrated by Western blotting, utilizing the relevant Octaplas matrix from manufacturing. In this particular cell-free plasma solution, the PrP(Sc) binding capacity of the selected gel was very high (> or = 6 log(10) ID(50)/ml, equivalent to roughly 10 log(10) ID(50)/column at manufacturing scale). The gel binds specifically PrP(Sc) from both animal (hamster and mouse) and human (sporadic and variant CJD) sources. This new single-use, disposable PrP(Sc)-harvesting gel ensures a very high capacity in terms of removing the pathogenic agent causing vCJD from the new generation OctaplasLG, in the event that prions can be found in plasma from donors incubating the disease and thereby contaminating the raw material plasma used for manufacturing.

Process-based Cost Estimation for Ramjet/Scramjet Engines

NASA Technical Reports Server (NTRS)

Singh, Brijendra; Torres, Felix; Nesman, Miles; Reynolds, John

2003-01-01

Process-based cost estimation plays a key role in effecting cultural change that integrates distributed science, technology and engineering teams to rapidly create innovative and affordable products. Working together, NASA Glenn Research Center and Boeing Canoga Park have developed a methodology of process-based cost estimation bridging the methodologies of high-level parametric models and detailed bottoms-up estimation. The NASA GRC/Boeing CP process-based cost model provides a probabilistic structure of layered cost drivers. High-level inputs characterize mission requirements, system performance, and relevant economic factors. Design alternatives are extracted from a standard, product-specific work breakdown structure to pre-load lower-level cost driver inputs and generate the cost-risk analysis. As product design progresses and matures the lower level more detailed cost drivers can be re-accessed and the projected variation of input values narrowed, thereby generating a progressively more accurate estimate of cost-risk. Incorporated into the process-based cost model are techniques for decision analysis, specifically, the analytic hierarchy process (AHP) and functional utility analysis. Design alternatives may then be evaluated not just on cost-risk, but also user defined performance and schedule criteria. This implementation of full-trade study support contributes significantly to the realization of the integrated development environment. The process-based cost estimation model generates development and manufacturing cost estimates. The development team plans to expand the manufacturing process base from approximately 80 manufacturing processes to over 250 processes. Operation and support cost modeling is also envisioned. Process-based estimation considers the materials, resources, and processes in establishing cost-risk and rather depending on weight as an input, actually estimates weight along with cost and schedule.

New Whole-House Solutions Case Study: Northwest Energy Efficient Manufactured Housing Program High-Performance Test Homes - Pacific Northwest

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2015-05-01

This project represents the third phase of a multi-year effort to develop and bring to market a High Performance Manufactured Home (HPMH). In this project, the Northwest Energy Efficient Manufactured Housing Program worked with Building America Partnership for Improved Residential Construction and Bonneville Power Administration to help four factory homebuilders build prototype zero energy ready manufactured homes, resulting in what is expected to be a 30% savings relative to the Building America Benchmark. (The actual % savings varies depending on choice of heating equipment and climate zone). Previous phases of this project created a HPMH specification and prototyped individual measuresmore » from the package to obtain engineering approvals and develop preliminary factory construction processes. This case study describes the project team's work during 2014 to build prototype homes to the HPMH specifications and to monitor the homes for energy performance and durability. Monitoring is expected to continue into 2016.« less

40 CFR 721.5 - Persons who must report.

Code of Federal Regulations, 2012 CFR

2012-07-01

... ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES General Provisions § 721.5 Persons who must report. (a... manufacture, import, or process for commercial purposes a chemical substance identified in a specific section... a chemical substance identified in a specific section in subpart E of this part, and intends to...

40 CFR 721.5 - Persons who must report.

Code of Federal Regulations, 2013 CFR

2013-07-01

... ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES General Provisions § 721.5 Persons who must report. (a... manufacture, import, or process for commercial purposes a chemical substance identified in a specific section... a chemical substance identified in a specific section in subpart E of this part, and intends to...

40 CFR 721.5 - Persons who must report.

Code of Federal Regulations, 2011 CFR

2011-07-01

... ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES General Provisions § 721.5 Persons who must report. (a... manufacture, import, or process for commercial purposes a chemical substance identified in a specific section... a chemical substance identified in a specific section in subpart E of this part, and intends to...

40 CFR 721.5 - Persons who must report.

Code of Federal Regulations, 2014 CFR

2014-07-01

... ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES General Provisions § 721.5 Persons who must report. (a... manufacture, import, or process for commercial purposes a chemical substance identified in a specific section... a chemical substance identified in a specific section in subpart E of this part, and intends to...

49 CFR 178.39 - Specification 3BN seamless nickel cylinders.

Code of Federal Regulations, 2013 CFR

2013-10-01

... manufactured using equipment and processes adequate to ensure that each cylinder produced conforms to the.... A reasonably smooth and uniform surface finish is required. Cylinders closed in by spinning process... plugs, etc.) for those openings. Threads conforming to the following are required on openings: (1...

49 CFR 178.39 - Specification 3BN seamless nickel cylinders.

Code of Federal Regulations, 2014 CFR

2014-10-01

... manufactured using equipment and processes adequate to ensure that each cylinder produced conforms to the.... A reasonably smooth and uniform surface finish is required. Cylinders closed in by spinning process... plugs, etc.) for those openings. Threads conforming to the following are required on openings: (1...

49 CFR 178.39 - Specification 3BN seamless nickel cylinders.

Code of Federal Regulations, 2012 CFR

2012-10-01

... manufactured using equipment and processes adequate to ensure that each cylinder produced conforms to the.... A reasonably smooth and uniform surface finish is required. Cylinders closed in by spinning process... plugs, etc.) for those openings. Threads conforming to the following are required on openings: (1...

77 FR 8884 - Draft Guidance for Industry on Quality Considerations in Demonstrating Biosimilarity to a...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-15

... information (e.g., characterization, adventitious agent safety, process controls, and specifications) for the... Manufacturing Process Assessment of Physiochemical Properties Functional Activities Receptor Binding and... 351(k) application. FDA will also seek OMB approval for this information collection. In addition, this...

Integrated Process Modeling-A Process Validation Life Cycle Companion.

PubMed

Zahel, Thomas; Hauer, Stefan; Mueller, Eric M; Murphy, Patrick; Abad, Sandra; Vasilieva, Elena; Maurer, Daniel; Brocard, Cécile; Reinisch, Daniela; Sagmeister, Patrick; Herwig, Christoph

2017-10-17

During the regulatory requested process validation of pharmaceutical manufacturing processes, companies aim to identify, control, and continuously monitor process variation and its impact on critical quality attributes (CQAs) of the final product. It is difficult to directly connect the impact of single process parameters (PPs) to final product CQAs, especially in biopharmaceutical process development and production, where multiple unit operations are stacked together and interact with each other. Therefore, we want to present the application of Monte Carlo (MC) simulation using an integrated process model (IPM) that enables estimation of process capability even in early stages of process validation. Once the IPM is established, its capability in risk and criticality assessment is furthermore demonstrated. IPMs can be used to enable holistic production control strategies that take interactions of process parameters of multiple unit operations into account. Moreover, IPMs can be trained with development data, refined with qualification runs, and maintained with routine manufacturing data which underlines the lifecycle concept. These applications will be shown by means of a process characterization study recently conducted at a world-leading contract manufacturing organization (CMO). The new IPM methodology therefore allows anticipation of out of specification (OOS) events, identify critical process parameters, and take risk-based decisions on counteractions that increase process robustness and decrease the likelihood of OOS events.

Emerging technology: A key enabler for modernizing pharmaceutical manufacturing and advancing product quality.

PubMed

O'Connor, Thomas F; Yu, Lawrence X; Lee, Sau L

2016-07-25

Issues in product quality have produced recalls and caused drug shortages in United States (U.S.) in the past few years. These quality issues were often due to outdated manufacturing technologies and equipment as well as lack of an effective quality management system. To ensure consistent supply of safe, effective and high-quality drug products available to the patients, the U.S. Food and Drug Administration (FDA) supports modernizing pharmaceutical manufacturing for improvements in product quality. Specifically, five new initiatives are proposed here to achieve this goal. They include: (i) advancing regulatory science for pharmaceutical manufacturing; (ii) establishing a public-private institute for pharmaceutical manufacturing innovation; (iii) creating incentives for investment in the technological upgrade of manufacturing processes and facilities; (iv) leveraging external expertise for regulatory quality assessment of emerging technologies; and (v) promoting the international harmonization of approaches for expediting the global adoption of emerging technologies. Published by Elsevier B.V.

Structural Integrity of an Electron Beam Melted Titanium Alloy.

PubMed

Lancaster, Robert; Davies, Gareth; Illsley, Henry; Jeffs, Spencer; Baxter, Gavin

2016-06-14

Advanced manufacturing encompasses the wide range of processes that consist of "3D printing" of metallic materials. One such method is Electron Beam Melting (EBM), a modern build technology that offers significant potential for lean manufacture and a capability to produce fully dense near-net shaped components. However, the manufacture of intricate geometries will result in variable thermal cycles and thus a transient microstructure throughout, leading to a highly textured structure. As such, successful implementation of these technologies requires a comprehensive assessment of the relationships of the key process variables, geometries, resultant microstructures and mechanical properties. The nature of this process suggests that it is often difficult to produce representative test specimens necessary to achieve a full mechanical property characterisation. Therefore, the use of small scale test techniques may be exploited, specifically the small punch (SP) test. The SP test offers a capability for sampling miniaturised test specimens from various discrete locations in a thin-walled component, allowing a full characterisation across a complex geometry. This paper provides support in working towards development and validation strategies in order for advanced manufactured components to be safely implemented into future gas turbine applications. This has been achieved by applying the SP test to a series of Ti-6Al-4V variants that have been manufactured through a variety of processing routes including EBM and investigating the structural integrity of each material and how this controls the mechanical response.

Analysis of form deviation in non-isothermal glass molding

NASA Astrophysics Data System (ADS)

Kreilkamp, H.; Grunwald, T.; Dambon, O.; Klocke, F.

2018-02-01

Especially in the market of sensors, LED lighting and medical technologies, there is a growing demand for precise yet low-cost glass optics. This demand poses a major challenge for glass manufacturers who are confronted with the challenge arising from the trend towards ever-higher levels of precision combined with immense pressure on market prices. Since current manufacturing technologies especially grinding and polishing as well as Precision Glass Molding (PGM) are not able to achieve the desired production costs, glass manufacturers are looking for alternative technologies. Non-isothermal Glass Molding (NGM) has been shown to have a big potential for low-cost mass manufacturing of complex glass optics. However, the biggest drawback of this technology at the moment is the limited accuracy of the manufactured glass optics. This research is addressing the specific challenges of non-isothermal glass molding with respect to form deviation of molded glass optics. Based on empirical models, the influencing factors on form deviation in particular form accuracy, waviness and surface roughness will be discussed. A comparison with traditional isothermal glass molding processes (PGM) will point out the specific challenges of non-isothermal process conditions. Furthermore, the underlying physical principle leading to the formation of form deviations will be analyzed in detail with the help of numerical simulation. In this way, this research contributes to a better understanding of form deviations in non-isothermal glass molding and is an important step towards new applications demanding precise yet low-cost glass optics.

Application of Terahertz Attenuated Total Reflection Spectroscopy to Detect Changes in the Physical Properties of Lactose during the Lubrication Process Required for Drug Formulation.

PubMed

Dohi, Masafumi; Momose, Wataru; Yamashita, Kazunari; Hakomori, Tadashi; Sato, Shusaku; Noguchi, Shuji; Terada, Katsuhide

2017-02-01

Manufacturing the solid dosage form of an orally administered drug requires lubrication to enhance manufacturability, ensuring that critical quality attributes such as disintegration and dissolution of the drug product are maintained during manufacture. Here, to evaluate lubrication performance during manufacture, we used terahertz attenuated total reflection (THz-ATR) spectroscopy to detect differences in the physical characteristics of the lubricated powder. We applied a simple formulation prepared by blending granulated lactose as filler with magnesium stearate as lubricant. A flat tablet was prepared using the lubricated powder to acquire sharp THz-ATR absorption peaks of the samples. First, we investigated the effects of lubricant concentration and compression pressure on preparation of the tablet and then determined the effect of the pressure applied to samples in contact with the ATR prism on sample absorption amplitude. We focused on the differences in the magnitudes of spectra at the lactose-specific frequency. Second, we conducted the dynamic lubrication process using a 120-L mixer to investigate differences in the magnitudes of absorption corresponding to the lactose-specific frequency during lubrication. In both studies, enriching the lubricated powder with a higher concentration of magnesium stearate or prolonging blending time correlated with higher magnitudes of spectra at the lactose-specific frequency. Further, in the dynamic lubrication study, the wettability and disintegration time of the tablets were compared with the absorption spectra amplitudes at the lactose-specific frequency. We conclude that THz-ATR spectroscopy is useful for detecting differences in densities caused by a change in the physical properties of lactose during lubrication.

Space processing: A projection

NASA Technical Reports Server (NTRS)

Mccreight, L. R.; Griffin, R. N.

1972-01-01

Estimates concerning space manufacturing, which might well become the largest and most specific application of space technology by the end of the century are given. Two classes of materials are considered - electronic crystals and biologicals.

49 CFR 178.55 - Specification 4B240ET welded or brazed cylinders.

Code of Federal Regulations, 2012 CFR

2012-10-01

.... (a) Type, spinning process, size and service pressure. A DOT 4B240ET cylinder is a brazed type... process are authorized. (b) Steel. Open-hearth, basic oxygen, or electric steel of uniform quality must be... manufactured using equipment and processes adequate to ensure that each cylinder produced conforms to the...

49 CFR 178.61 - Specification 4BW welded steel cylinders with electric-arc welded longitudinal seam.

Code of Federal Regulations, 2014 CFR

2014-10-01

.... Cylinders closed in by spinning process are not authorized. (b) Authorized steel. Steel used in the.... Cylinders must be manufactured using equipment and processes adequate to ensure that each cylinder produced... seams must be of the butt welded type. Welds must be made by a machine process including automatic feed...

49 CFR 178.55 - Specification 4B240ET welded or brazed cylinders.

Code of Federal Regulations, 2013 CFR

2013-10-01

.... (a) Type, spinning process, size and service pressure. A DOT 4B240ET cylinder is a brazed type... process are authorized. (b) Steel. Open-hearth, basic oxygen, or electric steel of uniform quality must be... manufactured using equipment and processes adequate to ensure that each cylinder produced conforms to the...

49 CFR 178.61 - Specification 4BW welded steel cylinders with electric-arc welded longitudinal seam.

Code of Federal Regulations, 2013 CFR

2013-10-01

.... Cylinders closed in by spinning process are not authorized. (b) Authorized steel. Steel used in the.... Cylinders must be manufactured using equipment and processes adequate to ensure that each cylinder produced... seams must be of the butt welded type. Welds must be made by a machine process including automatic feed...

49 CFR 178.55 - Specification 4B240ET welded or brazed cylinders.

Code of Federal Regulations, 2014 CFR

2014-10-01

.... (a) Type, spinning process, size and service pressure. A DOT 4B240ET cylinder is a brazed type... process are authorized. (b) Steel. Open-hearth, basic oxygen, or electric steel of uniform quality must be... manufactured using equipment and processes adequate to ensure that each cylinder produced conforms to the...

49 CFR 178.61 - Specification 4BW welded steel cylinders with electric-arc welded longitudinal seam.

Code of Federal Regulations, 2012 CFR

2012-10-01

.... Cylinders closed in by spinning process are not authorized. (b) Authorized steel. Steel used in the.... Cylinders must be manufactured using equipment and processes adequate to ensure that each cylinder produced... seams must be of the butt welded type. Welds must be made by a machine process including automatic feed...

49 CFR 178.55 - Specification 4B240ET welded or brazed cylinders.

Code of Federal Regulations, 2011 CFR

2011-10-01

.... (a) Type, spinning process, size and service pressure. A DOT 4B240ET cylinder is a brazed type... process are authorized. (b) Steel. Open-hearth, basic oxygen, or electric steel of uniform quality must be... manufactured using equipment and processes adequate to ensure that each cylinder produced conforms to the...

Vaccine provision: Delivering sustained & widespread use.

PubMed

Preiss, Scott; Garçon, Nathalie; Cunningham, Anthony L; Strugnell, Richard; Friedland, Leonard R

2016-12-20

The administration of a vaccine to a recipient is the final step in a development and production process that may have begun several decades earlier. Here we describe the scale and complexity of the processes that brings a candidate vaccine through clinical development to the recipient. These challenges include ensuring vaccine quality (between 100 and 500 different Quality Control tests are performed during production to continually assess safety, potency and purity); making decisions about optimal vaccine presentation (pre-filled syringes versus multi-dose vials) that affect capacity and supply; and the importance of maintaining the vaccine cold chain (most vaccines have stringent storage temperature requirements necessary to maintain activity and potency). The ultimate aim is to make sure that an immunogenic product matching the required specifications reaches the recipient. The process from concept to licensure takes 10-30years. Vaccine licensure is based on a file submitted to regulatory agencies which contains the comprehensive compilation of chemistry, manufacturing information, assay procedures, preclinical and clinical trial results, and proposals for post-licensure effectiveness and safety data collection. Expedited development and licensure pathways may be sought in emergency settings: e.g., the 2009 H1N1 influenza pandemic, the 2014 West African Ebola outbreak and meningococcal serogroup B meningitis outbreaks in the United States and New Zealand. Vaccines vary in the complexity of their manufacturing process. Influenza vaccines are particularly challenging to produce and delays in manufacturing may occur, leading to vaccine shortages during the influenza season. Shortages can be difficult to resolve due to long manufacturing lead times and stringent, but variable, local regulations. New technologies are driving the development of new vaccines with simplified manufacturing requirements and with quality specifications that can be confirmed with fewer tests. These technologies could have far-reaching effects on supply, cost of goods, and on response timing to a medical need until product availability. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Statistical Process Control: Going to the Limit for Quality.

ERIC Educational Resources Information Center

Training, 1987

1987-01-01

Defines the concept of statistical process control, a quality control method used especially in manufacturing. Generally, concept users set specific standard levels that must be met. Makes the point that although employees work directly with the method, management is responsible for its success within the plant. (CH)

21 CFR 660.21 - Processing.

Code of Federal Regulations, 2010 CFR

2010-04-01

... STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Blood Grouping Reagent § 660.21 Processing. (a... representative samples of each group of products manufactured in the same fashion. (2) Only that material that... specifications to verify that each sublot is identical to other sublots of the lot. (4) Each lot of Blood...

Monitoring of staphylococcal starters in two French processing plants manufacturing dry fermented sausages.

PubMed

Corbiere Morot-Bizot, S; Leroy, S; Talon, R

2007-01-01

The growth and survival of Staphylococcus xylosus and Staphylococcus carnosus were monitored during sausage manufacture in two processing plants. The gram-positive, catalase-positive cocci isolated from the processing plants F10 and F11 were identified by Staphylococcus-specific PCR and species-specific oligonucleotide array. In the inoculated products with starter cultures, 90% of staphylococcal strains isolated in F10 were identified as S. xylosus and 10% as S. carnosus. In F11, 77% were identified as S. xylosus and 20% as S. carnosus. Staphylococcus xylosus dominated the staphylococcal microbiota while S. carnosus survived during the process. The pulse-field gel electrophoresis analysis revealed that all S. xylosus and S. carnosus strains isolated corresponded to the starter strains inoculated. The two starter strains of S. xylosus co-dominated in the isolates from sausages of F11, whereas the strain with pattern A1 was dominant in the isolates from sausages of F10. In the environments, no S. carnosus and S. xylosus were found, whereas Staphylococcus equorum and Staphylococcus saprophyticus were the main species isolated. This work highlighted the domination of S. xylosus starter strains, which showed a strong capacity to grow during sausage process, while S. carnosus survived during the process. Successful implantation of starter cultures is obviously a prerequisite for their contribution to sensorial qualities. Thus, the monitoring of the growth and the survival of S. xylosus and S. carnosus are required to guarantee a well-adapted starter culture. This study revealed that the two Staphylococcus species are suitable for manufacturing sausages in processing plants with very different capacities of production.

Manufacturing and fabrication, part 3. [extraterrestrial resources

NASA Technical Reports Server (NTRS)

Sastri, Sankar; Duke, Michael B.; Haskin, Larry A.

1992-01-01

The accessibility of material and energy off the Earth and the leverage that these nonterrestrial resources can exert on the space transportation system are important influences on the long-term goal of exploring the solar system. Research on separation of lunar materials and manufacturing of useful products from them is in its infancy. A few possible processes and products are described in this report. Specific attention is given to oxygen, metal, and silicate products.

Additive Manufacturing of Multifunctional Components Using High Density Carbon Nanotube Yarn Filaments

NASA Technical Reports Server (NTRS)

Gardner, John M.; Sauti, Godfrey; Kim, Jae-Woo; Cano, Roberto J.; Wincheski, Russell A.; Stelter, Christopher J.; Grimsley, Brian W.; Working, Dennis C.; Siochi, Emilie J.

2016-01-01

Additive manufacturing allows for design freedom and part complexity not currently attainable using traditional manufacturing technologies. Fused Filament Fabrication (FFF), for example, can yield novel component geometries and functionalities because the method provides a high level of control over material placement and processing conditions. This is achievable by extrusion of a preprocessed filament feedstock material along a predetermined path. However if fabrication of a multifunctional part relies only on conventional filament materials, it will require a different material for each unique functionality printed into the part. Carbon nanotubes (CNTs) are an attractive material for many applications due to their high specific strength as well as good electrical and thermal conductivity. The presence of this set of properties in a single material presents an opportunity to use one material to achieve multifunctionality in an additively manufactured part. This paper describes a recently developed method for processing continuous CNT yarn filaments into three-dimensional articles, and summarizes the mechanical, electrical, and sensing performance of the components fabricated in this way.

Fabrication of light water reactor tritium targets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pilger, J.P.

1991-11-01

The mission of the Fabrication Development Task of the Tritium Target Development Project is: to produce a documented technology basis, including specifications and procedures for target rod fabrication; to demonstrate that light water tritium targets can be manufactured at a rate consistent with tritium production requirements; and to develop quality control methods to evaluate target rod components and assemblies, and establish correlations between evaluated characteristics and target rod performance. Many of the target rod components: cladding tubes, end caps, plenum springs, etc., have similar counterparts in LWR fuel rods. High production rate manufacture and inspection of these components has beenmore » adequately demonstrated by nuclear fuel rod manufacturers. This summary describes the more non-conventional manufacturing processes and inspection techniques developed to fabricate target rod components whose manufacturability at required production rates had not been previously demonstrated.« less

Modular Hydropower Engineering and Pilot Scale Manufacturing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chesser, Phillip C.

Emrgy has developed, prototyped and tested a modular hydropower system for renewable energy generation. ORNL worked with Emrgy to demonstrate the use of additive manufacturing in the production of the hydrofoils and spokes for the hydrokinetic system. Specifically, during Phase 1 of this effort, ORNL printed and finished machined patterns for both the hydrofoils and spokes that were subsequently used in a sand casting manufacturing process. Emrgy utilized the sand castings for a pilot installation in Denver, CO, where the parts represented an 80% cost savings from the previous prototype build that was manufactured using subtractive manufacturing. In addition, themore » castings were completed with ORNL’s newly developed AlCeMg alloy that will be tested for performance improvements including higher corrosion resistance in a water application than the 6160 alloy used previously« less

In-Space Manufacturing Baseline Property Development

NASA Technical Reports Server (NTRS)

Stockman, Tom; Schneider, Judith; Prater, Tracie; Bean, Quincy; Werkheiser, Nicki

2016-01-01

The In-Space Manufacturing (ISM) project at NASA Marshall Space Flight Center currently operates a 3D FDM (fused deposition modeling) printer onboard the International Space Station. In order to enable utilization of this capability by designer, the project needs to establish characteristic material properties for materials produced using the process. This is difficult for additive manufacturing since standards and specifications do not yet exist for these technologies. Due to availability of crew time, there are limitations to the sample size which in turn limits the application of the traditional design allowables approaches to develop a materials property database for designers. In this study, various approaches to development of material databases were evaluated for use by designers of space systems who wish to leverage in-space manufacturing capabilities. This study focuses on alternative statistical techniques for baseline property development to support in-space manufacturing.

An evaluation of alternative cleaning methods for removing an organic contaminant from a stainless steel part

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boyd, J.L.

1996-08-01

As of December 1995, the manufacture of Freon, along with many other chlorofluorocarbons (CFCs), was prohibited by the Clean Air Act of 1990 (CAA). The ban of CFC solvents has forced manufacturers across the country to search for alternative metal cleaning techniques. The objective of this study was to develop a thorough, scientific based approach for resolving one specific manufacturer`s problem of removing organic contamination from a stainless steel part. This objective was accomplished with an approach that involved: (1) defining the problem, (2) identifying the process constraints, (3) researching alternate cleaning methods, (4) researching applicable government regulations, (5) performingmore » a scientific evaluation and (6) drawing conclusions.« less

Development of novel IVD assays: a manufacturer's perspective.

PubMed

Metcalfe, Thomas A

2010-01-01

IVD manufacturers are heavily reliant on novel IVD assays to fuel their growth and drive innovation within the industry. They represent a key part of the IVD industry's value proposition to customers and the healthcare industry in general, driving product differentiation, helping to create demand for new systems and generating incremental revenue. However, the discovery of novel biomarkers and their qualification for a specific clinical purpose is a high risk undertaking and the large, risky investments associated with doing this on a large scale are incompatible with IVD manufacturer's business models. This article describes the sources of novel IVD assays, the processes for discovering and qualifying novel assays and the reliance of IVD manufacturers on collaborations and in-licensing to source new IVD assays for their platforms.

Evaluation of genetic polymorphism among Lactobacillus rhamnosus non-starter Parmigiano Reggiano cheese strains.

PubMed

Bove, Claudio Giorgio; De Dea Lindner, Juliano; Lazzi, Camilla; Gatti, Monica; Neviani, Erasmo

2011-01-05

Parmigiano Reggiano (PR) is an Italian cooked, long-ripened cheese made with unheated cow's milk and natural whey starter. The microflora is involved in the manufacturing of this cheese, arising from the natural whey starter, the raw milk and the environment. Molecular studies have shown that mesophilic non-starter lactic acid bacteria (NSLAB) are the dominant microflora present during the ripening of PR. In this study, a characterisation of Lactobacillus rhamnosus isolated from a single PR manufacturing and ripening process is reported, using a combination of genotypic fingerprinting techniques (RAPD-PCR and REP-PCR). The intraspecies heterogeneity evidenced for 66 strains is correlated to their abilities to adapt to specific environmental and technological conditions. The detection of biotypes that correlate with specific moments in cheese ripening or differential development throughout this process suggests that these strains may have specific roles closely linked to their peculiar technological properties. Copyright © 2010 Elsevier B.V. All rights reserved.

3D Systems' Technology Overview and New Applications in Manufacturing, Engineering, Science, and Education

PubMed Central

Andrews, Mike; Weislogel, Mark; Moeck, Peter; Stone-Sundberg, Jennifer; Birkes, Derek; Hoffert, Madeline Paige; Lindeman, Adam; Morrill, Jeff; Fercak, Ondrej; Friedman, Sasha; Gunderson, Jeff; Ha, Anh; McCollister, Jack; Chen, Yongkang; Geile, John; Wollman, Andrew; Attari, Babak; Botnen, Nathan; Vuppuluri, Vasant; Shim, Jennifer; Kaminsky, Werner; Adams, Dustin; Graft, John

2014-01-01

Abstract Since the inception of 3D printing, an evolutionary process has taken place in which specific user and customer needs have crossed paths with the capabilities of a growing number of machines to create value-added businesses. Even today, over 30 years later, the growth of 3D printing and its utilization for the good of society is often limited by the various users' understanding of the technology for their specific needs. This article presents an overview of current 3D printing technologies and shows numerous examples from a multitude of fields from manufacturing to education. PMID:28473997

Integrating Materials, Manufacturing, Design and Validation for Sustainability in Future Transport Systems

NASA Astrophysics Data System (ADS)

Price, M. A.; Murphy, A.; Butterfield, J.; McCool, R.; Fleck, R.

2011-05-01

The predictive methods currently used for material specification, component design and the development of manufacturing processes, need to evolve beyond the current `metal centric' state of the art, if advanced composites are to realise their potential in delivering sustainable transport solutions. There are however, significant technical challenges associated with this process. Deteriorating environmental, political, economic and social conditions across the globe have resulted in unprecedented pressures to improve the operational efficiency of the manufacturing sector generally and to change perceptions regarding the environmental credentials of transport systems in particular. There is a need to apply new technologies and develop new capabilities to ensure commercial sustainability in the face of twenty first century economic and climatic conditions as well as transport market demands. A major technology gap exists between design, analysis and manufacturing processes in both the OEMs, and the smaller companies that make up the SME based supply chain. As regulatory requirements align with environmental needs, manufacturers are increasingly responsible for the broader lifecycle aspects of vehicle performance. These include not only manufacture and supply but disposal and re-use or re-cycling. In order to make advances in the reduction of emissions coupled with improved economic efficiency through the provision of advanced lightweight vehicles, four key challenges are identified as follows: Material systems, Manufacturing systems, Integrated design methods using digital manufacturing tools and Validation systems. This paper presents a project which has been designed to address these four key issues, using at its core, a digital framework for the creation and management of key parameters related to the lifecycle performance of thermoplastic composite parts and structures. It aims to provide capability for the proposition, definition, evaluation and demonstration of advanced lightweight structures for new generation vehicles in the context of whole life performance parameters.

Case Studies in Modelling, Control in Food Processes.

PubMed

Glassey, J; Barone, A; Montague, G A; Sabou, V

This chapter discusses the importance of modelling and control in increasing food process efficiency and ensuring product quality. Various approaches to both modelling and control in food processing are set in the context of the specific challenges in this industrial sector and latest developments in each area are discussed. Three industrial case studies are used to demonstrate the benefits of advanced measurement, modelling and control in food processes. The first case study illustrates the use of knowledge elicitation from expert operators in the process for the manufacture of potato chips (French fries) and the consequent improvements in process control to increase the consistency of the resulting product. The second case study highlights the economic benefits of tighter control of an important process parameter, moisture content, in potato crisp (chips) manufacture. The final case study describes the use of NIR spectroscopy in ensuring effective mixing of dry multicomponent mixtures and pastes. Practical implementation tips and infrastructure requirements are also discussed.

49 CFR 178.274 - Specifications for UN portable tanks.

Code of Federal Regulations, 2014 CFR

2014-10-01

... welding of pressure vessels. When the manufacturing process or the materials make it necessary, the shells... strength of the tubing, such as may happen when cutting threads. Brazed joints are not authorized for...

49 CFR 178.274 - Specifications for UN portable tanks.

Code of Federal Regulations, 2012 CFR

2012-10-01

... welding of pressure vessels. When the manufacturing process or the materials make it necessary, the shells... strength of the tubing, such as may happen when cutting threads. Brazed joints are not authorized for...

Assessment of Intelligent Processing Equipment in the National Aeronautics and Space Administration, 1991

NASA Technical Reports Server (NTRS)

Jones, C. S.

1992-01-01

Summarized here is an assessment of intelligent processing equipment (IPE) within NASA. An attempt is made to determine the state of IPE development and research in specific areas where NASA might contribute to the national capability. Mechanisms to transfer NASA technology to the U.S. private sector in this critical area are discussed. It was concluded that intelligent processing equipment is finding extensive use in the manufacture of space hardware, especially in the propulsion components of the shuttle. The major benefits are found in improved process consistency, which lowers cost as it reduces rework. Advanced feedback controls are under development and being implemented gradually into shuttle manufacturing. Implementation is much more extensive in new programs, such as in the advanced solid rocket motor and the Space Station Freedom.

Patient-Specific Surgical Implants Made of 3D Printed PEEK: Material, Technology, and Scope of Surgical Application

PubMed Central

Okolo, Brando; Popp, Uwe

2018-01-01

Additive manufacturing (AM) is rapidly gaining acceptance in the healthcare sector. Three-dimensional (3D) virtual surgical planning, fabrication of anatomical models, and patient-specific implants (PSI) are well-established processes in the surgical fields. Polyetheretherketone (PEEK) has been used, mainly in the reconstructive surgeries as a reliable alternative to other alloplastic materials for the fabrication of PSI. Recently, it has become possible to fabricate PEEK PSI with Fused Filament Fabrication (FFF) technology. 3D printing of PEEK using FFF allows construction of almost any complex design geometry, which cannot be manufactured using other technologies. In this study, we fabricated various PEEK PSI by FFF 3D printer in an effort to check the feasibility of manufacturing PEEK with 3D printing. Based on these preliminary results, PEEK can be successfully used as an appropriate biomaterial to reconstruct the surgical defects in a “biomimetic” design. PMID:29713642

Patient-Specific Surgical Implants Made of 3D Printed PEEK: Material, Technology, and Scope of Surgical Application.

PubMed

Honigmann, Philipp; Sharma, Neha; Okolo, Brando; Popp, Uwe; Msallem, Bilal; Thieringer, Florian M

2018-01-01

Additive manufacturing (AM) is rapidly gaining acceptance in the healthcare sector. Three-dimensional (3D) virtual surgical planning, fabrication of anatomical models, and patient-specific implants (PSI) are well-established processes in the surgical fields. Polyetheretherketone (PEEK) has been used, mainly in the reconstructive surgeries as a reliable alternative to other alloplastic materials for the fabrication of PSI. Recently, it has become possible to fabricate PEEK PSI with Fused Filament Fabrication (FFF) technology. 3D printing of PEEK using FFF allows construction of almost any complex design geometry, which cannot be manufactured using other technologies. In this study, we fabricated various PEEK PSI by FFF 3D printer in an effort to check the feasibility of manufacturing PEEK with 3D printing. Based on these preliminary results, PEEK can be successfully used as an appropriate biomaterial to reconstruct the surgical defects in a "biomimetic" design.

Advanced Infusion Techniques with 3-D Printed Tooling

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nuttall, David; Elliott, Amy; Post, Brian K.

The manufacturing of tooling for large, contoured surfaces for fiber-layup applications requires significant effort to understand the geometry and then to subtractively manufacture the tool. Traditional methods for the auto industry use clay that is hand sculpted. In the marine pleasure craft industry, the exterior of the model is formed from a foam lay-up that is either hand cut or machined to create smooth lines. Engineers and researchers at Oak Ridge National Laboratory s Manufacturing Demonstration Facility (ORNL MDF) collaborated with Magnum Venus Products (MVP) in the development of a process for reproducing legacy whitewater adventure craft via digital scanningmore » and large scale 3-D printed layup molds. The process entailed 3D scanning a legacy canoe form, converting that form to a CAD model, additively manufacturing (3-D Print) the mold tool, and subtractively finishing the mold s transfer surfaces. Future work will include applying a gelcoat to the mold transfer surface and infusing using vacuum assisted resin transfer molding, or VARTM principles, to create a watertight vessel. The outlined steps were performed on a specific canoe geometry found by MVP s principal participant. The intent of utilizing this geometry is to develop an energy efficient and marketable process for replicating complex shapes, specifically focusing on this particular watercraft, and provide a finished product for demonstration to the composites industry. The culminating part produced through this agreement has been slated for public presentation and potential demonstration at the 2016 CAMX (Composites and Advanced Materials eXpo) exposition in Anaheim, CA. Phase I of this collaborative research and development agreement (MDF-15-68) was conducted under CRADA NFE-15-05575 and was initiated on May 7, 2015, with an introduction to the MVP product line, and concluded in March of 2016 with the printing of and processing of a canoe mold. The project partner Magnum Venous Products (MVP) is a small business. Phase II as discussed herein is under consideration by MVP as of this writing. Overall, it is anticipated that developing this process for manufacturing tooling for complex contoured surfaces has applicability to naval and other watercraft as well as bathrooms and large trucks.« less

19 CFR 191.8 - Specific manufacturing drawback ruling.

Code of Federal Regulations, 2010 CFR

2010-04-01

... manufacturing drawback ruling. Where a separately-incorporated subsidiary of a parent corporation is engaged in manufacture or production for drawback, the subsidiary is the proper party to apply for a specific... specific manufacturing drawback ruling shall be submitted, in triplicate, to CBP Headquarters (Attention...

Second Aerospace Environmental Technology Conference

NASA Technical Reports Server (NTRS)

Whitaker, A. F. (Editor); Clark-Ingram, M. (Editor)

1997-01-01

The mandated elimination of CFC'S, Halons, TCA, and other ozone depleting chemicals and specific hazardous materials has required changes and new developments in aerospace materials and processes. The aerospace industry has been involved for several years in providing product substitutions, redesigning entire production processes, and developing new materials that minimize or eliminate damage to the environment. These activities emphasize replacement cleaning solvents and their application, verification, compliant coatings including corrosion protection system and removal techniques, chemical propulsion effects on the environment, and the initiation of modifications to relevant processing and manufacturing specifications and standards.

Second Aerospace Environmental Technology Conference

NASA Technical Reports Server (NTRS)

Whitaker, A. F.; Clark-Ingram, M.; Hessler, S. L.

1997-01-01

The mandated elimination of CFC's, Halons, TCA, and other ozone depleting chemicals and specific hazardous materials has required changes and new developments in aerospace materials and processes. The aerospace industry has been involved for several years in providing product substitutions, redesigning entire production processes, and developing new materials that minimize or eliminate damage to the environment. These activities emphasize replacement cleaning solvents and their application verifications, compliant coatings including corrosion protection systems, and removal techniques, chemical propulsion effects on the environment, and the initiation of modifications to relevant processing and manufacturing specifications and standards.

Long-term health experience of jet engine manufacturing workers: VIII. glioblastoma incidence in relation to workplace experiences with parts and processes.

PubMed

Marsh, Gary M; Youk, Ada O; Buchanich, Jeanine M; Downing, Sarah; Kennedy, Kathleen J; Esmen, Nurtan A; Hancock, Roger P; Lacey, Steven E; Pierce, Jennifer S; Fleissner, Mary Lou

2013-06-01

To determine whether glioblastoma (GB) incidence rates among jet engine manufacturing workers were associated with workplace experiences with specific parts produced and processes performed. Subjects were 210,784 workers employed between 1952 and 2001. We conducted nested case-control and cohort incidence studies with focus on 277 GB cases. We estimated time experienced with 16 part families, 4 process categories, and 32 concurrent part-process combinations with 20 or more GB cases. In both the cohort and case-control studies, none of the part families, process categories, or both considered was associated with increased GB risk. If not due to chance alone, the not statistically significantly elevated GB rates in the North Haven plant may reflect external occupational factors or nonoccupational factors unmeasured in the current evaluation.

Lignin-Derived Advanced Carbon Materials

DOE PAGES

Chatterjee, Sabornie; Saito, Tomonori

2015-11-16

Lignin is a highly abundant source of renewable carbon that can be considered as a valuable sustainable source of biobased materials. By applying specific pretreatments and manufacturing methods, it has been found that lignin can be converted into a variety of value-added carbon materials. However, the physical and chemical heterogeneities of lignin complicate its use as a feedstock. Herein, we discuss the lignin manufacturing process, the effects of pretreatments and manufacturing methods on the properties of product lignin, and structure–property relationships in various applications of lignin-derived carbon materials, such as carbon fibers, carbon mats, activated carbons, carbon films, and templatedmore » carbon.« less

Lignin-Derived Advanced Carbon Materials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chatterjee, Sabornie; Saito, Tomonori

Lignin is a highly abundant source of renewable carbon that can be considered as a valuable sustainable source of biobased materials. By applying specific pretreatments and manufacturing methods, it has been found that lignin can be converted into a variety of value-added carbon materials. However, the physical and chemical heterogeneities of lignin complicate its use as a feedstock. Herein, we discuss the lignin manufacturing process, the effects of pretreatments and manufacturing methods on the properties of product lignin, and structure–property relationships in various applications of lignin-derived carbon materials, such as carbon fibers, carbon mats, activated carbons, carbon films, and templatedmore » carbon.« less

How Many Batches Are Needed for Process Validation under the New FDA Guidance?

PubMed

Yang, Harry

2013-01-01

The newly updated FDA Guidance for Industry on Process Validation: General Principles and Practices ushers in a life cycle approach to process validation. While the guidance no longer considers the use of traditional three-batch validation appropriate, it does not prescribe the number of validation batches for a prospective validation protocol, nor does it provide specific methods to determine it. This potentially could leave manufacturers in a quandary. In this paper, I develop a Bayesian method to address the issue. By combining process knowledge gained from Stage 1 Process Design (PD) with expected outcomes of Stage 2 Process Performance Qualification (PPQ), the number of validation batches for PPQ is determined to provide a high level of assurance that the process will consistently produce future batches meeting quality standards. Several examples based on simulated data are presented to illustrate the use of the Bayesian method in helping manufacturers make risk-based decisions for Stage 2 PPQ, and they highlight the advantages of the method over traditional Frequentist approaches. The discussions in the paper lend support for a life cycle and risk-based approach to process validation recommended in the new FDA guidance. The newly updated FDA Guidance for Industry on Process Validation: General Principles and Practices ushers in a life cycle approach to process validation. While the guidance no longer considers the use of traditional three-batch validation appropriate, it does not prescribe the number of validation batches for a prospective validation protocol, nor does it provide specific methods to determine it. This potentially could leave manufacturers in a quandary. In this paper, I develop a Bayesian method to address the issue. By combining process knowledge gained from Stage 1 Process Design (PD) with expected outcomes of Stage 2 Process Performance Qualification (PPQ), the number of validation batches for PPQ is determined to provide a high level of assurance that the process will consistently produce future batches meeting quality standards. Several examples based on simulated data are presented to illustrate the use of the Bayesian method in helping manufacturers make risk-based decisions for Stage 2 PPQ, and THEY highlight the advantages of the method over traditional Frequentist approaches. The discussions in the paper lend support for a life cycle and risk-based approach to process validation recommended in the new FDA guidance.

Structural Integrity of an Electron Beam Melted Titanium Alloy

PubMed Central

Lancaster, Robert; Davies, Gareth; Illsley, Henry; Jeffs, Spencer; Baxter, Gavin

2016-01-01

Advanced manufacturing encompasses the wide range of processes that consist of “3D printing” of metallic materials. One such method is Electron Beam Melting (EBM), a modern build technology that offers significant potential for lean manufacture and a capability to produce fully dense near-net shaped components. However, the manufacture of intricate geometries will result in variable thermal cycles and thus a transient microstructure throughout, leading to a highly textured structure. As such, successful implementation of these technologies requires a comprehensive assessment of the relationships of the key process variables, geometries, resultant microstructures and mechanical properties. The nature of this process suggests that it is often difficult to produce representative test specimens necessary to achieve a full mechanical property characterisation. Therefore, the use of small scale test techniques may be exploited, specifically the small punch (SP) test. The SP test offers a capability for sampling miniaturised test specimens from various discrete locations in a thin-walled component, allowing a full characterisation across a complex geometry. This paper provides support in working towards development and validation strategies in order for advanced manufactured components to be safely implemented into future gas turbine applications. This has been achieved by applying the SP test to a series of Ti-6Al-4V variants that have been manufactured through a variety of processing routes including EBM and investigating the structural integrity of each material and how this controls the mechanical response. PMID:28773590

Manufacturing history of etanercept (Enbrel®): Consistency of product quality through major process revisions.

PubMed

Hassett, Brian; Singh, Ena; Mahgoub, Ehab; O'Brien, Julie; Vicik, Steven M; Fitzpatrick, Brian

2018-01-01

Etanercept (ETN) (Enbrel®) is a soluble protein that binds to, and specifically inhibits, tumor necrosis factor (TNF), a proinflammatory cytokine. ETN is synthesized in Chinese hamster ovary cells by recombinant DNA technology as a fusion protein, with a fully human TNFRII ectodomain linked to the Fc portion of human IgG1. Successful manufacture of biologics, such as ETN, requires sophisticated process and product understanding, as well as meticulous control of operations to maintain product consistency. The objective of this evaluation was to show that the product profile of ETN drug substance (DS) has been consistent over the course of production. Multiple orthogonal biochemical analyses, which included evaluation of attributes indicative of product purity, potency, and quality, were assessed on >2,000 batches of ETN from three sites of DS manufacture, during the period 1998-2015. Based on the key quality attributes of product purity (assessed by hydrophobic interaction chromatography HPLC), binding activity (to TNF by ELISA), potency (inhibition of TNF-induced apoptosis by cell-based bioassay) and quality (N-linked oligosaccharide map), we show that the integrity of ETN DS has remained consistent over time. This consistency was maintained through three major enhancements to the initial process of manufacturing that were supported by detailed comparability assessments, and approved by the European Medicines Agency. Examination of results for all major quality attributes for ETN DS indicates a highly consistent process for over 18 years and throughout changes to the manufacturing process, without affecting safety and efficacy, as demonstrated across a wide range of clinical trials of ETN in multiple inflammatory diseases.

48 CFR 952.227-13 - Patent rights-acquisition by the Government.

Code of Federal Regulations, 2011 CFR

2011-10-01

... a process or method; or to operate, in the case of a machine or system; and, in each case, under... procedures. (2) If the Contracting Officer learns of an unreported Contractor invention which the Contracting... upon the practice of any specific process, method, machine, manufacture, or composition of matter...

48 CFR 952.227-13 - Patent rights-acquisition by the Government.

Code of Federal Regulations, 2010 CFR

2010-10-01

... a process or method; or to operate, in the case of a machine or system; and, in each case, under... procedures. (2) If the Contracting Officer learns of an unreported Contractor invention which the Contracting... upon the practice of any specific process, method, machine, manufacture, or composition of matter...

49 CFR 178.47 - Specification 4DS welded stainless steel cylinders for aircraft use.

Code of Federal Regulations, 2013 CFR

2013-10-01

... be manufactured using equipment and processes adequate to ensure that each cylinder produced conforms... °F ±25° after process treatment and before hydrostatic test. (h) Openings in container. Openings must... a fitting, boss, or pad must be adequate to prevent leakage. Threads must comply with the following...

49 CFR 178.47 - Specification 4DS welded stainless steel cylinders for aircraft use.

Code of Federal Regulations, 2012 CFR

2012-10-01

... be manufactured using equipment and processes adequate to ensure that each cylinder produced conforms... °F ±25° after process treatment and before hydrostatic test. (h) Openings in container. Openings must... a fitting, boss, or pad must be adequate to prevent leakage. Threads must comply with the following...

49 CFR 178.47 - Specification 4DS welded stainless steel cylinders for aircraft use.

Code of Federal Regulations, 2014 CFR

2014-10-01

... be manufactured using equipment and processes adequate to ensure that each cylinder produced conforms... °F ±25° after process treatment and before hydrostatic test. (h) Openings in container. Openings must... a fitting, boss, or pad must be adequate to prevent leakage. Threads must comply with the following...

Stabilized thermally beneficiated low rank coal and method of manufacture

DOEpatents

Viall, Arthur J.; Richards, Jeff M.

1999-01-01

A process for reducing the spontaneous combustion tendencies of thermally beneficiated low rank coals employing heat, air or an oxygen containing gas followed by an optional moisture addition. Specific reaction conditions are supplied along with knowledge of equipment types that may be employed on a commercial scale to complete the process.

Stabilized thermally beneficiated low rank coal and method of manufacture

DOEpatents

Viall, Arthur J.; Richards, Jeff M.

2000-01-01

A process for reducing the spontaneous combustion tendencies of thermally beneficiated low rank coals employing heat, air or an oxygen containing gas followed by an optional moisture addition. Specific reaction conditions are supplied along with knowledge of equipment types that may be employed on a commercial scale to complete the process.

48 CFR 952.227-13 - Patent rights-acquisition by the Government.

Code of Federal Regulations, 2014 CFR

2014-10-01

... a process or method; or to operate, in the case of a machine or system; and, in each case, under... procedures. (2) If the Contracting Officer learns of an unreported Contractor invention which the Contracting... upon the practice of any specific process, method, machine, manufacture, or composition of matter...

48 CFR 952.227-13 - Patent rights-acquisition by the Government.

Code of Federal Regulations, 2013 CFR

2013-10-01

... a process or method; or to operate, in the case of a machine or system; and, in each case, under... procedures. (2) If the Contracting Officer learns of an unreported Contractor invention which the Contracting... upon the practice of any specific process, method, machine, manufacture, or composition of matter...

48 CFR 952.227-13 - Patent rights-acquisition by the Government.

Code of Federal Regulations, 2012 CFR

2012-10-01

... a process or method; or to operate, in the case of a machine or system; and, in each case, under... procedures. (2) If the Contracting Officer learns of an unreported Contractor invention which the Contracting... upon the practice of any specific process, method, machine, manufacture, or composition of matter...

Sensors for process control Focus Team report

NASA Astrophysics Data System (ADS)

At the Semiconductor Technology Workshop, held in November 1992, the Semiconductor Industry Association (SIA) convened 179 semiconductor technology experts to assess the 15-year outlook for the semiconductor manufacturing industry. The output of the Workshop, a document entitled 'Semiconductor Technology: Workshop Working Group Reports,' contained an overall roadmap for the technology characteristics envisioned in integrated circuits (IC's) for the period 1992-2007. In addition, the document contained individual roadmaps for numerous key areas in IC manufacturing, such as film deposition, thermal processing, manufacturing systems, exposure technology, etc. The SIA Report did not contain a separate roadmap for contamination free manufacturing (CFM). A key component of CFM for the next 15 years is the use of sensors for (1) defect reduction, (2) improved product quality, (3) improved yield, (4) improved tool utilization through contamination reduction, and (5) real time process control in semiconductor fabrication. The objective of this Focus Team is to generate a Sensors for Process Control Roadmap. Implicit in this objective is the identification of gaps in current sensor technology so that research and development activity in the sensor industry can be stimulated to develop sensor systems capable of meeting the projected roadmap needs. Sensor performance features of interest include detection limit, specificity, sensitivity, ease of installation and maintenance, range, response time, accuracy, precision, ease and frequency of calibration, degree of automation, and adaptability to in-line process control applications.

An Assessment of Nondestructive Evaluation Capability for Complex Additive Manufacturing Aerospace Components

NASA Technical Reports Server (NTRS)

Walker, James; Beshears, Ron; Lambert, Dennis; Tilson, William

2016-01-01

The primary focus of this work is to investigate some of the fundamental relationships between processing, mechanical testing, materials characterization, and NDE for additively manufactured (AM) components using the powder bed fusion direct melt laser sintered process. The goal is to understand the criticality of defects unique to the AM process and then how conventional nondestructive evaluation methods as well as some of the more non-traditional methods such as computed tomography, are effected by the AM material. Specific defects including cracking, porosity and partially/unfused powder will be addressed. Besides line-of-site NDE, as appropriate these inspection capabilities will be put into the context of complex AM geometries where hidden features obscure, or inhibit traditional NDE methods.

Microstructure and Magnetic Properties of Magnetic Material Fabricated by Selective Laser Melting

NASA Astrophysics Data System (ADS)

Jhong, Kai Jyun; Huang, Wei-Chin; Lee, Wen Hsi

Selective Laser Melting (SLM) is a powder-based additive manufacturing which is capable of producing parts layer-by-layer from a 3D CAD model. The aim of this study is to adopt the selective laser melting technique to magnetic material fabrication. [1]For the SLM process to be practical in industrial use, highly specific mechanical properties of the final product must be achieved. The integrity of the manufactured components depend strongly on each single laser-melted track and every single layer, as well as the strength of the connections between them. In this study, effects of the processing parameters, such as the space distance of surface morphology is analyzed. Our hypothesis is that when a magnetic product is made by the selective laser melting techniques instead of traditional techniques, the finished component will have more precise and effective properties. This study analyzed the magnitudes of magnetic properties in comparison with different parameters in the SLM process and compiled a completed product to investigate the efficiency in contrast with products made with existing manufacturing processes.

Synthesis and characterization of Ti-27.5Nb alloy made by CLAD® additive manufacturing process for biomedical applications.

PubMed

Fischer, M; Laheurte, P; Acquier, P; Joguet, D; Peltier, L; Petithory, T; Anselme, K; Mille, P

2017-06-01

Biocompatible beta-titanium alloys such as Ti-27.5(at.%)Nb are good candidates for implantology and arthroplasty applications as their particular mechanical properties, including low Young's modulus, could significantly reduce the stress-shielding phenomenon usually occurring after surgery. The CLAD® process is a powder blown additive manufacturing process that allows the manufacture of patient specific (i.e. custom) implants. Thus, the use of Ti-27.5(at.%)Nb alloy formed by CLAD® process for biomedical applications as a mean to increase cytocompatibility and mechanical biocompatibility was investigated in this study. The microstructural properties of the CLAD-deposited alloy were studied with optical microscopy and electron back-scattered diffraction (EBSD) analysis. The conservation of the mechanical properties of the Ti-27.5Nb material after the transformation steps (ingot-powder atomisation-CLAD) were verified with tensile tests and appear to remain close to those of reference material. Cytocompatibility of the material and subsequent cell viability tests showed that no cytotoxic elements are released in the medium and that viable cells proliferated well. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of Processing and Medical Sterilization Techniques on 3D-Printed and Molded Polylactic Acid

NASA Astrophysics Data System (ADS)

Geritano, Mariah Nicole

Manufacturing industries have evolved tremendously in the past decade with the introduction of Additive Manufacturing (AM), also known as 3D Printing. The medical device industry has been a leader in adapting this new technology into research and development. 3D printing enables medical devices and implants to become more customizable, patient specific, and allows for low production numbers. This study compares the mechanical and thermal properties of traditionally manufactured parts versus parts manufactured through 3D printing before and after sterilization, and the ability of an FDM printer to produce reliable, identical samples. It was found that molded samples and 100% infill high-resolution samples have almost identical changes in properties when exposed to different sterilization methods, and similar cooling rates. The data shown throughout this investigation confirms that manipulation of printing parameters can result in an object with comparable material properties to that created through traditional manufacturing methods.

Small Scale Turbopump Manufacturing Technology and Material Processes

NASA Technical Reports Server (NTRS)

Alvarez, Erika; Morgan, Kristin; Wells, Doug; Zimmerman, Frank

2011-01-01

As part of an internal research and development project, NASA Marshall Space Flight Center (MSFC) has been developing a high specific impulse 9,000-lbf LOX/LH2 pump-fed engine testbed with the capability to throttle 10:1. A Fuel Turbopump (FTP) with the ability to operate across a speed range of 30,000-rpm to 100,000-rpm was developed and analyzed. This small size and flight-like Fuel Turbopump has completed the design and analysis phase and is currently in the manufacturing phase. This paper highlights the manufacturing and processes efforts to fabricate an approximately 20-lb turbopump with small flow passages, intricately bladed components and approximately 3-in diameter impellers. As a result of the small scale and tight tolerances of the hardware on this turbopump, several unique manufacturing and material challenges were encountered. Some of the technologies highlighted in this paper include the use of powder metallurgy technology to manufacture small impellers, electron beam welding of a turbine blisk shroud, and casting challenges. The use of risk reduction efforts such as non-destructive testing (NDT) and evaluation (NDE), fractography, material testing, and component spin testing are also discussed in this paper.

78 FR 12067 - Extreme Weather Effects on Medical Device Safety and Quality

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-21

... medicines at home, and dialysis machines in outpatient centers. The specific risks to patients and the best... impacted your manufacturing site? What were the lessons learned during the recovery process as you returned...

Cleaning of parts for new manufacturing and parts rebuilding

NASA Astrophysics Data System (ADS)

Doherty, Jeff

1994-06-01

Parts cleaning is the largest single expense, and the most time consuming activity, in rebuilding and new manufacturing. On average, 25% to 40% of the total labor and overhead burden is spent on cleaning. EPA and OSHA pressures add to the burden by making some methods and chemicals obsolete. Some of the processes and chemicals in current use will be curtailed and or outlawed in the future. How can a shops and industries make long term decisions or capital investments in cleaning and process improvements when the government keeps changing its rules? At the MART Corporation in Saint Louis, Missouri, we manufacture a line of cabinet-style batch cleaning machines known as Power Washers. Twenty years ago MART invented and patented the Power Washer process, a cleaning method that recycles wash solution and blasts contaminates as they are washed off the more heavily contaminated parts. Since the initial invention MART has continued to R&D the washing process and develop ancillary systems that comply with EPA and OSHA regulations. For applications involving new industrial parts or items requiring specification cleaned surfaces. MART provides filtration and solution conditioning systems, part drying operations, and triple rinsing. Units are available in stainless steel or higher alloys. We are not alone in the washer manufacturing business. You have many choices of cleaning solutions (no pun intended) which will perform in your operations and yield good results. As a manufacturer, we are interested in your success with our equipment. We have all heard the horror stories of companies having selected inappropriate cleaning systems and or processes which then brought the company to its knees, production wise. Assembly, appearance, warranty, and performance shortcomings of finished products can often be directly related to the cleaning process and its shortcomings.

Predictive modeling, simulation, and optimization of laser processing techniques: UV nanosecond-pulsed laser micromachining of polymers and selective laser melting of powder metals

NASA Astrophysics Data System (ADS)

Criales Escobar, Luis Ernesto

One of the most frequently evolving areas of research is the utilization of lasers for micro-manufacturing and additive manufacturing purposes. The use of laser beam as a tool for manufacturing arises from the need for flexible and rapid manufacturing at a low-to-mid cost. Laser micro-machining provides an advantage over mechanical micro-machining due to the faster production times of large batch sizes and the high costs associated with specific tools. Laser based additive manufacturing enables processing of powder metals for direct and rapid fabrication of products. Therefore, laser processing can be viewed as a fast, flexible, and cost-effective approach compared to traditional manufacturing processes. Two types of laser processing techniques are studied: laser ablation of polymers for micro-channel fabrication and selective laser melting of metal powders. Initially, a feasibility study for laser-based micro-channel fabrication of poly(dimethylsiloxane) (PDMS) via experimentation is presented. In particular, the effectiveness of utilizing a nanosecond-pulsed laser as the energy source for laser ablation is studied. The results are analyzed statistically and a relationship between process parameters and micro-channel dimensions is established. Additionally, a process model is introduced for predicting channel depth. Model outputs are compared and analyzed to experimental results. The second part of this research focuses on a physics-based FEM approach for predicting the temperature profile and melt pool geometry in selective laser melting (SLM) of metal powders. Temperature profiles are calculated for a moving laser heat source to understand the temperature rise due to heating during SLM. Based on the predicted temperature distributions, melt pool geometry, i.e. the locations at which melting of the powder material occurs, is determined. Simulation results are compared against data obtained from experimental Inconel 625 test coupons fabricated at the National Institute for Standards & Technology via response surface methodology techniques. The main goal of this research is to develop a comprehensive predictive model with which the effect of powder material properties and laser process parameters on the built quality and integrity of SLM-produced parts can be better understood. By optimizing process parameters, SLM as an additive manufacturing technique is not only possible, but also practical and reproducible.

Additive manufacturing of scaffolds with dexamethasone controlled release for enhanced bone regeneration.

PubMed

Costa, Pedro F; Puga, Ana M; Díaz-Gomez, Luis; Concheiro, Angel; Busch, Dirk H; Alvarez-Lorenzo, Carmen

2015-12-30

The adoption of additive manufacturing in tissue engineering and regenerative medicine (TERM) strategies greatly relies on the development of novel 3D printable materials with advanced properties. In this work we have developed a material for bone TERM applications with tunable bioerosion rate and dexamethasone release profile which can be further employed in fused deposition modelling (the most common and accessible 3D printing technology in the market). The developed material consisted of a blend of poly-ϵ-caprolactone (PCL) and poloxamine (Tetronic®) and was processed into a ready-to-use filament form by means of a simplified melt-based methodology, therefore eliminating the utilization of solvents. 3D scaffolds composed of various blend formulations were additively manufactured and analyzed revealing blend ratio-specific degradation rates and dexamethasone release profiles. Furthermore, in vitro culture studies revealed a similar blend ratio-specific trend concerning the osteoinductive activity of the fabricated scaffolds when these were seeded and cultured with human mesenchymal stem cells. The developed material enables to specifically address different regenerative requirements found in various tissue defects. The versatility of such strategy is further increased by the ability of additive manufacturing to accurately fabricate implants matching any given defect geometry. Copyright © 2015 Elsevier B.V. All rights reserved.

Update On The Development, Testing, And Manufacture Of High Density LEU-Foil Targets For The Production Of Mo-99

DOE Office of Scientific and Technical Information (OSTI.GOV)

Creasy, John T

2015-05-12

This project has the objective to reduce and/or eliminate the use of HEU in commerce. Steps in the process include developing a target testing methodology that is bounding for all Mo-99 target irradiators, establishing a maximum target LEU-foil mass, developing a LEU-foil target qualification document, developing a bounding target failure analysis methodology (failure in reactor containment), optimizing safety vs. economics (goal is to manufacture a safe, but relatively inexpensive target to offset the inherent economic disadvantage of using LEU in place of HEU), and developing target material specifications and manufacturing QC test criteria. The slide presentation is organized under themore » following topics: Objective, Process Overview, Background, Team Structure, Key Achievements, Experiment and Activity Descriptions, and Conclusions. The High Density Target project has demonstrated: approx. 50 targets irradiated through domestic and international partners; proof of concept for two front end processing methods; fabrication of uranium foils for target manufacture; quality control procedures and steps for manufacture; multiple target assembly techniques; multiple target disassembly devices; welding of targets; thermal, hydraulic, and mechanical modeling; robust target assembly parametric studies; and target qualification analysis for insertion into very high flux environment. The High Density Target project has tested and proven several technologies that will benefit current and future Mo-99 producers.« less

An Innovative Manufacturing of CCC Ion Thruster Grids by North Carolina A&T's RTM Carbon/Carbon Process

NASA Technical Reports Server (NTRS)

Haag, Thomas W. (Technical Monitor); Shivakumar, Kunigal N.

2003-01-01

Electric ion thrusters are the preferred engines for deep space missions, because of very high specific impulse. The ion engine consists of screen and accelerator grids containing thousands of concentric very small holes. The xenon gas accelerates between the two grids, thus developing the impulse force. The dominant life-limiting mechanism in the state-of-the-art molybdenum thrusters is the xenon ion sputter erosion of the accelerator grid. Carbon/carbon composites (CCC) have shown to be have less than 1/7 the erosion rates than the molybdenum, thus for interplanetary missions CCC engines are inevitable. Early effort to develop CCC composite thrusters had a limited success because of limitations of the drilling technology and the damage caused by drilling. The proposed is an in-situ manufacturing of holes while the CCC is made. Special low CTE molds will be used along with the NC A&T s patented resin transfer molding (RTM) technology to manufacture the CCC grids. First, a manufacture process for 10-cm diameter thruster grids will be developed and verified. Quality of holes, density, CTE, tension, flexure, transverse fatigue and sputter yield properties will be measured. After establishing the acceptable quality and properties, the process will be scaled to manufacture 30-cm diameter grids. The properties of the two grid sizes are compared with each other.

High-power ultrasonic processing: Recent developments and prospective advances

NASA Astrophysics Data System (ADS)

Gallego-Juarez, Juan A.

2010-01-01

Although the application of ultrasonic energy to produce or to enhance a wide variety of processes have been explored since about the middle of the 20th century, only a reduced number of ultrasonic processes have been established at industrial level. However, during the last ten years the interest in ultrasonic processing has revived particularly in industrial sectors where the ultrasonic technology may represent a clean and efficient tool to improve classical existing processes or an innovation alternative for the development of new processes. Such seems to be the case of relevant sectors such as food industry, environment, pharmaceuticals and chemicals manufacture, machinery, mining, etc where power ultrasound is becoming an emerging technology for process development. The possible major problem in the application of high-intensity ultrasound on industrial processing is the design and development of efficient power ultrasonic systems (generators and reactors) capable of large scale successful operation specifically adapted to each individual process. In the area of ultrasonic processing in fluid media and more specifically in gases, the development of the steppedplate transducers and other power ge with extensive radiating surface has strongly contributed to the implementation at semi-industrial and industrial stage of several commercial applications, in sectors such as food and beverage industry (defoaming, drying, extraction, etc), environment (air cleaning, sludge filtration, etc...), machinery and process for manufacturing (textile washing, paint manufacture, etc). The development of different cavitational reactors for liquid treatment in continuous flow is helping to introduce into industry the wide potential of the area of sonochemistry. Processes such as water and effluent treatment, crystallization, soil remediation, etc have been already implemented at semi-industrial and/or industrial stage. Other single advances in sectors like mining or energy have also to be mentioned. The objective of this paper is to review some recent developments in ultrasonic processing to show the present situation and the prospective progresses of high-power ultrasonics as an innovative technology in many industrial sectors.

Requirements and design structure for Surya Satellite-1

NASA Astrophysics Data System (ADS)

Steven, H.; Huzain, M. F.

2018-05-01

Currently, there are various references on the manufacture of nanosatellite specifications weighing 1KG - 10KG.The Surya Satellite-1 is the first nanosatellite made by universities in Indonesia. The Surya Satellite-1 team gets a launch offer from Japan Aerospace Exploration Agency (JAXA) and, all the nanosatellites manufacturer racers at ICD (Interface Control Document) obtained from JAXA. The formation of the Satellite-1 Surya framework is also based on the provisions of JAXA. The various specifications and requirements specified by the JAXA space agency consisting of specific specifications such as the mass of nanosatellite 1U (10cm x 10cm x 11.65cm) size of at least 0.13KG and a maximum of 1.33KG, with the determination of a gravity point not exceeding 2 cm from the nanosatellite geometry center point. In the case of preventing solar radiation in space, there is a requirement that the structure of satellite structures on hard black anodization should be more than 10 meters in the surface of the satellite structure. In terms of detail, the satellite structure is a black hard anodized aluminum after its manufacturing process derived from the MIL-A-8625 document, type 3.

Sustainable design and manufacturing of multifunctional polymer nanocomposite coatings: A multiscale systems approach

NASA Astrophysics Data System (ADS)

Xiao, Jie

Polymer nanocomposites have a great potential to be a dominant coating material in a wide range of applications in the automotive, aerospace, ship-making, construction, and pharmaceutical industries. However, how to realize design sustainability of this type of nanostructured materials and how to ensure the true optimality of the product quality and process performance in coating manufacturing remain as a mountaintop area. The major challenges arise from the intrinsic multiscale nature of the material-process-product system and the need to manipulate the high levels of complexity and uncertainty in design and manufacturing processes. This research centers on the development of a comprehensive multiscale computational methodology and a computer-aided tool set that can facilitate multifunctional nanocoating design and application from novel function envisioning and idea refinement, to knowledge discovery and design solution derivation, and further to performance testing in industrial applications and life cycle analysis. The principal idea is to achieve exceptional system performance through concurrent characterization and optimization of materials, product and associated manufacturing processes covering a wide range of length and time scales. Multiscale modeling and simulation techniques ranging from microscopic molecular modeling to classical continuum modeling are seamlessly coupled. The tight integration of different methods and theories at individual scales allows the prediction of macroscopic coating performance from the fundamental molecular behavior. Goal-oriented design is also pursued by integrating additional methods for bio-inspired dynamic optimization and computational task management that can be implemented in a hierarchical computing architecture. Furthermore, multiscale systems methodologies are developed to achieve the best possible material application towards sustainable manufacturing. Automotive coating manufacturing, that involves paint spay and curing, is specifically discussed in this dissertation. Nevertheless, the multiscale considerations for sustainable manufacturing, the novel concept of IPP control, and the new PPDE-based optimization method are applicable to other types of manufacturing, e.g., metal coating development through electroplating. It is demonstrated that the methodological development in this dissertation can greatly facilitate experimentalists in novel material invention and new knowledge discovery. At the same time, they can provide scientific guidance and reveal various new opportunities and effective strategies for sustainable manufacturing.

Laser and electron-beam powder-bed additive manufacturing of metallic implants: A review on processes, materials and designs.

PubMed

Sing, Swee Leong; An, Jia; Yeong, Wai Yee; Wiria, Florencia Edith

2016-03-01

Additive manufacturing (AM), also commonly known as 3D printing, allows the direct fabrication of functional parts with complex shapes from digital models. In this review, the current progress of two AM processes suitable for metallic orthopaedic implant applications, namely selective laser melting (SLM) and electron beam melting (EBM) are presented. Several critical design factors such as the need for data acquisition for patient-specific design, design dependent porosity for osteo-inductive implants, surface topology of the implants and design for reduction of stress-shielding in implants are discussed. Additive manufactured biomaterials such as 316L stainless steel, titanium-6aluminium-4vanadium (Ti6Al4V) and cobalt-chromium (CoCr) are highlighted. Limitations and future potential of such technologies are also explored. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Low work function materials for microminiature energy conversion and recovery applications

DOEpatents

Zavadil, Kevin R.; Ruffner, Judith A.; King, Donald B.

2003-05-13

Low work function materials are disclosed together with methods for their manufacture and integration with electrodes used in thermionic conversion applications (specifically microminiature thermionic conversion applications). The materials include a mixed oxide system and metal in a compositionally modulated structure comprised of localized discontinuous structures of material that are deposited using techniques suited to IC manufacture, such as rf sputtering or CVD. The structures, which can include layers are then heated to coalescence yielding a thin film that is both durable and capable of electron emission under thermionic conversion conditions used for microminiature thermionic converters. Using the principles of the invention, thin film electrodes (emitters and collectors) required for microconverter technology are manufactured using a single process deposition so as to allow for full fabrication integration consistent with batch processing, and tailoring of emission/collection properties. In the preferred embodiment, the individual layers include mixed BaSrCaO, scandium oxide and tungsten.

Development of the Internet-Based Customer-Oriented Ordering System Framework for Complicated Mechanical Product

NASA Astrophysics Data System (ADS)

Ong, Mingwei; Watanuki, Keiichi

Recently, as consumers gradually prefer buying products that reflect their own personality, there exist some consumers who wish to involve in the product design process. Parallel with the popularization of e-business, many manufacturers have utilized the Internet to promote their products, and some have even built websites that enable consumers to select their desirable product specifications. Nevertheless, this method has not been applied on complicated mechanical product due to the facts that complicated mechanical product has a large number of specifications that inter-relate among one another. In such a case, ordinary consumers who are lacking of design knowledge, are not capable of determining these specifications. In this paper, a prototype framework called Internet-based consumer-oriented product ordering system has been developed in which it enables ordinary consumers to have large freedom in determining complicated mechanical product specifications, and meanwhile ensures that the manufacturing of the determined product is feasible.

Extraterrestrial processing and manufacturing of large space systems, volume 2, chapters 7-14 and appendices

NASA Technical Reports Server (NTRS)

Miller, R. H.; Smith, D. B. S.

1979-01-01

Production and support equipment specifications are described for the space manufacturing facility (SMF). Defined production equipment includes electromagnetic pumps for liquid metal, metal alloying furnaces, die casters, electron beam welders and cutters, glass forming for structural elements, and rolling. A cost analysis is presented which includes the development, the aquisition of all SMF elements, initial operating cost, maintenance and logistics cost, cost of terrestrial materials, and transportation cost for each major element. Computer program listings and outputs are appended.

Cartilage Tissue Engineering with Silk Fibroin Scaffolds Fabricated by Indirect Additive Manufacturing Technology.

PubMed

Chen, Chih-Hao; Liu, Jolene Mei-Jun; Chua, Chee-Kai; Chou, Siaw-Meng; Shyu, Victor Bong-Hang; Chen, Jyh-Ping

2014-03-13

Advanced tissue engineering (TE) technology based on additive manufacturing (AM) can fabricate scaffolds with a three-dimensional (3D) environment suitable for cartilage regeneration. Specifically, AM technology may allow the incorporation of complex architectural features. The present study involves the fabrication of 3D TE scaffolds by an indirect AM approach using silk fibroin (SF). From scanning electron microscopic observations, the presence of micro-pores and interconnected channels within the scaffold could be verified, resulting in a TE scaffold with both micro- and macro-structural features. The intrinsic properties, such as the chemical structure and thermal characteristics of SF, were preserved after the indirect AM manufacturing process. In vitro cell culture within the SF scaffold using porcine articular chondrocytes showed a steady increase in cell numbers up to Day 14. The specific production (per cell basis) of the cartilage-specific extracellular matrix component (collagen Type II) was enhanced with culture time up to 12 weeks, indicating the re-differentiation of chondrocytes within the scaffold. Subcutaneous implantation of the scaffold-chondrocyte constructs in nude mice also confirmed the formation of ectopic cartilage by histological examination and immunostaining.

10 CFR 70.39 - Specific licenses for the manufacture or initial transfer of calibration or reference sources.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 2 2010-01-01 2010-01-01 false Specific licenses for the manufacture or initial transfer... manufacture or initial transfer of calibration or reference sources. (a) An application for a specific license to manufacture or initially transfer calibration or reference sources containing plutonium, for...

Solvent-free dry powder coating process for low-cost manufacturing of LiNi1/3Mn1/3Co1/3O2 cathodes in lithium-ion batteries

NASA Astrophysics Data System (ADS)

Al-Shroofy, Mohanad; Zhang, Qinglin; Xu, Jiagang; Chen, Tao; Kaur, Aman Preet; Cheng, Yang-Tse

2017-06-01

We report a solvent-free dry powder coating process for making LiNi1/3Mn1/3Co1/3O2 (NMC) positive electrodes in lithium-ion batteries. This process eliminates volatile organic compound emission and reduces thermal curing time from hours to minutes. A mixture of NMC, carbon black, and poly(vinylidene difluoride) was electrostatically sprayed onto an aluminum current collector, forming a uniformly distributed electrode with controllable thickness and porosity. Charge/discharge cycling of the dry-powder-coated electrodes in lithium-ion half cells yielded a discharge specific capacity of 155 mAh g-1 and capacity retention of 80% for more than 300 cycles when the electrodes were tested between 3.0 and 4.3 V at a rate of C/5. The long-term cycling performance and durability of dry-powder coated electrodes are similar to those made by the conventional wet slurry-based method. This solvent-free dry powder coating process is a potentially lower-cost, higher-throughput, and more environmentally friendly manufacturing process compared with the conventional wet slurry-based electrode manufacturing method.

Additive Manufacturing of Tooling for Refrigeration Cabinet Foaming Processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Post, Brian K; Nuttall, David; Cukier, Michael

The primary objective of this project was to leverage the Big Area Additive Manufacturing (BAAM) process and materials into a long term, quick change tooling concept to drastically reduce product lead and development timelines and costs. Current refrigeration foam molds are complicated to manufacture involving casting several aluminum parts in an approximate shape, machining components of the molds and post fitting and shimming of the parts in an articulated fixture. The total process timeline can take over 6 months. The foaming process is slower than required for production, therefore multiple fixtures, 10 to 27, are required per refrigerator model. Moldsmore » are particular to a specific product configuration making mixed model assembly challenging for sequencing, mold changes or auto changeover features. The initial goal was to create a tool leveraging the ORNL materials and additive process to build a tool in 4 to 6 weeks or less. A secondary goal was to create common fixture cores and provide lightweight fixture sections that could be revised in a very short time to increase equipment flexibility reduce lead times, lower the barriers to first production trials, and reduce tooling costs.« less

Active and passive surveillance of enoxaparin generics: a case study relevant to biosimilars.

PubMed

Grampp, Gustavo; Bonafede, Machaon; Felix, Thomas; Li, Edward; Malecki, Michael; Sprafka, J Michael

2015-03-01

This retrospective analysis assessed the capability of active and passive safety surveillance systems to track product-specific safety events in the USA for branded and generic enoxaparin, a complex injectable subject to immune-related and other adverse events (AEs). Analysis of heparin-induced thrombocytopenia (HIT) incidence was performed on benefit claims for commercial and Medicare supplemental-insured individuals newly treated with enoxaparin under pharmacy benefit (1 January 2009 - 30 June 2012). Additionally, spontaneous reports from the FDA AE Reporting System were reviewed to identify incidence and attribution of enoxaparin-related reports to specific manufacturers. Specific, dispensed products were identifiable from National Drug Codes only in pharmacy-benefit databases, permitting sensitive comparison of HIT incidence in nearly a third of patients treated with brand or generic enoxaparin. After originator medicine's loss of exclusivity, only 5% of spontaneous reports were processed by generic manufacturers; reports attributable to specific generics were approximately ninefold lower than expected based on market share. Claims data were useful for active surveillance of enoxaparin generics dispensed under pharmacy benefits but not for products administered under medical benefits. These findings suggest that the current spontaneous reporting system will not distinguish product-specific safety signals for products distributed by multiple manufacturers, including biosimilars.

The process defines the product: what really matters in biosimilar design and production?

PubMed Central

Jaquez, Orlando A.

2017-01-01

Abstract Biologic drugs are highly complex molecules produced by living cells through a multistep manufacturing process. The key characteristics of these molecules, known as critical quality attributes (CQAs), can vary based on post-translational modifications that occur in the cellular environment or during the manufacturing process. The extent of the variation in each of the CQAs must be characterized for the originator molecule and systematically matched as closely as possible by the biosimilar developer to ensure bio-similarity. The close matching of the originator fingerprint is the foundation of the biosimilarity exercise, as the analytical tools designed to measure differences at the molecular level are far more sensitive and specific than tools available to physicians during clinical trials. Biosimilar development, therefore, has a greater focus on preclinical attributes compared with the development of an original biological agent. As changes in CQAs can occur at different stages of the manufacturing process, even small modifications to the process can alter biosimilar attributes beyond the point of similarity and impact clinical effectiveness and safety. The manufacturer’s ability to provide consistent production and quality control will greatly influence the acceptance of biosimilars. To this end, preventing drift from the required specifications over time and avoiding the various implications brought by product shortage will enhance biosimilar integration into daily practice. As most prescribers are not familiar with this new drug development paradigm, educational programmes will be needed so that prescribers see biosimilars as fully equivalent, efficacious and safe medicines when compared with originator products. PMID:28903544

Design and development of a layer-based additive manufacturing process for the realization of metal parts of designed mesostructure

NASA Astrophysics Data System (ADS)

Williams, Christopher Bryant

Low-density cellular materials, metallic bodies with gaseous voids, are a unique class of materials that are characterized by their high strength, low mass, good energy absorption characteristics, and good thermal and acoustic insulation properties. In an effort to take advantage of this entire suite of positive mechanical traits, designers are tailoring the cellular mesostructure for multiple design objectives. Unfortunately, existing cellular material manufacturing technologies limit the design space as they are limited to certain part mesostructure, material type, and macrostructure. The opportunity that exists to improve the design of existing products, and the ability to reap the benefits of cellular materials in new applications is the driving force behind this research. As such, the primary research goal of this work is to design, embody, and analyze a manufacturing process that provides a designer the ability to specify the material type, material composition, void morphology, and mesostructure topology for any conceivable part geometry. The accomplishment of this goal is achieved in three phases of research: (1) Design---Following a systematic design process and a rigorous selection exercise, a layer-based additive manufacturing process is designed that is capable of meeting the unique requirements of fabricating cellular material geometry. Specifically, metal parts of designed mesostructure are fabricated via three-dimensional printing of metal oxide ceramic powder followed by post-processing in a reducing atmosphere. (2) Embodiment ---The primary research hypothesis is verified through the use of the designed manufacturing process chain to successfully realize metal parts of designed mesostructure. (3) Modeling & Evaluation ---The designed manufacturing process is modeled in this final research phase so as to increase understanding of experimental results and to establish a foundation for future analytical modeling research. In addition to an analysis of the physics of primitive creation and an investigation of failure modes during the layered fabrication of thin trusses, build time and cost models are presented in order to verify claims of the process's economic benefits. The main contribution of this research is the embodiment of a novel manner for realizing metal parts of designed mesostructure.

Stabilized thermally beneficiated low rank coal and method of manufacture

DOEpatents

Viall, A.J.; Richards, J.M.

1999-01-26

A process is described for reducing the spontaneous combustion tendencies of thermally beneficiated low rank coals employing heat, air or an oxygen containing gas followed by an optional moisture addition. Specific reaction conditions are supplied along with knowledge of equipment types that may be employed on a commercial scale to complete the process. 3 figs.

MANTECH Project Book, 1992

DTIC Science & Technology

1992-01-01

RUGATE FILTER PROCESS AND PRODUCTION ................ 111 MANUFACTURING SCIENCE FOR TITANIUM ALUMINIDE COMPOSITE ENGINE STRU CTURES...rejection and mission filters , anti-reflection coatings, and dichroic layers which can have demanding optical requirements. Rugate m coatings can be used to...SCIENCE RUGATE FILTER PROCESS AND PRODUCTION CONTRACT NUMBER: F33615-86-C-5059STATEMENT OF NEED Achieving the optical performance specifications for

Carbon black dispersion pre-plating technology for printed wire board manufacturing. Final technology evaluation report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Folsom, D.W.; Gavaskar, A.R.; Jones, J.A.

1993-10-01

The project compared chemical use, waste generation, cost, and product quality between electroless copper and carbon-black-based preplating technologies at the printed wire board (PWB) manufacturing facility of McCurdy Circuits in Orange, CA. The carbon-black based preplating technology evaluated is used as an alternative process for electroless copper (EC) plating of through-holes before electrolytic copper plating. The specific process used at McCurdy is the BlackHole (BH) technology process, which uses a dispersion of carbon black in an aqueous solution to provide a conductive surface for subsequent electrolytic copper plating. The carbon-black dispersion technology provided effective waste reduction and long-term cost savings.more » The economic analysis determined that the new process was cost efficient because chemical use was reduced and the process proved more efficient; the payback period was less than 4 yrs.« less

Cold pressure welding of aluminium-steel blanks: Manufacturing process and electrochemical surface preparation

NASA Astrophysics Data System (ADS)

Schmidt, Hans Christian; Homberg, Werner; Orive, Alejandro Gonzalez; Grundmeier, Guido; Hordych, Illia; Maier, Hans Jürgen

2018-05-01

In this study the manufacture of aluminium-steel blanks by cold pressure welding and their preparation for a welding process through electrochemical surface treatment are investigated and discussed. The cold pressure welding process was done with an incremental rolling tool that allows for the partial pressure welding of two blanks along a prepared path. The influence of the surface preparation by electrochemical deposition of bond promoting organosilane-based agents and roughening on a nano-scale is investigated and compared to conventional surface treatments. Coating the surfaces with a thin organosilane-based film incorporating specific functional groups should promote additional bonding between the mating oxide layers; its influence on the total weld strength is studied. Pressure welding requires suitable process strategies, and the current advances in the proposed incremental rolling process for the combination of mild steel and aluminium are presented.

Manufacturing Process Developments for Regeneratively-Cooled Channel Wall Rocket Nozzles

NASA Technical Reports Server (NTRS)

Gradl, Paul; Brandsmeier, Will

2016-01-01

Regeneratively cooled channel wall nozzles incorporate a series of integral coolant channels to contain the coolant to maintain adequate wall temperatures and expand hot gas providing engine thrust and specific impulse. NASA has been evaluating manufacturing techniques targeting large scale channel wall nozzles to support affordability of current and future liquid rocket engine nozzles and thrust chamber assemblies. The development of these large scale manufacturing techniques focus on the liner formation, channel slotting with advanced abrasive water-jet milling techniques and closeout of the coolant channels to replace or augment other cost reduction techniques being evaluated for nozzles. NASA is developing a series of channel closeout techniques including large scale additive manufacturing laser deposition and explosively bonded closeouts. A series of subscale nozzles were completed evaluating these processes. Fabrication of mechanical test and metallography samples, in addition to subscale hardware has focused on Inconel 625, 300 series stainless, aluminum alloys as well as other candidate materials. Evaluations of these techniques are demonstrating potential for significant cost reductions for large scale nozzles and chambers. Hot fire testing is planned using these techniques in the future.

Surface modification of biomaterials and biomedical devices using additive manufacturing.

PubMed

Bose, Susmita; Robertson, Samuel Ford; Bandyopadhyay, Amit

2018-01-15

The demand for synthetic biomaterials in medical devices, pharmaceutical products and, tissue replacement applications are growing steadily due to aging population worldwide. The use for patient matched devices is also increasing due to availability and integration of new technologies. Applications of additive manufacturing (AM) or 3D printing (3DP) in biomaterials have also increased significantly over the past decade towards traditional as well as innovative next generation Class I, II and III devices. In this review, we have focused our attention towards the use of AM in surface modified biomaterials to enhance their in vitro and in vivo performances. Specifically, we have discussed the use of AM to deliberately modify the surfaces of different classes of biomaterials with spatial specificity in a single manufacturing process as well as commented on the future outlook towards surface modification using AM. It is widely understood that the success of implanted medical devices depends largely on favorable material-tissue interactions. Additive manufacturing has gained traction as a viable and unique approach to engineered biomaterials, for both bulk and surface properties that improve implant outcomes. This review explores how additive manufacturing techniques have been and can be used to augment the surfaces of biomedical devices for direct clinical applications. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Risks and reliability of manufacturing processes as related to composite materials for spacecraft structures

NASA Technical Reports Server (NTRS)

Bao, Han P.

1995-01-01

Fabricating primary aircraft and spacecraft structures using advanced composite materials entail both benefits and risks. The benefits come from much improved strength-to-weight ratios and stiffness-to-weight ratios, potential for less part count, ability to tailor properties, chemical and solvent resistance, and superior thermal properties. On the other hand, the risks involved include high material costs, lack of processing experience, expensive labor, poor reproducibility, high toxicity for some composites, and a variety of space induced risks. The purpose of this project is to generate a manufacturing database for a selected number of materials with potential for space applications, and to rely on this database to develop quantitative approaches to screen candidate materials and processes for space applications on the basis of their manufacturing risks including costs. So far, the following materials have been included in the database: epoxies, polycyanates, bismalemides, PMR-15, polyphenylene sulfides, polyetherimides, polyetheretherketone, and aluminum lithium. The first four materials are thermoset composites; the next three are thermoplastic composites, and the last one is is a metal. The emphasis of this database is on factors affecting manufacturing such as cost of raw material, handling aspects which include working life and shelf life of resins, process temperature, chemical/solvent resistance, moisture resistance, damage tolerance, toxicity, outgassing, thermal cycling, and void content, nature or type of process, associate tooling, and in-process quality assurance. Based on industry experience and published literature, a relative ranking was established for each of the factors affecting manufacturing as listed above. Potential applications of this database include the determination of a delta cost factor for specific structures with a given process plan and a general methodology to screen materials and processes for incorporation into the current conceptual design optimization of future spacecrafts as being coordinated by the Vehicle Analysis Branch where this research is being conducted.

A specific nanomanufacturing challenge

NASA Astrophysics Data System (ADS)

Kelly, M. J.; Dean, M. C.

2016-03-01

For a science to become a technology, a certain level of control has to have been established over the way items are fabricated for manufacture and use. Here we first consider the challenge of making and using a LEGO® brick scaled down by a factor of 10 n for n = 0-6 in each spatial dimension, i.e. from millimetres to nanometres. We consider both the manufacture and the subsequent properties of the nanobricks that pertain to their use in constructing and dismantling structures. As n increases, the ability to use fails first, to manufacture fails second and to fabricate fails last. Applied to the vast literature in nanoscience, this process emphasises the unmanufacturability of most nanoscale artefacts.

Diverse task scheduling for individualized requirements in cloud manufacturing

NASA Astrophysics Data System (ADS)

Zhou, Longfei; Zhang, Lin; Zhao, Chun; Laili, Yuanjun; Xu, Lida

2018-03-01

Cloud manufacturing (CMfg) has emerged as a new manufacturing paradigm that provides ubiquitous, on-demand manufacturing services to customers through network and CMfg platforms. In CMfg system, task scheduling as an important means of finding suitable services for specific manufacturing tasks plays a key role in enhancing the system performance. Customers' requirements in CMfg are highly individualized, which leads to diverse manufacturing tasks in terms of execution flows and users' preferences. We focus on diverse manufacturing tasks and aim to address their scheduling issue in CMfg. First of all, a mathematical model of task scheduling is built based on analysis of the scheduling process in CMfg. To solve this scheduling problem, we propose a scheduling method aiming for diverse tasks, which enables each service demander to obtain desired manufacturing services. The candidate service sets are generated according to subtask directed graphs. An improved genetic algorithm is applied to searching for optimal task scheduling solutions. The effectiveness of the scheduling method proposed is verified by a case study with individualized customers' requirements. The results indicate that the proposed task scheduling method is able to achieve better performance than some usual algorithms such as simulated annealing and pattern search.

3D Printed Surgical Instruments: The Design and Fabrication Process.

PubMed

George, Mitchell; Aroom, Kevin R; Hawes, Harvey G; Gill, Brijesh S; Love, Joseph

2017-01-01

3D printing is an additive manufacturing process allowing the creation of solid objects directly from a digital file. We believe recent advances in additive manufacturing may be applicable to surgical instrument design. This study investigates the feasibility, design and fabrication process of usable 3D printed surgical instruments. The computer-aided design package SolidWorks (Dassault Systemes SolidWorks Corp., Waltham MA) was used to design a surgical set including hemostats, needle driver, scalpel handle, retractors and forceps. These designs were then printed on a selective laser sintering (SLS) Sinterstation HiQ (3D Systems, Rock Hill SC) using DuraForm EX plastic. The final printed products were evaluated by practicing general surgeons for ergonomic functionality and performance, this included simulated surgery and inguinal hernia repairs on human cadavers. Improvements were identified and addressed by adjusting design and build metrics. Repeated manufacturing processes and redesigns led to the creation of multiple functional and fully reproducible surgical sets utilizing the user feedback of surgeons. Iterative cycles including design, production and testing took an average of 3 days. Each surgical set was built using the SLS Sinterstation HiQ with an average build time of 6 h per set. Functional 3D printed surgical instruments are feasible. Advantages compared to traditional manufacturing methods include no increase in cost for increased complexity, accelerated design to production times and surgeon specific modifications.

Aerospace Environmental Technology Conference

NASA Technical Reports Server (NTRS)

Whitaker, A. F. (Editor)

1995-01-01

The mandated elimination of CFC's, Halons, TCA, and other ozone depleting chemicals and specific hazardous materials has required changes and new developments in aerospace materials and processes. The aerospace industry has been involved for several years in providing product substitutions, redesigning entire production processes, and developing new materials that minimize or eliminate damage to the environment. These activities emphasize replacement cleaning solvents and their application verifications, compliant coatings including corrosion protection systems, and removal techniques, chemical propulsion effects on the environment, and the initiation of modifications to relevant processing and manufacturing specifications and standards. The Executive Summary of this Conference is published as NASA CP-3297.

Monolayer boron-aluminum compacted sheet material

NASA Technical Reports Server (NTRS)

Sumner, E. V.

1973-01-01

The manufacturing techniques, basic materials used, and equipment required to produce monolayer boron-aluminum composites are described. Tentative materials and process specifications are included. Improvements in bonding and filament spacing obtained through use of brazing powder in the fugitive binder are discussed.

Design and specification of a centralized manufacturing data management and scheduling system

NASA Technical Reports Server (NTRS)

Farrington, Phillip A.

1993-01-01

As was revealed in a previous study, the Materials and Processes Laboratory's Productivity Enhancement Complex (PEC) has a number of automated production areas/cells that are not effectively integrated, limiting the ability of users to readily share data. The recent decision to utilize the PEC for the fabrication of flight hardware has focused new attention on the problem and brought to light the need for an integrated data management and scheduling system. This report addresses this need by developing preliminary designs specifications for a centralized manufacturing data management and scheduling system for managing flight hardware fabrication in the PEC. This prototype system will be developed under the auspices of the Integrated Engineering Environment (IEE) Oversight team and the IEE Committee. At their recommendation the system specifications were based on the fabrication requirements of the AXAF-S Optical Bench.

Towards a service bus for distributed manufacturing

NASA Astrophysics Data System (ADS)

Delgado-Gomes, Vasco; Oliveira-Lima, José A.; Martins, João F.; Jardim-Gonçalves, Ricardo

2013-10-01

The electronic exchange of data between industrial equipment, manufacturing and information systems of companies is becoming increasingly important with the current trend of reducing products' life cycle, wide range of diversified products, and the need to answer the specific needs of each consumer. In this context, quality, time, costs involved in integrating information over the company's internal processes, and in the interaction of these processes with their customers, suppliers and other business partners are in many sectors, far beyond what the current technology and communications solutions enable. This paper presents a communication infrastructure to integrate several companies from different sectors of the supply chain, to exchange their heterogeneous information using a data model which is composed by different standards.

Commercial-scale biotherapeutics manufacturing facility for plant-made pharmaceuticals.

PubMed

Holtz, Barry R; Berquist, Brian R; Bennett, Lindsay D; Kommineni, Vally J M; Munigunti, Ranjith K; White, Earl L; Wilkerson, Don C; Wong, Kah-Yat I; Ly, Lan H; Marcel, Sylvain

2015-10-01

Rapid, large-scale manufacture of medical countermeasures can be uniquely met by the plant-made-pharmaceutical platform technology. As a participant in the Defense Advanced Research Projects Agency (DARPA) Blue Angel project, the Caliber Biotherapeutics facility was designed, constructed, commissioned and released a therapeutic target (H1N1 influenza subunit vaccine) in <18 months from groundbreaking. As of 2015, this facility was one of the world's largest plant-based manufacturing facilities, with the capacity to process over 3500 kg of plant biomass per week in an automated multilevel growing environment using proprietary LED lighting. The facility can commission additional plant grow rooms that are already built to double this capacity. In addition to the commercial-scale manufacturing facility, a pilot production facility was designed based on the large-scale manufacturing specifications as a way to integrate product development and technology transfer. The primary research, development and manufacturing system employs vacuum-infiltrated Nicotiana benthamiana plants grown in a fully contained, hydroponic system for transient expression of recombinant proteins. This expression platform has been linked to a downstream process system, analytical characterization, and assessment of biological activity. This integrated approach has demonstrated rapid, high-quality production of therapeutic monoclonal antibody targets, including a panel of rituximab biosimilar/biobetter molecules and antiviral antibodies against influenza and dengue fever. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Splendidly blended: a machine learning set up for CDU control

NASA Astrophysics Data System (ADS)

Utzny, Clemens

2017-06-01

As the concepts of machine learning and artificial intelligence continue to grow in importance in the context of internet related applications it is still in its infancy when it comes to process control within the semiconductor industry. Especially the branch of mask manufacturing presents a challenge to the concepts of machine learning since the business process intrinsically induces pronounced product variability on the background of small plate numbers. In this paper we present the architectural set up of a machine learning algorithm which successfully deals with the demands and pitfalls of mask manufacturing. A detailed motivation of this basic set up followed by an analysis of its statistical properties is given. The machine learning set up for mask manufacturing involves two learning steps: an initial step which identifies and classifies the basic global CD patterns of a process. These results form the basis for the extraction of an optimized training set via balanced sampling. A second learning step uses this training set to obtain the local as well as global CD relationships induced by the manufacturing process. Using two production motivated examples we show how this approach is flexible and powerful enough to deal with the exacting demands of mask manufacturing. In one example we show how dedicated covariates can be used in conjunction with increased spatial resolution of the CD map model in order to deal with pathological CD effects at the mask boundary. The other example shows how the model set up enables strategies for dealing tool specific CD signature differences. In this case the balanced sampling enables a process control scheme which allows usage of the full tool park within the specified tight tolerance budget. Overall, this paper shows that the current rapid developments off the machine learning algorithms can be successfully used within the context of semiconductor manufacturing.

Topical otic drugs in a multi-purpose manufacturing facility: a guide on determination and application of permitted daily exposure (PDE).

PubMed

Wiesner, Lisa; Prause, Maarten; Lovsin Barle, Ester

2018-03-01

Due to newly introduced EU GMP (Good Manufacturing Practice) guideline for Medicinal Products for Human and Veterinary use, product specific permitted daily exposure (PDE) for toxicological evaluation in multi-purpose facilities are required within a documented process for risk assessment. European Medicines Agency (EMA) guidance on setting PDE limits so far focused on systemic administration routes such as intravenous (IV), oral or inhalation. This article provides guidance on setting PDE values for risk management purposes in multi-purpose facilities for active pharmaceutical ingredients (APIs) applied as topical otic drugs to the outer ear canal. The therewith determined PDE otic, is used for the calculation of maximum safe carry-over (MSC) in manufacturing scenarios where a topical otic product is manufactured followed by another topical otic product.

Additive Manufacturing Technology for Biomedical Components: A review

NASA Astrophysics Data System (ADS)

Aimi Zaharin, Haizum; Rani, Ahmad Majdi Abdul; Lenggo Ginta, Turnad; Azam, Farooq I.

2018-03-01

Over the last decades, additive manufacturing has shown potential application in ranging fields. No longer a prototyping technology, it is now being utilised as a manufacturing technology for giant industries such as the automotive, aircraft and recently in the medical industry. It is a very successful method that provides health-care solution in biomedical sectors by producing patient-specific prosthetics, improve tissues engineering and facilitate pre-operating session. This paper thus presents a brief overview of the most commercially important additive manufacturing technologies, which is currently available for fabricating biomedical components such as Stereolithography (SLA), Selective Laser Sintering (SLS), Selective Laser Melting (SLM), Fused Deposition Modelling (FDM) and Electron Beam Melting (EBM). It introduces the basic principles of the main process, highlights some of the beneficial applications in medical industry and the current limitation of applied technology.

Universal pooled plasma (Uniplas(®)) does not induce complement-mediated hemolysis of human red blood cells in vitro.

PubMed

Heger, Andrea; Brandstätter, Hubert; Prager, Bettina; Brainovic, Janja; Cortes, Rhoda; Römisch, Jürgen

2015-02-01

Pooling of plasma of different blood groups before large scale manufacturing of Uniplas(®) results in the formation of low levels of soluble immune complexes (CIC). The aim of this study was to investigate the level and removal of CIC during Uniplas(®) manufacturing. In addition, an in vitro hemolysis assay should be developed and investigate if Uniplas(®) does induce complement-mediated hemolysis of human red blood cells (RBC). In-process samples from Uniplas(®) (universal plasma) and Octaplas(LG)(®) (blood group specific plasma) routine manufacturing batches were tested on CIC using commercially available ELISA test kits. In addition, CIC was produced by admixing heat-aggregated immunoglobulins or monoclonal anti-A/anti-B antibodies to plasma and removal of CIC was followed in studies of the Uniplas(®) manufacturing process under down-scale conditions. The extent of RBC lysis was investigated in plasma samples using the in-house hemolysis assay. Levels of CIC in Uniplas(®) are within the normal ranges for plasma and comparable to that found in Octaplas(LG)(®). Down-scale experiments showed that both IgG/IgM-CIC levels are significantly removed on average by 40-50% during Uniplas(®) manufacturing. Uniplas(®) does not induce hemolysis of RBCs in vitro. Hemolysis occurs only after spiking with high titers of anti-A/anti-B antibodies and depends on the antibody specificity (i.e. titer) in the plasma sample. The results of this study confirm the safety of Uniplas(®) regarding transfusion to patients of all ABO blood groups. Copyright © 2013 Elsevier Ltd. All rights reserved.

Microstructures and Grain Refinement of Additive-Manufactured Ti- xW Alloys

NASA Astrophysics Data System (ADS)

Mendoza, Michael Y.; Samimi, Peyman; Brice, David A.; Martin, Brian W.; Rolchigo, Matt R.; LeSar, Richard; Collins, Peter C.

2017-07-01

It is necessary to better understand the composition-processing-microstructure relationships that exist for materials produced by additive manufacturing. To this end, Laser Engineered Net Shaping (LENS™), a type of additive manufacturing, was used to produce a compositionally graded titanium binary model alloy system (Ti- xW specimen (0 ≤ x ≤ 30 wt pct), so that relationships could be made between composition, processing, and the prior beta grain size. Importantly, the thermophysical properties of the Ti- xW, specifically its supercooling parameter ( P) and growth restriction factor ( Q), are such that grain refinement is expected and was observed. The systematic, combinatorial study of this binary system provides an opportunity to assess the mechanisms by which grain refinement occurs in Ti-based alloys in general, and for additive manufacturing in particular. The operating mechanisms that govern the relationship between composition and grain size are interpreted using a model originally developed for aluminum and magnesium alloys and subsequently applied for titanium alloys. The prior beta grain factor observed and the interpretations of their correlations indicate that tungsten is a good grain refiner and such models are valid to explain the grain-refinement process. By extension, other binary elements or higher order alloy systems with similar thermophysical properties should exhibit similar grain refinement.

15 CFR 400.33 - Restrictions on manufacturing and processing activity.

Code of Federal Regulations, 2010 CFR

2010-01-01

...-TRADE ZONES BOARD Manufacturing and Processing Activity-Reviews § 400.33 Restrictions on manufacturing and processing activity. (a) In general. In approving manufacturing or processing activity for a zone... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Restrictions on manufacturing and...

21 CFR 1005.25 - Service of process on manufacturers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Service of process on manufacturers. 1005.25....25 Service of process on manufacturers. (a) Every manufacturer of electronic products, prior to... United States as the manufacturer's agent upon whom service of all processes, notices, orders, decisions...

An Interoperability Framework and Capability Profiling for Manufacturing Software

NASA Astrophysics Data System (ADS)

Matsuda, M.; Arai, E.; Nakano, N.; Wakai, H.; Takeda, H.; Takata, M.; Sasaki, H.

ISO/TC184/SC5/WG4 is working on ISO16100: Manufacturing software capability profiling for interoperability. This paper reports on a manufacturing software interoperability framework and a capability profiling methodology which were proposed and developed through this international standardization activity. Within the context of manufacturing application, a manufacturing software unit is considered to be capable of performing a specific set of function defined by a manufacturing software system architecture. A manufacturing software interoperability framework consists of a set of elements and rules for describing the capability of software units to support the requirements of a manufacturing application. The capability profiling methodology makes use of the domain-specific attributes and methods associated with each specific software unit to describe capability profiles in terms of unit name, manufacturing functions, and other needed class properties. In this methodology, manufacturing software requirements are expressed in terns of software unit capability profiles.

Comparative evaluation of microbial diversity and metabolite profiles in doenjang, a fermented soybean paste, during the two different industrial manufacturing processes.

PubMed

Lee, Sunmin; Lee, Sarah; Singh, Digar; Oh, Ji Young; Jeon, Eun Jung; Ryu, Hyung SeoK; Lee, Dong Wan; Kim, Beom Seok; Lee, Choong Hwan

2017-04-15

Two different doenjang manufacturing processes, the industrial process (IP) and the modified industrial process (mIP) with specific microbial assortments, were subjected to metabolite profiling using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). The multivariate analyses indicated that both primary and secondary metabolites exhibited distinct patterns according to the fermentation processes (IP and mIP). Microbial community analysis for doenjang using denaturing gradient gel electrophoresis (DGGE), exhibited that both bacteria and fungi contributed proportionally for each step in the process viz., soybean, steaming, drying, meju fermentation, cooling, brining, and aging. Further, correlation analysis indicated that Aspergillus population was linked to sugar metabolism, Bacillus spp. with that of fatty acids, whereas Tetragenococcus and Zygosaccharomyces were found associated with amino acids. These results suggest that the components and quality of doenjang are critically influenced by the microbial assortments in each process. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of Company Size on Manufacturing Improvement Practices: An empirical study

NASA Astrophysics Data System (ADS)

Syan, C. S.; Ramoutar, K.

2014-07-01

There is a constant search for ways to achieve a competitive advantage through new manufacturing techniques. Best performing manufacturing companies tend to use world-class manufacturing (WCM) practices. Although the last few years have witnessed phenomenal growth in the use of WCM techniques, their effectiveness is not well understood specifically in the context of less developed countries. This paper presents an empirical study to investigate the impact of company size on improving manufacturing performance in manufacturing organizations based in Trinidad and Tobago (T&T). Empirical data were collected via a questionnaire survey which was send to 218 manufacturing firms in T&T. Five different company sizes and seven different industry sectors were studied. The analysis of survey data was performed with the aid of Statistical Package for Social Sciences (SPSS) software. The study signified facilitating and impeding factors towards improving manufacturing performance. Their relative impact/importance is dependent on varying company size and industry sectors. Findings indicate that T&T manufacturers are still practicing traditional approaches, when compared with world class manufacturers. In the majority of organizations, these practices were not 100% implemented even though they started the implementation process more than 5 years ago. The findings provided some insights in formulating more optimal operational strategies, and later develop action plans towards more effective implementation of WCM in T&T manufacturers.

Quality Risk Management: Putting GMP Controls First.

PubMed

O'Donnell, Kevin; Greene, Anne; Zwitkovits, Michael; Calnan, Nuala

2012-01-01

This paper presents a practical way in which current approaches to quality risk management (QRM) may be improved, such that they better support qualification, validation programs, and change control proposals at manufacturing sites. The paper is focused on the treatment of good manufacturing practice (GMP) controls during QRM exercises. It specifically addresses why it is important to evaluate and classify such controls in terms of how they affect the severity, probability of occurrence, and detection ratings that may be assigned to potential failure modes or negative events. It also presents a QRM process that is designed to directly link the outputs of risk assessments and risk control activities with qualification and validation protocols in the GMP environment. This paper concerns the need for improvement in the use of risk-based principles and tools when working to ensure that the manufacturing processes used to produce medicines, and their related equipment, are appropriate. Manufacturing processes need to be validated (or proven) to demonstrate that they can produce a medicine of the required quality. The items of equipment used in such processes need to be qualified, in order to prove that they are fit for their intended use. Quality risk management (QRM) tools can be used to support such qualification and validation activities, but their use should be science-based and subject to as little subjectivity and uncertainty as possible. When changes are proposed to manufacturing processes, equipment, or related activities, they also need careful evaluation to ensure that any risks present are managed effectively. This paper presents a practical approach to how QRM may be improved so that it better supports qualification, validation programs, and change control proposals in a more scientific way. This improved approach is based on the treatment of what are called good manufacturing process (GMP) controls during those QRM exercises. A GMP control can be considered to be any control that is put in place to assure product quality and regulatory compliance. This improved approach is also based on how the detectability of risks is assessed. This is important because when producing medicines, it is not always good practice to place a high reliance upon detection-type controls in the absence of an adequate level of assurance in the manufacturing process that leads to the finished medicine.

Multiphysics modeling of selective laser sintering/melting

NASA Astrophysics Data System (ADS)

Ganeriwala, Rishi Kumar

A significant percentage of total global employment is due to the manufacturing industry. However, manufacturing also accounts for nearly 20% of total energy usage in the United States according to the EIA. In fact, manufacturing accounted for 90% of industrial energy consumption and 84% of industry carbon dioxide emissions in 2002. Clearly, advances in manufacturing technology and efficiency are necessary to curb emissions and help society as a whole. Additive manufacturing (AM) refers to a relatively recent group of manufacturing technologies whereby one can 3D print parts, which has the potential to significantly reduce waste, reconfigure the supply chain, and generally disrupt the whole manufacturing industry. Selective laser sintering/melting (SLS/SLM) is one type of AM technology with the distinct advantage of being able to 3D print metals and rapidly produce net shape parts with complicated geometries. In SLS/SLM parts are built up layer-by-layer out of powder particles, which are selectively sintered/melted via a laser. However, in order to produce defect-free parts of sufficient strength, the process parameters (laser power, scan speed, layer thickness, powder size, etc.) must be carefully optimized. Obviously, these process parameters will vary depending on material, part geometry, and desired final part characteristics. Running experiments to optimize these parameters is costly, energy intensive, and extremely material specific. Thus a computational model of this process would be highly valuable. In this work a three dimensional, reduced order, coupled discrete element - finite difference model is presented for simulating the deposition and subsequent laser heating of a layer of powder particles sitting on top of a substrate. Validation is provided and parameter studies are conducted showing the ability of this model to help determine appropriate process parameters and an optimal powder size distribution for a given material. Next, thermal stresses upon cooling are calculated using the finite difference method. Different case studies are performed and general trends can be seen. This work concludes by discussing future extensions of this model and the need for a multi-scale approach to achieve comprehensive part-level models of the SLS/SLM process.

A Decade of Friction Stir Welding R and D at NASA's Marshall Space Flight Center and a Glance into the Future

NASA Technical Reports Server (NTRS)

Ding, Jeff; Carter, Bob; Lawless, Kirby; Nunes, Arthur; Russell, Carolyn; Suites, Michael; Schneider, Judy

2006-01-01

Welding at NASA's Marshall Space Flight Center (MSFC), Huntsville, Alabama, has taken a new direction through the last 10 years. Fusion welding processes, namely variable polarity plasma arc (VPPA) and tungsten inert gas (TIG) were once the corner stone of welding development in the Space Flight Center's welding laboratories, located in the part of MSFC know as National Center for Advanced Manufacturing (NCM). Developed specifically to support the Shuttle Program's External Tank and later International Space Station manufacturing programs, was viewed as the paragon of welding processes for joining aluminum alloys. Much has changed since 1994, however, when NASA's Jeff Ding brought the FSW process to the NASA agency. Although, at that time, FSW was little more than a "lab curiosity", NASA researchers started investigating where the FSW process would best fit NASA manufacturing programs. A laboratory FSW system was procured and the first welds were made in fall of 1995. The small initial investment NASA made into the first FSW system has certainly paid off for the NASA agency in terms of cost savings, hardware quality and notoriety. FSW is now a part of Shuttle External Tank (ET) production and the preferred weld process for the manufacturing of components for the new Crew Launch Vehicle (CLV) and Heavy Lift Launch Vehicle (HLLV) that will take this country back to the moon. It is one of the solid state welding processes being considered for on-orbit space welding and repair, and is of considerable interest for Department of Defense @OD) manufacturing programs. MSFC involvement in these and other programs makes NASA a driving force in this country's development of FSW and other solid state welding technologies. Now, a decade later, almost the entire on-going welding R&D at MSFC now focuses on FSW and other more advanced solid state welding processes.

Quality management of manufacturing process based on manufacturing execution system

NASA Astrophysics Data System (ADS)

Zhang, Jian; Jiang, Yang; Jiang, Weizhuo

2017-04-01

Quality control elements in manufacturing process are elaborated. And the approach of quality management of manufacturing process based on manufacturing execution system (MES) is discussed. The functions of MES for a microcircuit production line are introduced conclusively.

Control of Technology Transfer at JPL

NASA Technical Reports Server (NTRS)

Oliver, Ronald

2006-01-01

Controlled Technology: 1) Design: preliminary or critical design data, schematics, technical flow charts, SNV code/diagnostics, logic flow diagrams, wirelist, ICDs, detailed specifications or requirements. 2) Development: constraints, computations, configurations, technical analyses, acceptance criteria, anomaly resolution, detailed test plans, detailed technical proposals. 3) Production: process or how-to: assemble, operated, repair, maintain, modify. 4) Manufacturing: technical instructions, specific parts, specific materials, specific qualities, specific processes, specific flow. 5) Operations: how-to operate, contingency or standard operating plans, Ops handbooks. 6) Repair: repair instructions, troubleshooting schemes, detailed schematics. 7) Test: specific procedures, data, analysis, detailed test plan and retest plans, detailed anomaly resolutions, detailed failure causes and corrective actions, troubleshooting, trended test data, flight readiness data. 8) Maintenance: maintenance schedules and plans, methods for regular upkeep, overhaul instructions. 9) Modification: modification instructions, upgrades kit parts, including software

Preparing clinical grade Ag-specific T cells for adoptive immunotherapy trials

PubMed Central

DiGiusto, DL; Cooper, LJN

2007-01-01

The production of clinical-grade T cells for adoptive immunotherapy has evolved from the ex vivo numerical expansion of tumor-infiltrating lymphocytes to sophisticated bioengineering processes often requiring cell selection, genetic modification and other extensive tissue culture manipulations, to produce desired cells with improved therapeutic potential. Advancements in understanding the biology of lymphocyte signaling, activation, homing and sustained in vivo proliferative potential have redefined the strategies used to produce T cells suitable for clinical investigation. When combined with new technical methods in cell processing and culturing, the therapeutic potential of T cells manufactured in academic centers has improved dramatically. Paralleling these technical achievements in cell manufacturing is the development of broadly applied regulatory standards that define the requirements for the clinical implementation of cell products with ever-increasing complexity. In concert with academic facilities operating in compliance with current good manufacturing practice, the prescribing physician can now infuse T cells with a highly selected or endowed phenotype that has been uniformly manufactured according to standard operating procedures and that meets federal guidelines for quality of investigational cell products. In this review we address salient issues related to the technical, immunologic, practical and regulatory aspects of manufacturing these advanced T-cell products for clinical use. PMID:17943498

The Impact of Granule Density on Tabletting and Pharmaceutical Product Performance.

PubMed

van den Ban, Sander; Goodwin, Daniel J

2017-05-01

The impact of granule densification in high-shear wet granulation on tabletting and product performance was investigated, at pharmaceutical production scale. Product performance criteria need to be balanced with the need to deliver manufacturability criteria to assure robust industrial scale tablet manufacturing processes. A Quality by Design approach was used to determine in-process control specifications for tabletting, propose a design space for disintegration and dissolution, and to understand the permitted operating limits and required controls for an industrial tabletting process. Granules of varying density (filling density) were made by varying water amount added, spray rate, and wet massing time in a design of experiment (DoE) approach. Granules were compressed into tablets to a range of thicknesses to obtain tablets of varying breaking force. Disintegration and dissolution performance was evaluated for the tablets made. The impact of granule filling density on tabletting was rationalised with compressibility, tabletability and compactibility. Tabletting and product performance criteria provided competing requirements for porosity. An increase in granule filling density impacted tabletability and compactability and limited the ability to achieve tablets of adequate mechanical strength. An increase in tablet solid fraction (decreased porosity) impacted disintegration and dissolution. An attribute-based design space for disintegration and dissolution was specified to achieve both product performance and manufacturability. The method of granulation and resulting granule filling density is a key design consideration to achieve both product performance and manufacturability required for modern industrial scale pharmaceutical product manufacture and distribution.

Development and demonstration of manufacturing processes for fabricating graphite/LARC-160 polyimide structural elements, part 4, paragraph B

NASA Technical Reports Server (NTRS)

1980-01-01

A quality assurance program was developed which included specifications for celion/LARC-160 polyimide materials and quality control of materials and processes. The effects of monomers and/or polymer variables and prepeg variables on the processibility of celion/LARC prepeg were included. Processes for fabricating laminates, honeycomb core panels, and chopped fiber moldings were developed. Specimens and conduct tests were fabricated to qualify the processes for fabrication of demonstration components.

Transition process from emerging NDT technology to production inspection application

NASA Astrophysics Data System (ADS)

Jappe, William; Wood, Nancy; Johnson, Maurice

1995-07-01

The successful application of emerging NDT technologies for specific aging aircraft inspections requires an integration of efforts between aircraft operators, airframe manufacturers, NDT equipment designers, and government regulators. This paper describes the development process that was followed to establish an alternate inspection technique for a DC-10 crown skin butt joint inspection. Initial investigation, intermediate development, and final evaluations are discussed.

40 CFR 721.825 - Certain aromatic ether diamines.

Code of Federal Regulations, 2011 CFR

2011-07-01

... ester, compound with 4,4′-[[1,1′-biphenyl]-2,5-diylbis(oxy)]bis[benzenamine] (1:1), polymer with 4,4...: Manufacture, import, or processing in a quantity of 100,000 pounds per year, or greater, for any use. (3) The..., import, or processing in a quantity of 225,000 pounds per year, or greater, for any use. (b) Specific...

40 CFR 180.108 - Acephate; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

... establishments, including food service, manufacturing and processing establishments, such as restaurants... avoid atomization or splashing of the spray. Contamination of food or food-contact surfaces shall be... PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.108...

40 CFR 180.435 - Deltamethrin; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

... in food handling establishments, including food service, manufacturing and processing establishments.... Contamination of food/feed or food/feed contact surfaces shall be avoided. (B) To assure safe use of the...) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances...

40 CFR 180.422 - Tralomethrin; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

...-handling establishments, including food service, manufacturing, and processing establishments, such as... shall be limited to a maximum of 0.06 percent active ingredient. Contamination of food and food-contact...) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances...

Draw forming of scale shuttle external tank dome gores

NASA Technical Reports Server (NTRS)

Garfield, G.

1974-01-01

The process for manufacturing external tank dome gores is discussed. The test fixture and test procedure are described. The characteristics of the draw forming die are analyzed. The specific subjects included are: (1) forming, (2) trimming, (3) cleaning, and (4) heat treatment.

Development and production of good manufacturing practice grade human embryonic stem cell lines as source material for clinical application.

PubMed

De Sousa, P A; Downie, J M; Tye, B J; Bruce, K; Dand, P; Dhanjal, S; Serhal, P; Harper, J; Turner, M; Bateman, M

2016-09-01

From 2006 to 2011, Roslin Cells Ltd derived 17 human embryonic stem cells (hESC) while developing (RCM1, RC-2 to -8, -10) and implementing (RC-9, -11 to -17) quality assured standards of operation in a facility operating in compliance with European Union (EU) directives and United Kingdom (UK) licensure for procurement, processing and storage of human cells as source material for clinical application, and targeted to comply with an EU Good Manufacturing Practice specification. Here we describe the evolution and specification of the facility, its operation and outputs, complementing hESC resource details communicated in Stem Cell Research Lab Resources. Copyright © 2016. Published by Elsevier B.V.

A practical approach for exploration and modeling of the design space of a bacterial vaccine cultivation process.

PubMed

Streefland, M; Van Herpen, P F G; Van de Waterbeemd, B; Van der Pol, L A; Beuvery, E C; Tramper, J; Martens, D E; Toft, M

2009-10-15

A licensed pharmaceutical process is required to be executed within the validated ranges throughout the lifetime of product manufacturing. Changes to the process, especially for processes involving biological products, usually require the manufacturer to demonstrate that the safety and efficacy of the product remains unchanged by new or additional clinical testing. Recent changes in the regulations for pharmaceutical processing allow broader ranges of process settings to be submitted for regulatory approval, the so-called process design space, which means that a manufacturer can optimize his process within the submitted ranges after the product has entered the market, which allows flexible processes. In this article, the applicability of this concept of the process design space is investigated for the cultivation process step for a vaccine against whooping cough disease. An experimental design (DoE) is applied to investigate the ranges of critical process parameters that still result in a product that meets specifications. The on-line process data, including near infrared spectroscopy, are used to build a descriptive model of the processes used in the experimental design. Finally, the data of all processes are integrated in a multivariate batch monitoring model that represents the investigated process design space. This article demonstrates how the general principles of PAT and process design space can be applied for an undefined biological product such as a whole cell vaccine. The approach chosen for model development described here, allows on line monitoring and control of cultivation batches in order to assure in real time that a process is running within the process design space.

An Overview of Cloud Implementation in the Manufacturing Process Life Cycle

NASA Astrophysics Data System (ADS)

Kassim, Noordiana; Yusof, Yusri; Hakim Mohamad, Mahmod Abd; Omar, Abdul Halim; Roslan, Rosfuzah; Aryanie Bahrudin, Ida; Ali, Mohd Hatta Mohamed

2017-08-01

The advancement of information and communication technology (ICT) has changed the structure and functions of various sectors and it has also started to play a significant role in modern manufacturing in terms of computerized machining and cloud manufacturing. It is important for industries to keep up with the current trend of ICT for them to be able survive and be competitive. Cloud manufacturing is an approach that wanted to realize a real-world manufacturing processes that will apply the basic concept from the field of Cloud computing to the manufacturing domain called Cloud-based manufacturing (CBM) or cloud manufacturing (CM). Cloud manufacturing has been recognized as a new paradigm for manufacturing businesses. In cloud manufacturing, manufacturing companies need to support flexible and scalable business processes in the shop floor as well as the software itself. This paper provides an insight or overview on the implementation of cloud manufacturing in the modern manufacturing processes and at the same times analyses the requirements needed regarding process enactment for Cloud manufacturing and at the same time proposing a STEP-NC concept that can function as a tool to support the cloud manufacturing concept.

Macro-/Micro-Controlled 3D Lithium-Ion Batteries via Additive Manufacturing and Electric Field Processing.

PubMed

Li, Jie; Liang, Xinhua; Liou, Frank; Park, Jonghyun

2018-01-30

This paper presents a new concept for making battery electrodes that can simultaneously control macro-/micro-structures and help address current energy storage technology gaps and future energy storage requirements. Modern batteries are fabricated in the form of laminated structures that are composed of randomly mixed constituent materials. This randomness in conventional methods can provide a possibility of developing new breakthrough processing techniques to build well-organized structures that can improve battery performance. In the proposed processing, an electric field (EF) controls the microstructures of manganese-based electrodes, while additive manufacturing controls macro-3D structures and the integration of both scales. The synergistic control of micro-/macro-structures is a novel concept in energy material processing that has considerable potential for providing unprecedented control of electrode structures, thereby enhancing performance. Electrochemical tests have shown that these new electrodes exhibit superior performance in their specific capacity, areal capacity, and life cycle.

Computer Simulation of Replaceable Many Sider Plates (RMSP) with Enhanced Chip-Breaking Characteristics

NASA Astrophysics Data System (ADS)

Korchuganova, M.; Syrbakov, A.; Chernysheva, T.; Ivanov, G.; Gnedasch, E.

2016-08-01

Out of all common chip curling methods, a special tool face form has become the most widespread which is developed either by means of grinding or by means of profile pressing in the production process of RMSP. Currently, over 15 large tool manufacturers produce tools using instrument materials of over 500 brands. To this, we must add a large variety of tool face geometries, which purpose includes the control over form and dimensions of the chip. Taking into account all the many processed materials, specific tasks of the process planner, requirements to the quality of manufactured products, all this makes the choice of a proper tool which can perform the processing in the most effective way significantly harder. Over recent years, the nomenclature of RMSP for lathe tools with mechanical mounting has been considerably broadened by means of diversification of their faces

Improvements in Cz silicon PV module manufacturing

NASA Astrophysics Data System (ADS)

King, Richard R.; Mitchell, Kim W.; Jester, Theresa L.

1997-02-01

Work focused on reducing the cost per watt of Cz Si photovoltaic modules under Phase I of Siemens Solar Industries' DOE/NREL PVMaT 4A subcontract is described. Module cost components are analyzed and solutions to high-cost items are discussed in terms of specific module designs. The approaches of using larger cells and modules to reduce per-part processing cost, and of minimizing yield loss are particularly leveraging. Yield components for various parts of the fabrication process and various types of defects are shown, and measurements of the force required to break wafers throughout the cell fabrication sequence are given. The most significant type of yield loss is mechanical breakage. The implementation of statistical process control on key manufacturing processes at Siemens Solar Industries is described. Module configurations prototyped during Phase I of this project and scheduled to begin production in Phase II have a projected cost per watt reduction of 19%.

Dry etching technologies for the advanced binary film

NASA Astrophysics Data System (ADS)

Iino, Yoshinori; Karyu, Makoto; Ita, Hirotsugu; Yoshimori, Tomoaki; Azumano, Hidehito; Muto, Makoto; Nonaka, Mikio

2011-11-01

ABF (Advanced Binary Film) developed by Hoya as a photomask for 32 (nm) and larger specifications provides excellent resistance to both mask cleaning and 193 (nm) excimer laser and thereby helps extend the lifetime of the mask itself compared to conventional photomasks and consequently reduces the semiconductor manufacturing cost [1,2,3]. Because ABF uses Ta-based films, which are different from Cr film or MoSi films commonly used for photomask, a new process is required for its etching technology. A patterning technology for ABF was established to perform the dry etching process for Ta-based films by using the knowledge gained from absorption layer etching for EUV mask that required the same Ta-film etching process [4]. Using the mask etching system ARES, which is manufactured by Shibaura Mechatronics, and its optimized etching process, a favorable CD (Critical Dimension) uniformity, a CD linearity and other etching characteristics were obtained in ABF patterning. Those results are reported here.

Out-of-autoclave manufacturing of a stiffened thermoplastic carbon fibre PEEK panel

NASA Astrophysics Data System (ADS)

Flanagan, M.; Goggins, J.; Doyle, A.; Weafer, B.; Ward, M.; Bizeul, M.; Canavan, R.; O'Bradaigh, C.; Doyle, K.; Harrison, N.

2017-10-01

Out-of-Autoclave manufacturing methods, specifically Automated Tape Placement (ATP) and induction welding, used in the fabrication of a stiffened thermoplastic demonstrator panel, are presented in this study. The demonstrator panel consists of two stiffeners induction welded to a flat skin, to form a typical load bearing aerospace sub-component. The skin of the panel is manufactured from uni-directional Carbon Fibre (CF) Polyetheretherkeytone (PEEK) using laser assisted Automated Tape Placement (ATP) and the stiffeners are press formed from woven CF-PEEK. The stiffeners are fusion bonded to the skin using a continuous induction welding process. A susceptor material is used at the interface to ensure the required heating is concentrated at the weldline. Microscopy was used to examine the manufactured coupons for defects. Destructive testing was carried out to evaluate the strength of the overall assembly. The work shows that assemblies manufactured using continuous induction welding and ATP are suitable for load bearing aerospace applications.

Design concepts for a composite door frame system for general automotive applications

NASA Technical Reports Server (NTRS)

Tauber, J. A.

1976-01-01

Conceptual design, manufacturing process, and costs are explored to determine the feasibility of replacing present steel parts in automotive door structures with various composite materials. The problems of conforming to present anti-intrusion specifications with advanced materials are examined and discussed. Modest weight reductions, at competitive costs, were identified for the utilization of specific composite materials in automotive door structures.

CdSe TFT AMLCDE manufacturing process

NASA Astrophysics Data System (ADS)

Pritchard, Annette M.

1995-06-01

Active Matrix Liquid Crystal Displays, AMLCDs, based on Cadmium Selenide Thin Film Transistors, have been developed by Litton for a number of defence/avionics applications. Fabrication processed for the thin film transistor (TFT) arrays, color filters and liquid crystal cell assembly have been developed which enable the end product to meet the difficult environmental and performance specifications of military applications, while maintaining focus on cost and yield issues. The fabrication of the AMLCD products is now transitioning into a new production facility which has been designed specifically to meet the requirements of the defence/avionics marketplace.

Turnkey CAD/CAM systems' integration with IPAD systems

NASA Technical Reports Server (NTRS)

Blauth, R. E.

1980-01-01

Today's commercially available turnkey CAD/CAM systems provide a highly interactive environment, and support many specialized application functions for the design/drafting/manufacturing process. This paper presents an overview of several aerospace companies which have successfully integrated turnkey CAD/CAM systems with their own company wide engineering and manufacturing systems. It also includes a vendor's view of the benefits as well as the disadvantages of such integration efforts. Specific emphasis is placed upon the selection of standards for representing geometric engineering data and for communicating such information between different CAD/CAM systems.

40 CFR 723.175 - Chemical substances used in or for the manufacture or processing of instant photographic and peel...

Code of Federal Regulations, 2010 CFR

2010-07-01

... manufacture and processing in the special production area. All manufacturing, processing, and use operations... shape or design during manufacture, (ii) which has end use function(s) dependent in whole or in part... production area, the ambient air concentration of the new chemical substance during manufacture, processing...

Integrated Dynamic Process Planning and Scheduling in Flexible Manufacturing Systems via Autonomous Agents

NASA Astrophysics Data System (ADS)

Nejad, Hossein Tehrani Nik; Sugimura, Nobuhiro; Iwamura, Koji; Tanimizu, Yoshitaka

Process planning and scheduling are important manufacturing planning activities which deal with resource utilization and time span of manufacturing operations. The process plans and the schedules generated in the planning phase shall be modified in the execution phase due to the disturbances in the manufacturing systems. This paper deals with a multi-agent architecture of an integrated and dynamic system for process planning and scheduling for multi jobs. A negotiation protocol is discussed, in this paper, to generate the process plans and the schedules of the manufacturing resources and the individual jobs, dynamically and incrementally, based on the alternative manufacturing processes. The alternative manufacturing processes are presented by the process plan networks discussed in the previous paper, and the suitable process plans and schedules are searched and generated to cope with both the dynamic status and the disturbances of the manufacturing systems. We initiatively combine the heuristic search algorithms of the process plan networks with the negotiation protocols, in order to generate suitable process plans and schedules in the dynamic manufacturing environment. A simulation software has been developed to carry out case studies, aimed at verifying the performance of the proposed multi-agent architecture.

Sustainable manufacturing by calculating the energy demand during turning of AISI 1045 steel

NASA Astrophysics Data System (ADS)

Nur, R.; Nasrullah, B.; Suyuti, M. A.; Apollo

2018-01-01

Sustainable development will become important issues for many fields, including production, industry, and manufacturing. In order to achieve sustainable development, industry should be able to perform of sustainable production processes and environmentally friendly. Therefore, there is need to minimize the energy demand in the machining process. This paper presents a calculation method of energy consumption in the machining process, especially turning process which calculated by summing the number of energy consumption, such as the electric energy consumed during the machining preparation, the electrical energy during the cutting processes, and the electrical energy to produce a cutting tool. A case study was performed on dry turning of mild carbon steel using coated carbide. This approach can be used to determine the total amount of electrical energy consumed in the specific machining process. It concluded that the energy consumption will be an increase for using the high cutting speed as well as for the feed rate was increased.

Lightweight bio-composites based on hemp fibres produced by conventional and unconventional processes

NASA Astrophysics Data System (ADS)

Boccarusso, L.; Durante, M.; Formisano, A.; Langella, A.; Minutolo, F. Memola Capece

2017-10-01

Considering that nowadays the interest in the use of bio-composite materials is increasing more and more, this work is focused on the manufacturing of lightweight components based on hemp fibres for future applications, for example as a core for sandwich structures. Three different no-complex processes were used: a conventional hand lay-up, an unconventional infusion process and a hand lay-up process followed by injection moulding. They were used to produce bio-composite structures using an epoxy resin and/or a polyurethane foam as matrix. Depending on the process used for the manufacturing, laminates with different values of density were obtained. A detailed study in terms of both static and dynamic properties was carried out and the different mechanical behaviour for each sample typology was highlighted. The results showed that the process in which both the epoxy resin and the polyurethane foam were used as matrix allowed to obtain laminates with lower density and higher specific mechanical properties.

The International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes--chapter 3: Pig islet product manufacturing and release testing.

PubMed

Korbutt, Gregory S

2009-01-01

This chapter provides recommendations on pig islet product manufacturing and release testing to scientific and corporate programs interested in future clinical studies using xenogeneic porcine pancreatic islet cell products for the treatment of type 1 diabetes.To facilitate control of manufacturing as well as reproducibility and consistency of product lots, the manufacturing process, and the manufacturing facility must be in compliance with current Good Manufacturing Practices regulations. Data must be provided to demonstrate that islet products can be consistently prepared that would meet basic lot release requirements. To facilitate product safety: (i) materials used in the manufacturing process, including the pig pancreas, must be free of adventitious agents; (ii) islets must be manufactured using aseptic processing; and (iii) final product must undergo tests for sterility, mycoplasma (if cultured) and endotoxin. Safety specifications for pig islet product release include a negative Gram stain and an endotoxin content of <5.0 EU/kg recipient body weight. Product post-release assessments must include sterility cultures on the final product. Because results for sterility are available only retrospectively, a plan of action must be in place for patient notification and treatment in case the sterility culture results are positive for contamination. Product characterization information must address important aspects of lot release testing such as identity/purity (cell composition), quantity [islet equivalents (IE), cell number] and potency (insulin secretory capacity, oxygen consumption rate corrected for DNA or transplant bioassay in immunoincompetent diabetic mice). This information is also critical to demonstrate manufacturing control and product consistency across multiple islet preparations (lots). Providing islet products containing an islet mass sufficient to restore euglycemia in trial participants (>or=10 000 IE/kg) requires pooling of islets from multiple donor pancreata (two to four from adult donors and seven to 10 from neonatal donors). Demonstration of product consistency across products from individual pancreata would warrant release testing to be performed on a sample of the pooled product. As product development and clinical trials advance, the increasingly more detailed specifications of potency assays on adult porcine islet products are expected to be predictive of post-transplant glycemic control. The immaturity of fetal and neonatal porcine islet tissue precludes the use of in vitro insulin secretion as a potency test as part of lot release testing; another measure of potency appropriate to fetal and neonatal cells will need to be developed for product release testing and evaluation of aliquots of these products in mouse transplant bioassays should be performed to provide meaningful post-release information.

Rice straw-wood particle composite for sound absorbing wooden construction materials.

PubMed

Yang, Han-Seung; Kim, Dae-Jun; Kim, Hyun-Joong

2003-01-01

In this study, rice straw-wood particle composite boards were manufactured as insulation boards using the method used in the wood-based panel industry. The raw material, rice straw, was chosen because of its availability. The manufacturing parameters were: a specific gravity of 0.4, 0.6, and 0.8, and a rice straw content (10/90, 20/80, and 30/70 weight of rice straw/wood particle) of 10, 20, and 30 wt.%. A commercial urea-formaldehyde adhesive was used as the composite binder, to achieve 140-290 psi of bending modulus of rupture (MOR) with 0.4 specific gravity, 700-900 psi of bending MOR with 0.6 specific gravity, and 1400-2900 psi of bending MOR with a 0.8 specific gravity. All of the composite boards were superior to insulation board in strength. Width and length of the rice straw particle did not affect the bending MOR. The composite boards made from a random cutting of rice straw and wood particles were the best and recommended for manufacturing processes. Sound absorption coefficients of the 0.4 and 0.6 specific gravity boards were higher than the other wood-based materials. The recommended properties of the rice straw-wood particle composite boards are described, to absorb noises, preserve the temperature of indoor living spaces, and to be able to partially or completely substitute for wood particleboard and insulation board in wooden constructions.

Multivariate statistical process control in product quality review assessment - A case study.

PubMed

Kharbach, M; Cherrah, Y; Vander Heyden, Y; Bouklouze, A

2017-11-01

According to the Food and Drug Administration and the European Good Manufacturing Practices (GMP) guidelines, Annual Product Review (APR) is a mandatory requirement in GMP. It consists of evaluating a large collection of qualitative or quantitative data in order to verify the consistency of an existing process. According to the Code of Federal Regulation Part 11 (21 CFR 211.180), all finished products should be reviewed annually for the quality standards to determine the need of any change in specification or manufacturing of drug products. Conventional Statistical Process Control (SPC) evaluates the pharmaceutical production process by examining only the effect of a single factor at the time using a Shewhart's chart. It neglects to take into account the interaction between the variables. In order to overcome this issue, Multivariate Statistical Process Control (MSPC) can be used. Our case study concerns an APR assessment, where 164 historical batches containing six active ingredients, manufactured in Morocco, were collected during one year. Each batch has been checked by assaying the six active ingredients by High Performance Liquid Chromatography according to European Pharmacopoeia monographs. The data matrix was evaluated both by SPC and MSPC. The SPC indicated that all batches are under control, while the MSPC, based on Principal Component Analysis (PCA), for the data being either autoscaled or robust scaled, showed four and seven batches, respectively, out of the Hotelling T 2 95% ellipse. Also, an improvement of the capability of the process is observed without the most extreme batches. The MSPC can be used for monitoring subtle changes in the manufacturing process during an APR assessment. Copyright © 2017 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

Performance testing of a prototype Pd-Ag diffuser

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morgan, G. A.; Hodge, B. J.

The fusion fuel cycle has gained significant attention over the last decade as interest in fusion programs has increased. One of the critical components of the fusion process is the tritium fuel cycle. The tritium fuel cycle is designed to supply and recycle process tritium at a specific throughput rate. One of the most important processes within the tritium fuel cycle is the clean-up of the of the process tritium. This step will initially separate the hydrogen isotopes (H2, D2, and T2) from the rest of the process gas using Pd-Ag diffusers or permeators. The Pd-Ag diffuser is an integralmore » component for any tritium purification system; whether part of the United States’ defense mission or fusion programs. Domestic manufacturers of Pd-Ag diffusers are extremely limited and only a few manufacturers exist. Johnson-Matthey (JM) Pd-Ag diffusers (permeators) have previously been evaluated for the separation of hydrogen isotopes from non-hydrogen gas species in the process. JM is no longer manufacturing Pd-Ag diffusers and a replacement vendor needs to be identified to support future needs. A prototype Pd-Ag diffuser has been manufactured by Power and Energy, and is considered a potential replacement for the JM diffuser for tritium service. New diffuser designs for a tritium facility for any fusion energy applications must be characterized by evaluating their operating envelope prior to installation in a tritium processing facility. The prototype Pd-Ag diffuser was characterized to determine the overall performance as a function of the permeation of hydrogen through the membrane. The tests described in this report consider the effects of feed gas compositions, feed flow rates, pump configuration and internal tube pressure on the permeation of H2 through the Pd-Ag tubes.« less

21 CFR 814.3 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... (d) Master file means a reference source that a person submits to FDA. A master file may contain detailed information on a specific manufacturing facility, process, methodology, or component used in the... for a class III medical device, including all information submitted with or incorporated by reference...

Fatigue resistance of engine-driven rotary nickel-titanium instruments produced by new manufacturing methods.

PubMed

Gambarini, Gianluca; Grande, Nicola Maria; Plotino, Gianluca; Somma, Francesco; Garala, Manish; De Luca, Massimo; Testarelli, Luca

2008-08-01

The aim of the present study was to investigate whether cyclic fatigue resistance is increased for nickel-titanium instruments manufactured by using new processes. This was evaluated by comparing instruments produced by using the twisted method (TF; SybronEndo, Orange, CA) and those using the M-wire alloy (GTX; Dentsply Tulsa-Dental Specialties, Tulsa, OK) with instruments produced by a traditional NiTi grinding process (K3, SybronEndo). Tests were performed with a specific cyclic fatigue device that evaluated cycles to failure of rotary instruments inside curved artificial canals. Results indicated that size 06-25 TF instruments showed a significant increase (p < 0.05) in the mean number of cycles to failure when compared with size 06-25 K3 files. Size 06-20 K3 instruments showed no significant increase (p > 0.05) in the mean number of cycles to failure when compared with size 06-20 GT series X instruments. The new manufacturing process produced nickel-titanium rotary files (TF) significantly more resistant to fatigue than instruments produced with the traditional NiTi grinding process. Instruments produced with M-wire (GTX) were not found to be more resistant to fatigue than instruments produced with the traditional NiTi grinding process.

Towards the implementation of quality by design to the production of therapeutic monoclonal antibodies with desired glycosylation patterns.

PubMed

del Val, Ioscani Jimenez; Kontoravdi, Cleo; Nagy, Judit M

2010-01-01

Quality by design (QbD) is a scheme for the development, manufacture, and approval of pharmaceutical products. The end goal of QbD is to ensure product quality by building it into the manufacturing process. The main regulatory bodies are encouraging its implementation to the manufacture of all new pharmaceuticals including biological products. Monoclonal antibodies (mAbs) are currently the leading products of the biopharmaceutical industry. It has been widely reported that glycosylation directly influences the therapeutic mechanisms by which mAbs function in vivo. In addition, glycosylation has been identified as one of the main sources of monoclonal antibody heterogeneity, and thus, a critical parameter to follow during mAb manufacture. This article reviews the research on glycosylation of mAbs over the past 2 decades under the QbD scope. The categories presented under this scope are: (a) definition of the desired clinical effects of mAbs, (b) definition of the glycosylation-associated critical quality attributes (glycCQAs) of mAbs, (c) assessment of process parameters that pose a risk for mAb glycCQAs, and (d) methods for accurately quantifying glycCQAs of mAbs. The information available in all four areas leads us to conclude that implementation of QbD to the manufacture of mAbs with specific glycosylation patterns will be a reality in the near future. We also foresee that the implementation of QbD will lead to the development of more robust and efficient manufacturing processes and to a new generation of mAbs with increased clinical efficacy. Copyright © 2010 American Institute of Chemical Engineers (AIChE).

Opportunities for Collaboration at the Interface of Pharmacovigilance and Manufacturing.

PubMed

Beninger, Paul

2017-04-01

A case can be made that much common ground exists between pharmacovigilance and pharmaceutical manufacturing. Of the 8 major US statutes that shaped the pharmaceutical industry since early in the 20th Century, 7 followed fatally catastrophic events related to the use of a manufactured product, and 1 followed the discovery of a counterfeit product. To facilitate an understanding of the interplay between pharmacovigilance and manufacturing, it is convenient to divide manufacturing into 3 categories: (1) upstream sourcing of materials: pharmacovigilance plays an important role when adverse event clusters are seen during routine vigilance detection processes and the suspicion turns to possibly contaminated source material, (2) the manufacturing process itself: pharmacovigilance may be called on to conduct a health hazard evaluation if a manufacturing deviation is detected after product release (the assessment can inform the depth of a recall), and (3) downstream distribution and product use: there is only light regulation of the interval between product distribution after manufacturing release and just before administration to patients, a time during which product may be subject to an out-of-specification determination for environmental controls or subject to malfeasant activities, such as counterfeit substitution or product diversion. Recently introduced statutory remedies, including the FDA Safety and Innovation Act and the Drug Supply Chain Security Act in the United States and the Falsified Medicines Directive (directive 2011/62/EC) in the European Union, can provide capabilities to support pharmacovigilance signal management activities that have the potential to reduce the risk to patients of experiencing adverse events caused by counterfeit, diverted, or tampered product. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Cartilage Tissue Engineering with Silk Fibroin Scaffolds Fabricated by Indirect Additive Manufacturing Technology

PubMed Central

Chen, Chih-Hao; Liu, Jolene Mei-Jun; Chua, Chee-Kai; Chou, Siaw-Meng; Shyu, Victor Bong-Hang; Chen, Jyh-Ping

2014-01-01

Advanced tissue engineering (TE) technology based on additive manufacturing (AM) can fabricate scaffolds with a three-dimensional (3D) environment suitable for cartilage regeneration. Specifically, AM technology may allow the incorporation of complex architectural features. The present study involves the fabrication of 3D TE scaffolds by an indirect AM approach using silk fibroin (SF). From scanning electron microscopic observations, the presence of micro-pores and interconnected channels within the scaffold could be verified, resulting in a TE scaffold with both micro- and macro-structural features. The intrinsic properties, such as the chemical structure and thermal characteristics of SF, were preserved after the indirect AM manufacturing process. In vitro cell culture within the SF scaffold using porcine articular chondrocytes showed a steady increase in cell numbers up to Day 14. The specific production (per cell basis) of the cartilage-specific extracellular matrix component (collagen Type II) was enhanced with culture time up to 12 weeks, indicating the re-differentiation of chondrocytes within the scaffold. Subcutaneous implantation of the scaffold-chondrocyte constructs in nude mice also confirmed the formation of ectopic cartilage by histological examination and immunostaining. PMID:28788558

Mechanical design implementation and mathematical considerations for ultra precise diamond turning of multiple freeform mirrors on a common substrate

NASA Astrophysics Data System (ADS)

Hartung, Johannes; Beier, Matthias; Peschel, Thomas; Gebhardt, Andreas; Risse, Stefan

2015-09-01

For optical systems consisting of metal (in general freeform) mirrors there exist several diamond turning fabrication approaches. These are distuingished by the effort in manufacturing and integration of the later system. The more work one puts into the manufacturing stage the less complicated is the alignment and integration afterwards. For example the most degrees of freedom have to be aligned in integration phase if every mirror of the system is fabricated as a single optical component. For a three mirror anastigmat with three freeform mirrors the degrees of freedom sum up to 18. Therefore the mirror fabrication itself is more or less easy, but the integration is very difficult. There are three major parts in the design and manufacturing process chain to be considered for tackling this integration problem. At the first position in the process chain there is the optical design occuring. At this stage a negotiation between manufacturing and design could improve manufacturability because of more possible integration approaches. The second stage is the mechanical design. Here the appropriate manufacturing approach is already chosen, but may be revisited due to incompatiblities with, e.g., stress specifications. The third level is the manufacturing stage. Here are different clamping approaches and fabrication methods possible. The current article will focus on an approach ("snap-together") where two mirrors are fabricated on one substrate and therefore a reduction of the number of degrees of freedom to be aligned are reduced to six. This improves the amount of time needed for the system integration significantly in contrast to a single mirror fabrication.

Department of Energy. Jobs and Innovation Accelerator Challenge (JIAC) Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Riley, Jon

1.1 NCMS Digital Manufacturing Initiative The people and businesses of Southeast Michigan have long been known for their prowess in the automotive industry, a sector built on the innovation of the assembly line and the rise of mass production as a manufacturing model. Just as the assembly line was the key to a strong manufacturing base a century ago, a digital manufacturing infrastructure is critical to the future of industry. Economic uncertainty has slowed innovation, but access to cutting-edge tools such as high performance modeling, simulation and analysis (MSA) provides a bold path forward, ensuring global competitiveness and transforming ourmore » manufacturing processes. Digital manufacturing is, essentially, the virtualization of processes that had been physical. Many larger manufacturers have embraced it, but the majority of small and medium-sized manufacturers (SMMs) have not. The Digital Manufacturing Initiative is a bold, national effort by the National Center for Manufacturing Sciences (NCMS) to put manufacturing innovation on fast forward, and bring the future of industry into the present. SMMs need a broader array of access options, training, support, and guidance. Providing access will supercharge any organization with tomorrow’s tools, as positively disruptive and potential-laden as the assembly line once was. Sustainable success in the State of Michigan requires the development of foundational infrastructure, the exploration of initial inroads with various manufacturers of all sizes, and the initiation of a prototype engagement mechanism applicable for other future regional efforts. To accomplish this NCMS leveraged complimen-tary State and Federal funding opportunities (shown in Figure 1) along with a coupled voice of industry market research study. A brief summary of each opportunity is found in Appendix A. At the heart of the Michigan effort was the development of an access portal (www.doitindigital.com) and the development of partnerships with local large manufacturers (OEMs) who could provide pull to encourage SMMs (current and future suppliers) to participate. Central to this entire effort was the opportunity that this Final Report documents corresponding to the specific tasks associated with the U.S. Department of Energy (DOE) funded component of the InnoState Jobs Innovation Accelerator Challenge (JIAC) Program.« less

Advanced optical manufacturing digital integrated system

NASA Astrophysics Data System (ADS)

Tao, Yizheng; Li, Xinglan; Li, Wei; Tang, Dingyong

2012-10-01

It is necessarily to adapt development of advanced optical manufacturing technology with modern science technology development. To solved these problems which low of ration, ratio of finished product, repetition, consistent in big size and high precision in advanced optical component manufacturing. Applied business driven and method of Rational Unified Process, this paper has researched advanced optical manufacturing process flow, requirement of Advanced Optical Manufacturing integrated System, and put forward architecture and key technology of it. Designed Optical component core and Manufacturing process driven of Advanced Optical Manufacturing Digital Integrated System. the result displayed effective well, realized dynamic planning Manufacturing process, information integration improved ratio of production manufactory.

WHO Expert Committee on Specifications for Pharmaceutical Preparations.

PubMed

2011-01-01

The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use: procedure for adoption of International Chemical Reference Substances; WHO good practices for pharmaceutical microbiology laboratories; good manufacturing practices: main principles for pharmaceutical products; good manufacturing practices for blood establishments (jointly with the Expert Committee on Biological Standardization); guidelines on good manufacturing practices for heating, ventilation and air-conditioning systems for non-sterile pharmaceutical dosage forms; good manufacturing practices for sterile pharmaceutical products; guidelines on transfer of technology in pharmaceutical manufacturing; good pharmacy practice: standards for quality of pharmacy services (joint FIP/WHO); model guidance for the storage and transport of time- and temperature-sensitive pharmaceutical products (jointly with the Expert Committee on Biological Standardization); procedure for prequalification of pharmaceutical products; guide on submission of documentation for prequalification of innovator finished pharmaceutical products approved by stringent regulatory authorities; prequalification of quality control laboratories: procedure for assessing the acceptability, in principle, of quality control laboratories for use by United Nations agencies; guidelines for preparing a laboratory information file; guidelines for drafting a site master file; guidelines on submission of documentation for a multisource (generic) finished product: general format: preparation of product dossiers in common technical document format.

The characterisation of Bacillus spores occurring in the manufacturing of (low acid) canned products.

PubMed

Oomes, S J C M; van Zuijlen, A C M; Hehenkamp, J O; Witsenboer, H; van der Vossen, J M B M; Brul, S

2007-11-30

Spore-forming bacteria can be a problem in the food industry, especially in the canning industry. Spores present in ingredients or present in the processing environment severely challenge the preservation process since their thermal resistance may be very high. We therefore asked the question which bacterial spore formers are found in a typical soup manufacturing plant, where they originate from and what the thermal resistance of their spores is. To answer these questions molecular techniques for bacterial species and strain identification were used as well as a protocol for the assessment of spore heat stress resistance based on the Kooiman method. The data indicate the existence and physiological cause of the high thermal resistance of spores of many of the occurring species. In particular it shows that ingredients used in soup manufacturing are a rich source of high thermal resistant spores and that sporulation in the presence of ingredients rich in divalent metal ions exerts a strong influence on spore heat resistance. It was also indicated that Bacillus spores may well be able to germinate and resporulate during manufacturing i.e. through growth and sporulation in line. Both these spores and those originating from the ingredients were able to survive certain thermal processing settings. Species identity was confirmed using fatty acid analysis, 16SrRNA gene sequencing and DNA-DNA hybridisation. Finally, molecular typing experiments using Ribotyping and AFLP analysis show that strains within the various Bacillus species can be clustered according to the thermal resistance properties of their spores. AFLP performed slightly better than Ribotyping. The data proofed to be useful for the generation of strain specific probes. Protocols to validate these probes in routine identification and innovation aimed at tailor made heat processing in soup manufacturing have been formulated.

40 CFR 53.51 - Demonstration of compliance with design specifications and manufacturing and test requirements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... compliance with design specifications and manufacturing and test requirements. (a) Overview. (1) Paragraphs... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Demonstration of compliance with design specifications and manufacturing and test requirements. 53.51 Section 53.51 Protection of Environment...

Manufacturing Process Selection of Composite Bicycle’s Crank Arm using Analytical Hierarchy Process (AHP)

NASA Astrophysics Data System (ADS)

Luqman, M.; Rosli, M. U.; Khor, C. Y.; Zambree, Shayfull; Jahidi, H.

2018-03-01

Crank arm is one of the important parts in a bicycle that is an expensive product due to the high cost of material and production process. This research is aimed to investigate the potential type of manufacturing process to fabricate composite bicycle crank arm and to describe an approach based on analytical hierarchy process (AHP) that assists decision makers or manufacturing engineers in determining the most suitable process to be employed in manufacturing of composite bicycle crank arm at the early stage of the product development process to reduce the production cost. There are four types of processes were considered, namely resin transfer molding (RTM), compression molding (CM), vacuum bag molding and filament winding (FW). The analysis ranks these four types of process for its suitability in the manufacturing of bicycle crank arm based on five main selection factors and 10 sub factors. Determining the right manufacturing process was performed based on AHP process steps. Consistency test was performed to make sure the judgements are consistent during the comparison. The results indicated that the compression molding was the most appropriate manufacturing process because it has the highest value (33.6%) among the other manufacturing processes.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

The Performance Prototype Trough (PPT) Concentrating Collector consists of four 80-foot modules in a 320-foot row. The collector was analyzed, including cost estimates and manufacturing processes to produce collectors in volumes from 100 to 100,000 modules per year. The four different reflector concepts considered were the sandwich reflector structure, sheet metal reflector structure, molded reflector structure, and glass laminate structure. The sheet metal and glass laminate structures are emphasized with their related structure concepts. A preliminary manufacturing plan is offered that includes: documentation of the manufacturing process with production flow diagrams; labor and material costs at various production levels; machinerymore » and equipment requirements including preliminary design specifications; and capital investment costs for a new plant. Of five reflector designs considered, the two judged best and considered at length are thin annealed glass and steel laminate on steel frame panel and thermally sagged glass. Also discussed are market considerations, costing and selling price estimates, design cost analysis and make/buy analysis. (LEW)« less

Fine pitch thermosonic wire bonding: analysis of state-of-the-art manufacturing capability

NASA Astrophysics Data System (ADS)

Cavasin, Daniel

1995-09-01

A comprehensive process characterization was performed at the Motorola plastic package assembly site in Selangor, Malaysia, to document the current fine pitch wire bond process capability, using state-of-the-art equipment, in an actual manufacturing environment. Two machines, representing the latest technology from two separate manufacturers, were operated one shift per day for five days, bonding a 132 lead Plastic Quad Flat Pack. Using a test device specifically designed for fine pitch wire bonding, the bonding programs were alternated between 107 micrometers and 92 micrometers pad pitch, running each pitch for a total of 1600 units per machine. Wire, capillary type, and related materials were standardized and commercially available. A video metrology measurement system, with a demonstrated six sigma repeatability band width of 0.51 micrometers , was utilized to measure the bonded units for bond dimensions and placement. Standard Quality Assurance (QA) metrics were also performed. Results indicate that state-of-the-art thermosonic wire bonding can achieve acceptable assembly yields at these fine pad pitches.

Aerospace Environmental Technology Conference: Exectutive summary

NASA Technical Reports Server (NTRS)

Whitaker, A. F. (Editor)

1995-01-01

The mandated elimination of CFC's, Halons, TCA, and other ozone depleting chemicals and specific hazardous materials has required changes and new developments in aerospace materials and processes. The aerospace industry has been involved for several years in providing product substitutions, redesigning entire production processes, and developing new materials that minimize or eliminate damage to the environment. These activities emphasize replacement cleaning solvents and their application verifications, compliant coatings including corrosion protection systems, and removal techniques, chemical propulsion effects on the environment, and the initiation of modifications to relevant processing and manufacturing specifications and standards. The papers from this conference are being published in a separate volume as NASA CP-3298.

Sustainable Energy Solutions Task 3.0:Life-Cycle Database for Wind Energy Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Twomey, Janet M.

2010-03-01

The benefits of wind energy had previously been captured in the literature at an overview level with relatively low transparency or ability to understand the basis for that information. This has limited improvement and decision-making to larger questions such as wind versus other electrical sources (such as coal-fired plants). This research project has established a substantially different approach which is to add modular, high granularity life cycle inventory (lci) information that can be used by a wide range of decision-makers, seeking environmental improvement. Results from this project have expanded the understanding and evaluation of the underlying factors that can improvemore » both manufacturing processes and specifically wind generators. The use of life cycle inventory techniques has provided a uniform framework to understand and compare the full range of environmental improvement in manufacturing, hence the concept of green manufacturing. In this project, the focus is on 1. the manufacturing steps that transform materials and chemicals into functioning products 2. the supply chain and end-of-life influences of materials and chemicals used in industry Results have been applied to wind generators, but also impact the larger U.S. product manufacturing base. For chemicals and materials, this project has provided a standard format for each lci that contains an overview and description, a process flow diagram, detailed mass balances, detailed energy of unit processes, and an executive summary. This is suitable for integration into other life cycle databases (such as that at NREL), so that broad use can be achieved. The use of representative processes allows unrestricted use of project results. With the framework refined in this project, information gathering was initiated for chemicals and materials in wind generation. Since manufacturing is one of the most significant parts of the environmental domain for wind generation improvement, this project research has developed a fundamental approach. The emphasis was place on individual unit processes as an organizing framework to understand the life cycle of manufactured products. The rearrangement of unit processes provides an efficient and versatile means of understanding improved manufactured products such as wind generators. The taxonomy and structure of unit process lci were developed in this project. A series of ten unit process lci were developed to sample the major segments of the manufacturing unit process taxonomy. Technical and economic effectiveness has been a focus of the project research in Task three. The use of repeatable modules for the organization of information on environmental improvement has a long term impact. The information developed can be used and reused in a variety of manufacturing plants and for a range of wind generator sizes and designs. Such a modular approach will lower the cost of life cycle analysis, that is often asked questions of carbon footprint, environmental impact, and sustainability. The use of a website for dissemination, linked to NREL, adds to the economic benefit as more users have access to the lci information. Benefit to the public has been achieved by a well-attended WSU conference, as well as presentations for the Kansas Wind Energy Commission. Attendees represented public interests, land owners, wind farm developers, those interested in green jobs, and industry. Another benefit to the public is the start of information flow from manufacturers that can inform individuals about products.« less

Laser materials processing of complex components: from reverse engineering via automated beam path generation to short process development cycles

NASA Astrophysics Data System (ADS)

Görgl, Richard; Brandstätter, Elmar

2017-01-01

The article presents an overview of what is possible nowadays in the field of laser materials processing. The state of the art in the complete process chain is shown, starting with the generation of a specific components CAD data and continuing with the automated motion path generation for the laser head carried by a CNC or robot system. Application examples from laser cladding and laser-based additive manufacturing are given.

Using the scanning electron microscope on the production line to assure quality semiconductors

NASA Technical Reports Server (NTRS)

Adolphsen, J. W.; Anstead, R. J.

1972-01-01

The use of the scanning electron microscope to detect metallization defects introduced during batch processing of semiconductor devices is discussed. A method of determining metallization integrity was developed which culminates in a procurement specification using the scanning microscope on the production line as a quality control tool. Batch process control of the metallization operation is monitored early in the manufacturing cycle.

Spray Deposition: A Fundamental Study of Droplet Impingement, Spreading and Consolidation

DTIC Science & Technology

1989-12-01

low alloy (HSLA) steel. Preforms of HSLA-100, a low carbon bainitic, copper precipitation strengthened HSLA steel...manufacturing process. Specifically, HSLA-100, a copper precipitation strengthened high-strength, low - alloy steel was spray cast via the Osprey’ m process...by spray casting. Preforms of HSLA-100, a low carbon bainitic, copper precipitation strengthened steel, were spray cast under differing conditions

Evaluation of an Al-Ce alloy for laser additive manufacturing

DOE PAGES

Plotkowski, A.; Rios, O.; Sridharan, N.; ...

2016-12-27

Our present research in metal additive manufacturing (AM) focuses on designing processing parameters around existing alloys designed for traditional manufacturing. However, to maximize the benefits of AM, alloys should be designed to specifically take advantage of the unique thermal conditions of these processes. Furthermore, our study focuses on the development of a design methodology for alloys in AM, using a newly developed Al-Ce alloy as an initial case study. To evaluate the candidacy of this system for fusion based additive manufacturing, single-line laser melts were made on cast Al-12Ce plates using three different beam velocities (100, 200, and 300 mm/min).more » The microstructure was evaluated in the as-melted and heat treated conditions (24 hrs at 300°C). An extremely fine microstructure was observed within the weld pools, evolving from eutectic at the outer solid-liquid boundaries to a primary Al FCC dendritic/cellular structure nearer the melt-pool centerline. We rationalized the observed microstructures through the construction of a microstructure selection map for the Al-Ce binary system, which will be used to enable future alloy design. Interestingly, the heat treated samples exhibited no microstructural coarsening.« less

Load-adaptive scaffold architecturing: a bioinspired approach to the design of porous additively manufactured scaffolds with optimized mechanical properties.

PubMed

Rainer, Alberto; Giannitelli, Sara M; Accoto, Dino; De Porcellinis, Stefano; Guglielmelli, Eugenio; Trombetta, Marcella

2012-04-01

Computer-Aided Tissue Engineering (CATE) is based on a set of additive manufacturing techniques for the fabrication of patient-specific scaffolds, with geometries obtained from medical imaging. One of the main issues regarding the application of CATE concerns the definition of the internal architecture of the fabricated scaffolds, which, in turn, influences their porosity and mechanical strength. The present study envisages an innovative strategy for the fabrication of highly optimized structures, based on the a priori finite element analysis (FEA) of the physiological load set at the implant site. The resulting scaffold micro-architecture does not follow a regular geometrical pattern; on the contrary, it is based on the results of a numerical study. The algorithm was applied to a solid free-form fabrication process, using poly(ε-caprolactone) as the starting material for the processing of additive manufactured structures. A simple and intuitive geometry was chosen as a proof-of-principle application, on which finite element simulations and mechanical testing were performed. Then, to demonstrate the capability in creating mechanically biomimetic structures, the proximal femur subjected to physiological loading conditions was considered and a construct fitting a femur head portion was designed and manufactured.

Integration of design and inspection

NASA Astrophysics Data System (ADS)

Simmonds, William H.

1990-08-01

Developments in advanced computer integrated manufacturing technology, coupled with the emphasis on Total Quality Management, are exposing needs for new techniques to integrate all functions from design through to support of the delivered product. One critical functional area that must be integrated into design is that embracing the measurement, inspection and test activities necessary for validation of the delivered product. This area is being tackled by a collaborative project supported by the UK Government Department of Trade and Industry. The project is aimed at developing techniques for analysing validation needs and for planning validation methods. Within the project an experimental Computer Aided Validation Expert system (CAVE) is being constructed. This operates with a generalised model of the validation process and helps with all design stages: specification of product requirements; analysis of the assurance provided by a proposed design and method of manufacture; development of the inspection and test strategy; and analysis of feedback data. The kernel of the system is a knowledge base containing knowledge of the manufacturing process capabilities and of the available inspection and test facilities. The CAVE system is being integrated into a real life advanced computer integrated manufacturing facility for demonstration and evaluation.

Application of lean manufacturing techniques in the Emergency Department.

PubMed

Dickson, Eric W; Singh, Sabi; Cheung, Dickson S; Wyatt, Christopher C; Nugent, Andrew S

2009-08-01

"Lean" is a set of principles and techniques that drive organizations to continually add value to the product they deliver by enhancing process steps that are necessary, relevant, and valuable while eliminating those that fail to add value. Lean has been used in manufacturing for decades and has been associated with enhanced product quality and overall corporate success. To evaluate whether the adoption of Lean principles by an Emergency Department (ED) improves the value of emergency care delivered. Beginning in December 2005, we implemented a variety of Lean techniques in an effort to enhance patient and staff satisfaction. The implementation followed a six-step process of Lean education, ED observation, patient flow analysis, process redesign, new process testing, and full implementation. Process redesign focused on generating improvement ideas from frontline workers across all departmental units. Value-based and operational outcome measures, including patient satisfaction, expense per patient, ED length of stay (LOS), and patient volume were compared for calendar year 2005 (pre-Lean) and periodically after 2006 (post-Lean). Patient visits increased by 9.23% in 2006. Despite this increase, LOS decreased slightly and patient satisfaction increased significantly without raising the inflation adjusted cost per patient. Lean improved the value of the care we delivered to our patients. Generating and instituting ideas from our frontline providers have been the key to the success of our Lean program. Although Lean represents a fundamental change in the way we think of delivering care, the specific process changes we employed tended to be simple, small procedure modifications specific to our unique people, process, and place. We, therefore, believe that institutions or departments aspiring to adopt Lean should focus on the core principles of Lean rather than on emulating specific process changes made at other institutions.

Environmental life cycle assessment of Italian mozzarella cheese: Hotspots and improvement opportunities.

PubMed

Dalla Riva, A; Burek, J; Kim, D; Thoma, G; Cassandro, M; De Marchi, M

2017-10-01

The present study investigated a cradle-to-grave life cycle assessment to estimate the environmental impacts associated with Italian mozzarella cheese consumption. The differences between mozzarella produced from raw milk and mozzarella produced from curd were studied, and differences in manufacturing processes have been emphasized in order to provide guidance for targeted improvements at this phase. Specifically, the third-largest Italian mozzarella producer was surveyed to collect site-specific manufacturing data. The Ecoinvent v3.2 database was used for secondary data, whereas SimaPro 8.1 was the modeling software. The inventory included inputs from farm activities to end of life disposal of wasted mozzarella and packaging. Additionally, plant-specific information was used to assign major inputs, such as electricity, natural gas, packaging, and chemicals to specific products; however, where disaggregated information was not provided, milk solids allocation was applied. Notably, loss of milk solids was accounted during the manufacture, moreover mozzarella waste and transport were considered during distribution, retail, and consumption phases. Feed production and animal emissions were the main drivers of raw milk production. Electricity and natural gas usage, packaging (cardboard and plastic), transport, wastewater treatment, and refrigerant loss affected the emissions from a farm gate-to-dairy plant gate perspective. Post-dairy plant gate effects were mainly determined by electricity usage for storage of mozzarella, transport of mozzarella, and waste treatment. The average emissions were 6.66 kg of CO 2 equivalents and 45.1 MJ of cumulative energy demand/kg of consumed mozzarella produced directly from raw milk, whereas mozzarella from purchased curd had larger emissions than mozzarella from raw milk due to added transport of curd from specialty manufacturing plants, as well as electricity usage from additional processes at the mozzarella plant that are required to process the curd into mozzarella. Normalization points to ecotoxicity as the impact category most significantly influenced by mozzarella consumption. From a farm gate-to-grave perspective, ecotoxicity and freshwater and marine eutrophication are the first and second largest contributors of mozzarella consumption to average European effects, respectively. To increase environmental sustainability, an improvement of efficiency for energy and packaging usage and transport activities is recommended in the post-farm gate mozzarella supply chain. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Human exposure modeling in a life cycle framework for chemicals and products

EPA Science Inventory

A chemical enters into commerce to serve a specific function in a product or process. This decision triggers both the manufacture of the chemical and its potential release over the life cycle of the product. Efficiently evaluating chemical safety and sustainability requires combi...

77 FR 23618 - Authority To Manufacture and Distribute Postage Evidencing Systems

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-20

... revision of the rules concerning inventory controls for Postage Evidencing Systems (PES). These changes are... System inventory control processes. (a) Each authorized provider of Postage Evidencing Systems must... custody and control of Postage Evidencing Systems and must specifically authorize in writing the proposed...

NMR Based Sensors for In Situ Monitoring of Changes in Groundwater Chemistry

DTIC Science & Technology

2017-04-21

herein to any specific commercial product, process, or service by trade name, trademark, manufacturer , or otherwise, does not necessarily constitute or...relaxation sensor employed in the field would need to be calibrated against a non- contaminated water sample taken from the same source, and... contaminants may prove more fruitful. For example, the original development of these sensors was aimed at detecting trace concentrations of specific

A system-of-systems modeling methodology for strategic general aviation design decision-making

NASA Astrophysics Data System (ADS)

Won, Henry Thome

General aviation has long been studied as a means of providing an on-demand "personal air vehicle" that bypasses the traffic at major commercial hubs. This thesis continues this research through development of a system of systems modeling methodology applicable to the selection of synergistic product concepts, market segments, and business models. From the perspective of the conceptual design engineer, the design and selection of future general aviation aircraft is complicated by the definition of constraints and requirements, and the tradeoffs among performance and cost aspects. Qualitative problem definition methods have been utilized, although their accuracy in determining specific requirement and metric values is uncertain. In industry, customers are surveyed, and business plans are created through a lengthy, iterative process. In recent years, techniques have developed for predicting the characteristics of US travel demand based on travel mode attributes, such as door-to-door time and ticket price. As of yet, these models treat the contributing systems---aircraft manufacturers and service providers---as independently variable assumptions. In this research, a methodology is developed which seeks to build a strategic design decision making environment through the construction of a system of systems model. The demonstrated implementation brings together models of the aircraft and manufacturer, the service provider, and most importantly the travel demand. Thus represented is the behavior of the consumers and the reactive behavior of the suppliers---the manufacturers and transportation service providers---in a common modeling framework. The results indicate an ability to guide the design process---specifically the selection of design requirements---through the optimization of "capability" metrics. Additionally, results indicate the ability to find synergetic solutions, that is solutions in which two systems might collaborate to achieve a better result than acting independently. Implementation of this methodology can afford engineers a more autonomous perspective in the concept exploration process, providing dynamic feedback about a design's potential success in specific market segments. The method also has potential to strengthen the connection between design and business departments, as well as between manufacturers, service providers, and infrastructure planners---bringing information about how the respective systems interact, and what might be done to improve synergism of systems.

Development of Integrated Programs for Aerospace-vehicle Design (IPAD): Product manufacture interactions with the design process

NASA Technical Reports Server (NTRS)

Crowell, H. A.

1979-01-01

The product manufacturing interactions with the design process and the IPAD requirements to support the interactions are described. The data requirements supplied to manufacturing by design are identified and quantified. Trends in computer-aided manufacturing are discussed and the manufacturing process of the 1980's is anticipated.

Prevention of Salmonella cross-contamination in an oilmeal manufacturing plant.

PubMed

Morita, T; Kitazawa, H; Iida, T; Kamata, S

2006-08-01

The mechanisms of Salmonella contamination in an oilmeal plant were investigated and the basic data were collected in order to achieve control of Salmonella in oilmeal. Salmonella was detected in all contamination vectors and environmental factors investigated, namely: operators, processing floor, dust in the air and rodents. In particular, high concentrations of Salmonella were detected on the processing floor of the manufacturing area, which has high oil content. Steam was the most effective disinfection method used for the processing floor, as the effects of heat sterilization and disinfection may work in tandem. In addition, restricting the movement of operators of the production chain remarkably reduced Salmonella contamination, even in areas of otherwise high contamination. Within the oilmeal plant, high Salmonella contamination rates for the processing floor represent the greatest risk of contamination of oilmeal via operators, dust in the air and rodents. Therefore, control of the processing floor is the most important means for reducing the oilmeal contamination rate. Specific Salmonella control methods for oilmeal plants have been established.

40 CFR 761.193 - Maintenance of monitoring records by persons who import, manufacture, process, distribute in...

Code of Federal Regulations, 2013 CFR

2013-07-01

... persons who import, manufacture, process, distribute in commerce, or use chemicals containing... records by persons who import, manufacture, process, distribute in commerce, or use chemicals containing inadvertently generated PCBs. (a) Persons who import, manufacture, process, distribute in commerce, or use...

40 CFR 761.193 - Maintenance of monitoring records by persons who import, manufacture, process, distribute in...

Code of Federal Regulations, 2011 CFR

2011-07-01

... persons who import, manufacture, process, distribute in commerce, or use chemicals containing... records by persons who import, manufacture, process, distribute in commerce, or use chemicals containing inadvertently generated PCBs. (a) Persons who import, manufacture, process, distribute in commerce, or use...

40 CFR 761.193 - Maintenance of monitoring records by persons who import, manufacture, process, distribute in...

Code of Federal Regulations, 2012 CFR

2012-07-01

... persons who import, manufacture, process, distribute in commerce, or use chemicals containing... records by persons who import, manufacture, process, distribute in commerce, or use chemicals containing inadvertently generated PCBs. (a) Persons who import, manufacture, process, distribute in commerce, or use...

40 CFR 761.193 - Maintenance of monitoring records by persons who import, manufacture, process, distribute in...

Code of Federal Regulations, 2014 CFR

2014-07-01

... persons who import, manufacture, process, distribute in commerce, or use chemicals containing... records by persons who import, manufacture, process, distribute in commerce, or use chemicals containing inadvertently generated PCBs. (a) Persons who import, manufacture, process, distribute in commerce, or use...

Innovative applications of artificial intelligence

NASA Astrophysics Data System (ADS)

Schorr, Herbert; Rappaport, Alain

Papers concerning applications of artificial intelligence are presented, covering applications in aerospace technology, banking and finance, biotechnology, emergency services, law, media planning, music, the military, operations management, personnel management, retail packaging, and manufacturing assembly and design. Specific topics include Space Shuttle telemetry monitoring, an intelligent training system for Space Shuttle flight controllers, an expert system for the diagnostics of manufacturing equipment, a logistics management system, a cooling systems design assistant, and a knowledge-based integrated circuit design critic. Additional topics include a hydraulic circuit design assistant, the use of a connector assembly specification expert system to harness detailed assembly process knowledge, a mixed initiative approach to airlift planning, naval battle management decision aids, an inventory simulation tool, a peptide synthesis expert system, and a system for planning the discharging and loading of container ships.

Dedication file preparation for commercial-grade electric components

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hendricks, J.R.; Farwell, C.R. Jr.

1988-01-01

Dedication is the process of making a commercial-grade item into a basic component that can be installed in safety systems. This process ensures that the commercially manufactured items are of the same or equivalent form, fit, function, and materials as the originally provided safety item. This process must ensure that the original utility's equipment qualification program is maintained per licensing commitments to 10CFR50.49 and general design criterion No. 4. Today, utilities recognize the need for establishing a dedication program to provide the flexibility in obtaining replacement items directly from the original manufacturers. This need has arisen because (a) most systemmore » houses, large manufacturers, and component manufacturers will sell their products only through distributors as straight commercial-grade items or only service former clients, and (b) lack of competition for specific safety-related items has resulted in excessive hardware cost and very long delivery schedules, which could affect plant availability. The vehicle for utilities to obtain safety-related items is to establish and manage a comprehensive dedication program for their own use or provide the direction for a nuclear supplier to follow. This paper provides both utilities and nuclear suppliers insight into the complexities of a dedication program. This insight is provided from our experience as a utilities agent and as a third-party nuclear supplier.« less

Development of advanced therapies in Italy: Management models and sustainability in six Italian cell factories.

PubMed

Gaipa, Giuseppe; Introna, Martino; Golay, Josee; Nolli, Maria Luisa; Vallanti, Giuliana; Parati, Eugenio; Giordano, Rosaria; Romagnoli, Luca; Melazzini, Mario; Biondi, Andrea; Biagi, Ettore

2016-04-01

On November 10, 2014, the representatives of all six certified Good Manufacturing Practices (GMP) cell factories operating in the Lombardy Region of Italy convened a 1-day workshop in Milan titled "Management Models for the Development And Sustainability of Cell Factories: Public-Private Partnership?" The speakers and panelists addressed not only the many scientific, technological and cultural challenges faced by Lombardy Cell Factories, but also the potential impact of advanced therapy medicinal products (ATMPs) on public health and the role played by translational research in this process. Future perspectives for research and development (R&D) and manufacturing processes in the field of regenerative medicine were discussed as well. This report summarizes the most important issues raised by the workshop participants with particular emphasis on strengths and limitations of the R&D and manufacturing processes for innovative therapeutics in Lombardy and what can be improved in this context while maintaining GMP standards. The participants highlighted several strategies to translate patient-specific advanced therapeutics into scaled manufacturing products for clinical application. These included (i) the development of a synergistic interaction between public and private institutions, (ii) better integration with Italian regulatory agencies and (iii) the creation of a network among Lombardy cell factories and other Italian and European institutions. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

In Situ Enhancement of Anaerobic Microbial Dechlorination of Polychlorinated Dibenzo-p-dioxins and Dibenzofurans in Marine and Estuarine Sediments

DTIC Science & Technology

2006-12-18

Defense. Reference herein to any specific commercial product, process , or service by trade name, trademark, manufacturer, or otherwise, does not...result of a combination of both respiratory and cometabolic processes . For in situ bioremediation, it would be most desirable to stimulate...conditions we examined. While the process has much potential, a key aspect of the technology – the nature and capability of the intrinsic microbial

A platform for European CMOS image sensors for space applications

NASA Astrophysics Data System (ADS)

Minoglou, K.; San Segundo Bello, D.; Sabuncuoglu Tezcan, D.; Haspeslagh, L.; Van Olmen, J.; Merry, B.; Cavaco, C.; Mazzamuto, F.; Toqué-Trésonne, I.; Moirin, R.; Brouwer, M.; Toccafondi, M.; Preti, G.; Rosmeulen, M.; De Moor, P.

2017-11-01

Both ESA and the EC have identified the need for a supply chain of CMOS imagers for space applications which uses solely European sources. An essential requirement on this supply chain is the platformization of the process modules, in particular when it comes to very specific processing steps, such as those required for the manufacturing of backside illuminated image sensors. This is the goal of the European (EC/FP7/SPACE) funded project EUROCIS. All EUROCIS partners have excellent know-how and track record in the expertise fields required. Imec has been leading the imager chip design and the front side and backside processing. LASSE, as a major player in the laser annealing supplier sector, has been focusing on the optimization of the process related to the backside passivation of the image sensors. TNO, known worldwide as a top developer of instruments for scientific research, including space research and sensors for satellites, has contributed in the domain of optical layers for space instruments and optimized antireflective coatings. Finally, Selex ES, as a world-wide leader for manufacturing instruments with expertise in various space missions and programs, has defined the image sensor specifications and is taking care of the final device characterization. In this paper, an overview of the process flow, the results on test structures and imagers processed using this platform will be presented.

The Automated Array Assembly Task of the Low-cost Silicon Solar Array Project, Phase 2

NASA Technical Reports Server (NTRS)

Coleman, M. G.; Grenon, L.; Pastirik, E. M.; Pryor, R. A.; Sparks, T. G.

1978-01-01

An advanced process sequence for manufacturing high efficiency solar cells and modules in a cost-effective manner is discussed. Emphasis is on process simplicity and minimizing consumed materials. The process sequence incorporates texture etching, plasma processes for damage removal and patterning, ion implantation, low pressure silicon nitride deposition, and plated metal. A reliable module design is presented. Specific process step developments are given. A detailed cost analysis was performed to indicate future areas of fruitful cost reduction effort. Recommendations for advanced investigations are included.

Silicon Valley's Processing Needs versus San Jose State University's Manufacturing Systems Processing Component: Implications for Industrial Technology

ERIC Educational Resources Information Center

Obi, Samuel C.

2004-01-01

Manufacturing professionals within universities tend to view manufacturing systems from a global perspective. This perspective tends to assume that manufacturing processes are employed equally in every manufacturing enterprise, irrespective of the geography and the needs of the people in those diverse regions. But in reality local and societal…

Printed polymer photonic devices for optical interconnect systems

NASA Astrophysics Data System (ADS)

Subbaraman, Harish; Pan, Zeyu; Zhang, Cheng; Li, Qiaochu; Guo, L. J.; Chen, Ray T.

2016-03-01

Polymer photonic device fabrication usually relies on the utilization of clean-room processes, including photolithography, e-beam lithography, reactive ion etching (RIE) and lift-off methods etc, which are expensive and are limited to areas as large as a wafer. Utilizing a novel and a scalable printing process involving ink-jet printing and imprinting, we have fabricated polymer based photonic interconnect components, such as electro-optic polymer based modulators and ring resonator switches, and thermo-optic polymer switch based delay networks and demonstrated their operation. Specifically, a modulator operating at 15MHz and a 2-bit delay network providing up to 35.4ps are presented. In this paper, we also discuss the manufacturing challenges that need to be overcome in order to make roll-to-roll manufacturing practically viable. We discuss a few manufacturing challenges, such as inspection and quality control, registration, and web control, that need to be overcome in order to realize true implementation of roll-to-roll manufacturing of flexible polymer photonic systems. We have overcome these challenges, and currently utilizing our inhouse developed hardware and software tools, <10μm alignment accuracy at a 5m/min is demonstrated. Such a scalable roll-to-roll manufacturing scheme will enable the development of unique optoelectronic devices which can be used in a myriad of different applications, including communication, sensing, medicine, security, imaging, energy, lighting etc.

21 CFR 201.122 - Drugs for processing, repacking, or manufacturing.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Drugs for processing, repacking, or manufacturing... for processing, repacking, or manufacturing. A drug in a bulk package, except tablets, capsules, or... manufacturing, processing, or repacking”; and if in substantially all dosage forms in which it may be dispensed...

The presence of Enterococcus, coliforms and E. coli in a commercial yeast manufacturing process.

PubMed

O'Brien, S S; Lindsay, D; von Holy, A

2004-07-01

This study evaluated a typical commercial yeast manufacturing process for bacterial contamination. Product line samples of a commercial yeast manufacturing process and the corresponding seed yeast manufacturing process were obtained upstream from the final compressed and dry yeast products. All samples were analysed before (non-PI) and after preliminary incubation (PI) at 37 degrees C for 24 h. The PI procedure was incorporated for amplification of bacterial counts below the lower detection limit. Enterococcus, coliform and Escherichia coli counts were quantified by standard pour-plate techniques using selective media. Presence at all stages and progressive increases in counts of Enterococcus, coliforms and E. coli during processing in the commercial manufacturing operation suggested that the primary source of contamination of both compressed and dry yeast with these bacteria was the seed yeast manufacturing process and that contamination was amplified throughout the commercial yeast manufacturing process. This was confirmed by surveys of the seed yeast manufacturing process which indicated that contamination of the seed yeast with Enterococcus, coliforms and E. coli occurred during scale up of seed yeast biomass destined as inoculum for the commercial fermentation.

47 CFR 301.5 - Manufacturers' technical approval process.

Code of Federal Regulations, 2010 CFR

2010-10-01

... intent to NTIA at least three months prior to submitting test results and sample models of converter... shall treat the notices of intent received as business confidential and proprietary information and will.... (d) Each model proposed to be a CECB shall meet the performance specification and features set forth...

13 CFR 125.5 - Certificate of Competency Program.

Code of Federal Regulations, 2010 CFR

2010-01-01

... the type of product being procured or the specific contract at issue. (iv) A non-manufacturer making... application. (1) The COC review process is not limited to the areas of nonresponsibility cited by the contracting officer. SBA may, at its discretion, independently evaluate the COC applicant for all elements of...

21 CFR 600.11 - Physical establishment, equipment, animals, and care.

Code of Federal Regulations, 2013 CFR

2013-04-01

... of 170 °C maintained for 2 hours with dry heat. Processing and storage containers, filters, filling... “Caution: microbial spores. See directions for storage, use and disposition.”, and (v) the container of... or product dedicated items from the manufacturing area. Environmental monitoring specific for the...

The hydroentanglement system of producing nonwoven fabrics of certain specific attributes and functionalities

USDA-ARS?s Scientific Manuscript database

Although the traditional technologies and processes of producing fabric structures, via yarn spinning, weaving, knitting, lacing, tufting, or the like, continue to be the ‘major league’ players in textile manufacturing today, the modern hydroentanglement system, commonly known as “spunlacing,” has a...

14 CFR 43.3 - Persons authorized to perform maintenance, preventive maintenance, rebuilding, and alterations.

Code of Federal Regulations, 2014 CFR

2014-01-01

... category. (h) Notwithstanding the provisions of paragraph (g) of this section, the Administrator may... Product and Process Specification issued by the Administrator; and (3) Perform any inspection required by... manufactures under a production certificate. (k) Updates of databases in installed avionics meeting the...

76 FR 8362 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-14

..., Glass Manufacturing and Secondary Nonferrous Metals Processing Area Sources (Renewal) AGENCY... for Clay Ceramics Manufacturing, Glass Manufacturing and Secondary Nonferrous Metals Processing Area..., glass manufacturing, and secondary nonferrous metals processing area sources. Estimated Number of...

The yeast stands alone: the future of protein biologic production.

PubMed

Love, Kerry R; Dalvie, Neil C; Love, J Christopher

2017-12-22

Yeasts are promising alternative hosts for the manufacturing of recombinant protein therapeutics because they simply and efficiently meet needs for both platform and small-market drugs. Fast accumulation of biomass and low-cost media reduce the cost-of-goods when using yeast, which in turn can enable agile, small-volume manufacturing facilities. Small, tractable yeast genomes are amenable to rapid process development, facilitating strain and product quality by design. Specifically, Pichia pastoris is becoming a widely accepted yeast for biopharmaceutical manufacturing in much of the world owing to a clean secreted product and the rapidly expanding understanding of its cell biology as a host organism. We advocate for a near term partnership spanning industry and academia to promote open source, timely development of yeast hosts. Copyright © 2017. Published by Elsevier Ltd.

Thin EFG octagons

NASA Astrophysics Data System (ADS)

Kalejs, J. P.

1994-03-01

This report describes work to advance the manufacturing line capabilities in crystal growth and laser cutting of Mobil Solar's unique edge-defined film-fed growth (EFG) octagon technology and to reduce the manufacturing costs of 10 cm x 10 cm polycrystalline silicon EFG wafers. The report summarizes the significant technical improvements in EFG technology achieved in the first 6 months of the PVMaT Phase 2 and the success in meeting program milestones. Technical results are reported for each of the three main pregrain areas: Task 5 -- Thin octagon growth (crystal growth) to reduce the thickness of the octagon to 200 microns; Task 6 -- Laser cutting-to improve the laser cutting process so as to produce wafers with decreased laser cutting damage at increased wafer throughput rates; and Task 7 -- Process control and product specification to implement advanced strategies in crystal growth process control and productivity designed to increase wafer yields.

Optical Coherence Tomography Enabling Non Destructive Metrology of Layered Polymeric GRIN Material

PubMed Central

Meemon, Panomsak; Yao, Jianing; Lee, Kye-Sung; Thompson, Kevin P.; Ponting, Michael; Baer, Eric; Rolland, Jannick P.

2013-01-01

Gradient Refractive INdex (GRIN) optical components have historically fallen short of theoretical expectations. A recent breakthrough is the manufacturing of nanolayered spherical GRIN (S-GRIN) polymer optical elements, where the construction method yields refractive index gradients that exceed 0.08. Here we report on the application of optical coherence tomography (OCT), including micron-class axial and lateral resolution advances, as effective, innovative methods for performing nondestructive diagnostic metrology on S-GRIN. We show that OCT can be used to visualize and quantify characteristics of the material throughout the manufacturing process. Specifically, internal film structure may be revealed and data are processed to extract sub-surface profiles of each internal film of the material to quantify 3D film thickness and homogeneity. The technique provides direct feedback into the fabrication process directed at optimizing the quality of the nanolayered S-GRIN polymer optical components.

Additive-manufactured patient-specific titanium templates for thoracic pedicle screw placement: novel design with reduced contact area.

PubMed

Takemoto, Mitsuru; Fujibayashi, Shunsuke; Ota, Eigo; Otsuki, Bungo; Kimura, Hiroaki; Sakamoto, Takeshi; Kawai, Toshiyuki; Futami, Tohru; Sasaki, Kiyoyuki; Matsushita, Tomiharu; Nakamura, Takashi; Neo, Masashi; Matsuda, Shuich

2016-06-01

Image-based navigational patient-specific templates (PSTs) for pedicle screw (PS) placement have been described. With recent advances in three-dimensional computer-aided designs and additive manufacturing technology, various PST designs have been reported, although the template designs were not optimized. We have developed a novel PST design that reduces the contact area without sacrificing stability. It avoids susceptibility to intervening soft tissue, template geometric inaccuracy, and difficulty during template fitting. Fourteen candidate locations on the posterior aspect of the vertebra were evaluated. Among them, locations that had high reproducibility on computed tomography (CT) images and facilitated accurate PS placement were selected for the final PST design. An additive manufacturing machine (EOSINT M270) fabricated the PSTs using commercially pure titanium powder. For the clinical study, 36 scoliosis patients and 4 patients with ossification of the posterior longitudinal ligament (OPLL) were treated with thoracic PSs using our newly developed PSTs. We intraoperatively and postoperatively evaluated the accuracy of the PS hole created by the PST. Based on the segmentation reproducibility and stability analyses, we selected seven small, round contact points for our PST: bilateral superior and inferior points on the transverse process base, bilateral inferior points on the laminar, and a superior point on the spinous process. Clinically, the success rates of PS placement using this PST design were 98.6 % (414/420) for scoliosis patients and 100 % (46/46) for OPLL patients. This study provides a useful design concept for the development and introduction of patient-specific navigational templates for placing PSs.

Simulating the Composite Propellant Manufacturing Process

NASA Technical Reports Server (NTRS)

Williamson, Suzanne; Love, Gregory

2000-01-01

There is a strategic interest in understanding how the propellant manufacturing process contributes to military capabilities outside the United States. The paper will discuss how system dynamics (SD) has been applied to rapidly assess the capabilities and vulnerabilities of a specific composite propellant production complex. These facilities produce a commonly used solid propellant with military applications. The authors will explain how an SD model can be configured to match a specific production facility followed by a series of scenarios designed to analyze operational vulnerabilities. By using the simulation model to rapidly analyze operational risks, the analyst gains a better understanding of production complexities. There are several benefits of developing SD models to simulate chemical production. SD is an effective tool for characterizing complex problems, especially the production process where the cascading effect of outages quickly taxes common understanding. By programming expert knowledge into an SD application, these tools are transformed into a knowledge management resource that facilitates rapid learning without requiring years of experience in production operations. It also permits the analyst to rapidly respond to crisis situations and other time-sensitive missions. Most importantly, the quantitative understanding gained from applying the SD model lends itself to strategic analysis and planning.

A new roadmap for biopharmaceutical drug product development: Integrating development, validation, and quality by design.

PubMed

Martin-Moe, Sheryl; Lim, Fredric J; Wong, Rita L; Sreedhara, Alavattam; Sundaram, Jagannathan; Sane, Samir U

2011-08-01

Quality by design (QbD) is a science- and risk-based approach to drug product development. Although pharmaceutical companies have historically used many of the same principles during development, this knowledge was not always formally captured or proactively submitted to regulators. In recent years, the US Food and Drug Administration has also recognized the need for more controls in the drug manufacturing processes, especially for biological therapeutics, and it has recently launched an initiative for Pharmaceutical Quality for the 21st Century to modernize pharmaceutical manufacturing and improve product quality. In the biopharmaceutical world, the QbD efforts have been mainly focused on active pharmaceutical ingredient processes with little emphasis on drug product development. We present a systematic approach to biopharmaceutical drug product development using a monoclonal antibody as an example. The approach presented herein leverages scientific understanding of products and processes, risk assessments, and rational experimental design to deliver processes that are consistent with QbD philosophy without excessive incremental effort. Data generated using these approaches will not only strengthen data packages to support specifications and manufacturing ranges but hopefully simplify implementation of postapproval changes. We anticipate that this approach will positively impact cost for companies, regulatory agencies, and patients, alike. Copyright © 2011 Wiley-Liss, Inc.

Ion beam figuring of silicon aspheres

NASA Astrophysics Data System (ADS)

Demmler, Marcel; Zeuner, Michael; Luca, Alfonz; Dunger, Thoralf; Rost, Dirk; Kiontke, Sven; Krüger, Marcus

2011-03-01

Silicon lenses are widely used for infrared applications. Especially for portable devices the size and weight of the optical system are very important factors. The use of aspherical silicon lenses instead of spherical silicon lenses results in a significant reduction of weight and size. The manufacture of silicon lenses is more challenging than the manufacture of standard glass lenses. Typically conventional methods like diamond turning, grinding and polishing are used. However, due to the high hardness of silicon, diamond turning is very difficult and requires a lot of experience. To achieve surfaces of a high quality a polishing step is mandatory within the manufacturing process. Nevertheless, the required surface form accuracy cannot be achieved through the use of conventional polishing methods because of the unpredictable behavior of the polishing tools, which leads to an unstable removal rate. To overcome these disadvantages a method called Ion Beam Figuring can be used to manufacture silicon lenses with high surface form accuracies. The general advantage of the Ion Beam Figuring technology is a contactless polishing process without any aging effects of the tool. Due to this an excellent stability of the removal rate without any mechanical surface damage is achieved. The related physical process - called sputtering - can be applied to any material and is therefore also applicable to materials of high hardness like Silicon (SiC, WC). The process is realized through the commercially available ion beam figuring system IonScan 3D. During the process, the substrate is moved in front of a focused broad ion beam. The local milling rate is controlled via a modulated velocity profile, which is calculated specifically for each surface topology in order to mill the material at the associated positions to the target geometry. The authors will present aspherical silicon lenses with very high surface form accuracies compared to conventionally manufactured lenses.

OAO battery data analysis

NASA Technical Reports Server (NTRS)

Gaston, S.; Wertheim, M.; Orourke, J. A.

1973-01-01

Summary, consolidation and analysis of specifications, manufacturing process and test controls, and performance results for OAO-2 and OAO-3 lot 20 Amp-Hr sealed nickel cadmium cells and batteries are reported. Correlation of improvements in control requirements with performance is a key feature. Updates for a cell/battery computer model to improve performance prediction capability are included. Applicability of regression analysis computer techniques to relate process controls to performance is checked.

Equipment and Analytical Companies Meeting Continuous Challenges May 20-21 2014 Continuous Manufacturing Symposium.

PubMed

Page, Trevor; Dubina, Henry; Fillipi, Gabriele; Guidat, Roland; Patnaik, Saroj; Poechlauer, Peter; Shering, Phil; Guinn, Martin; Mcdonnell, Peter; Johnston, Craig

2015-03-01

This white paper focuses on equipment, and analytical manufacturers' perspectives, regarding the challenges of continuous pharmaceutical manufacturing across five prompt questions. In addition to valued input from several vendors, commentary was provided from experienced pharmaceutical representatives, who have installed various continuous platforms. Additionally, a small medium enterprise (SME) perspective was obtained through interviews. A range of technical challenges is outlined, including: the presence of particles, equipment scalability, fouling (and cleaning), technology derisking, specific analytical challenges, and the general requirement of improved technical training. Equipment and analytical companies can make a significant contribution to help the introduction of continuous technology. A key point is that many of these challenges exist in batch processing and are not specific to continuous processing. Backward compatibility of software is not a continuous issue per se. In many cases, there is available learning from other industries. Business models and opportunities through outsourced development partners are also highlighted. Agile smaller companies and academic groups have a key role to play in developing skills, working collaboratively in partnerships, and focusing on solving relevant industry challenges. The precompetitive space differs for vendor companies compared with large pharmaceuticals. Currently, there is no strong consensus around a dominant continuous design, partly because of business dynamics and commercial interests. A more structured common approach to process design and hardware and software standardization would be beneficial, with initial practical steps in modeling. Conclusions include a digestible systems approach, accessible and published business cases, and increased user, academic, and supplier collaboration. This mirrors US FDA direction. The concept of silos in pharmaceutical companies is a common theme throughout the white papers. In the equipment domain, this is equally prevalent among a broad range of companies, mainly focusing on discrete areas. As an example, the flow chemistry and secondary drug product communities are almost entirely disconnected. Control and Process Analytical Technologies (PAT) companies are active in both domains. The equipment actors are a very diverse group with a few major Original Equipment Manufacturers (OEM) players and a variety of SME, project providers, integrators, upstream downstream providers, and specialist PAT. In some cases, partnerships or alliances are formed to increase critical mass. This white paper has focused on small molecules; equipment associated with biopharmaceuticals is covered in a separate white paper. More specifics on equipment detail are provided in final dosage form and drug substance white papers. The equipment and analytical development from laboratory to pilot to production is important, with a variety of sensors and complexity reducing with scale. The importance of robust processing rather than overcomplex control strategy mitigation is important. A search of nonacademic literature highlights, with a few notable exceptions, a relative paucity of material. Much focuses on the economics and benefits of continuous, rather than specifics of equipment issues. The disruptive nature of continuous manufacturing represents either an opportunity or a threat for many companies, so the incentive to change equipment varies. Also, for many companies, the pharmaceutical sector is not actually the dominant sector in terms of sales. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Equipment and analytical companies meeting continuous challenges. May 20-21, 2014 Continuous Manufacturing Symposium.

PubMed

Page, Trevor; Dubina, Henry; Fillipi, Gabriele; Guidat, Roland; Patnaik, Saroj; Poechlauer, Peter; Shering, Phil; Guinn, Martin; Mcdonnell, Peter; Johnston, Craig

2015-03-01

This white paper focuses on equipment, and analytical manufacturers' perspectives, regarding the challenges of continuous pharmaceutical manufacturing across five prompt questions. In addition to valued input from several vendors, commentary was provided from experienced pharmaceutical representatives, who have installed various continuous platforms. Additionally, a small medium enterprise (SME) perspective was obtained through interviews. A range of technical challenges is outlined, including: the presence of particles, equipment scalability, fouling (and cleaning), technology derisking, specific analytical challenges, and the general requirement of improved technical training. Equipment and analytical companies can make a significant contribution to help the introduction of continuous technology. A key point is that many of these challenges exist in batch processing and are not specific to continuous processing. Backward compatibility of software is not a continuous issue per se. In many cases, there is available learning from other industries. Business models and opportunities through outsourced development partners are also highlighted. Agile smaller companies and academic groups have a key role to play in developing skills, working collaboratively in partnerships, and focusing on solving relevant industry challenges. The precompetitive space differs for vendor companies compared with large pharmaceuticals. Currently, there is no strong consensus around a dominant continuous design, partly because of business dynamics and commercial interests. A more structured common approach to process design and hardware and software standardization would be beneficial, with initial practical steps in modeling. Conclusions include a digestible systems approach, accessible and published business cases, and increased user, academic, and supplier collaboration. This mirrors US FDA direction. The concept of silos in pharmaceutical companies is a common theme throughout the white papers. In the equipment domain, this is equally prevalent among a broad range of companies, mainly focusing on discrete areas. As an example, the flow chemistry and secondary drug product communities are almost entirely disconnected. Control and Process Analytical Technologies (PAT) companies are active in both domains. The equipment actors are a very diverse group with a few major Original Equipment Manufacturers (OEM) players and a variety of SME, project providers, integrators, upstream downstream providers, and specialist PAT. In some cases, partnerships or alliances are formed to increase critical mass. This white paper has focused on small molecules; equipment associated with biopharmaceuticals is covered in a separate white paper. More specifics on equipment detail are provided in final dosage form and drug substance white papers. The equipment and analytical development from laboratory to pilot to production is important, with a variety of sensors and complexity reducing with scale. The importance of robust processing rather than overcomplex control strategy mitigation is important. A search of nonacademic literature highlights, with a few notable exceptions, a relative paucity of material. Much focuses on the economics and benefits of continuous, rather than specifics of equipment issues. The disruptive nature of continuous manufacturing represents either an opportunity or a threat for many companies, so the incentive to change equipment varies. Also, for many companies, the pharmaceutical sector is not actually the dominant sector in terms of sales. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Concepts for the development of nanoscale stable precipitation-strengthened steels manufactured by conventional methods

DOE PAGES

Yablinsky, C. A.; Tippey, K. E.; Vaynman, S.; ...

2014-11-11

In this study, the development of oxide dispersion strengthened ferrous alloys has shown that microstructures designed for excellent irradiation resistance and thermal stability ideally contain stable nanoscale precipitates and dislocation sinks. Based upon this understanding, the microstructures of conventionally manufactured ferritic and ferritic-martensitic steels can be designed to include controlled volume fractions of fine, stable precipitates and dislocation sinks via specific alloying and processing paths. The concepts proposed here are categorized as advanced high-Cr ferritic-martensitic (AHCr-FM) and novel tailored precipitate ferritic (TPF) steels, which have the potential to improve the in-reactor performance of conventionally manufactured alloys. AHCr-FM steels have modifiedmore » alloy content relative to current reactor materials (such as alloy NF616/P92) to maximize desirable precipitates and control phase stability. TPF steels are designed to incorporate nickel aluminides, in addition to microalloy carbides, in a ferritic matrix to produce fine precipitate arrays with good thermal stability. Both alloying concepts may also benefit from thermomechanical processing to establish dislocation sinks and modify phase transformation behaviors. Alloying and processing paths toward designed microstructures are discussed for both AHCr-FM and TPF material classes.« less

Gaining the Competitive Edge: Design for Manufacturing

NASA Technical Reports Server (NTRS)

Batill, Stephen M.; Pinkelman, Jim; Sellar, Richard

1993-01-01

The successful design of a commercial aircraft which is intended to be in direct competition with existing aircraft requires a market analysis to establish design requirements, the development of a concept to achieve those goals. and the ability to economically manufacture the aircraft. It is often the case that an engineer designs system components with only the perspective of a particular discipline. The relationship of that component to the entire system is often a minor consideration. In an effort to highlight the interaction that is necessary during the design process, the students were organized into design/build teams and required to integrate aspects of market analysis, engineering design, production and economics into their concepts. In order to facilitate this process a hypothetical "Aeroworld" was established. Having been furnished relevant demographic and economic data for "Aeroworld". students were given the task of designing and building an aircraft for a specific market while achieving an economically competitive design. Involvement of the team in the evolution of the design from market definition to technical development to manufacturing allowed the students to identify critical issues in the design process and to encounter many of the conflicting requirements which arise in an aerospace systems design.

High speed micromachining with high power UV laser

NASA Astrophysics Data System (ADS)

Patel, Rajesh S.; Bovatsek, James M.

2013-03-01

Increasing demand for creating fine features with high accuracy in manufacturing of electronic mobile devices has fueled growth for lasers in manufacturing. High power, high repetition rate ultraviolet (UV) lasers provide an opportunity to implement a cost effective high quality, high throughput micromachining process in a 24/7 manufacturing environment. The energy available per pulse and the pulse repetition frequency (PRF) of diode pumped solid state (DPSS) nanosecond UV lasers have increased steadily over the years. Efficient use of the available energy from a laser is important to generate accurate fine features at a high speed with high quality. To achieve maximum material removal and minimal thermal damage for any laser micromachining application, use of the optimal process parameters including energy density or fluence (J/cm2), pulse width, and repetition rate is important. In this study we present a new high power, high PRF QuasarR 355-40 laser from Spectra-Physics with TimeShiftTM technology for unique software adjustable pulse width, pulse splitting, and pulse shaping capabilities. The benefits of these features for micromachining include improved throughput and quality. Specific example and results of silicon scribing are described to demonstrate the processing benefits of the Quasar's available power, PRF, and TimeShift technology.

A Process Management System for Networked Manufacturing

NASA Astrophysics Data System (ADS)

Liu, Tingting; Wang, Huifen; Liu, Linyan

With the development of computer, communication and network, networked manufacturing has become one of the main manufacturing paradigms in the 21st century. Under the networked manufacturing environment, there exist a large number of cooperative tasks susceptible to alterations, conflicts caused by resources and problems of cost and quality. This increases the complexity of administration. Process management is a technology used to design, enact, control, and analyze networked manufacturing processes. It supports efficient execution, effective management, conflict resolution, cost containment and quality control. In this paper we propose an integrated process management system for networked manufacturing. Requirements of process management are analyzed and architecture of the system is presented. And a process model considering process cost and quality is developed. Finally a case study is provided to explain how the system runs efficiently.

Engineering of the institutionalization of the circular economy at the level of casting production

NASA Astrophysics Data System (ADS)

Vescan, M. M.; Soporan, V. F.; Crișan, D. M.; Lehene, T. R.; Pădurețu, S.; Samuila, V.

2017-06-01

This paper is motivated by the necessity of introducing the principles of circular economy at the level of different social - economic activities, and from this point of view one of the fields with a special potential is that of the manufacture of castings. Objective: to connect to the organizing and application of the methodology of the circular economy principles. The proposed method is an innovating one, being connected to the use of institutionalization engineering. Formulating the subject: The subject formulated to be solved aims at the introduction of new approaches, defined through institutionalization engineering, which proposes to set the correlation of actions between the specifics of the circular economy and the specific elements of the manufacture of castings. Research method: An institutional structuring operation was imposed for the optimization of the research method, in which different versions interact at the following levels: the level of public policies, the level of the regulatory framework, the level of technical solutions and the level of financing solutions and financial instruments. The determination of the optimal solution established in a dynamic context, favorable for the requirements of the different actors present within the process, appeals to the elements of critical thinking, specific for the engineer’s actions. Achievement of the research activity: The research activity structures a methodology of quantifying the contributions of each stage of the manufacturing process for castings at the fulfilling of the specific conditions of the circular economy, indicating the critical areas of action for more efficient actions of the circular economy, according to the market economy requirements, where there is a potential of implementing the technical solutions by quantizing the financial solutions and the opportunity of using the financial instruments. The major contribution of the research: The proposed methodology, with examples at the level of castings manufacture, sets the bases of a new field of action of the engineering thinking, namely, that of circular economy institutionalization functioning. Conclusions of the research activity: The proposed methodology represents the bases of establishing a new instrument of action at the level of institutionalized functioning of the circular economy.

Changes in Consumer Attitudes toward Broad-Based and Environment-Specific Sodium Policies-SummerStyles 2012 and 2015.

PubMed

Odom, Erika C; Whittick, Corine; Tong, Xin; John, Katherine A; Cogswell, Mary E

2017-08-04

We examined temporal changes in consumer attitudes toward broad-based actions and environment-specific policies to limit sodium in restaurants, manufactured foods, and school and workplace cafeterias from the 2012 and 2015 SummerStyle surveys. We used two online, national research panel surveys to conduct a cross-sectional analysis of 7845 U.S. adults. Measures included self-reported agreement with broad-based actions and environment-specific policies to limit sodium in restaurants, manufactured foods, school cafeterias, workplace cafeterias, and quick-serve restaurants. Wald Chi-square tests were used to examine the difference between the two survey years and multivariate logistic regression was used to obtain odds ratios. Agreement with broad-based actions to limit sodium in restaurants (45.9% agreed in 2015) and manufactured foods (56.5% agreed in 2015) did not change between 2012 and 2015. From 2012 to 2015, there was a significant increase in respondents that supported environment-specific policies to lower sodium in school cafeterias (80.0% to 84.9%; p < 0.0001), workplace cafeterias (71.2% to 76.6%; p < 0.0001), and quick-serve restaurants (70.8% to 76.7%; p < 0.0001). Results suggest substantial agreement and support for actions to limit sodium in commercially-processed and prepared foods since 2012, with most consumers ready for actions to lower sodium in foods served in schools, workplaces, and quick-serve restaurants.

Changes in Consumer Attitudes toward Broad-Based and Environment-Specific Sodium Policies—SummerStyles 2012 and 2015

PubMed Central

Odom, Erika C.; Whittick, Corine; Tong, Xin; Cogswell, Mary E.

2017-01-01

We examined temporal changes in consumer attitudes toward broad-based actions and environment-specific policies to limit sodium in restaurants, manufactured foods, and school and workplace cafeterias from the 2012 and 2015 SummerStyle surveys. We used two online, national research panel surveys to conduct a cross-sectional analysis of 7845 U.S. adults. Measures included self-reported agreement with broad-based actions and environment-specific policies to limit sodium in restaurants, manufactured foods, school cafeterias, workplace cafeterias, and quick-serve restaurants. Wald Chi-square tests were used to examine the difference between the two survey years and multivariate logistic regression was used to obtain odds ratios. Agreement with broad-based actions to limit sodium in restaurants (45.9% agreed in 2015) and manufactured foods (56.5% agreed in 2015) did not change between 2012 and 2015. From 2012 to 2015, there was a significant increase in respondents that supported environment-specific policies to lower sodium in school cafeterias (80.0% to 84.9%; p < 0.0001), workplace cafeterias (71.2% to 76.6%; p < 0.0001), and quick-serve restaurants (70.8% to 76.7%; p < 0.0001). Results suggest substantial agreement and support for actions to limit sodium in commercially-processed and prepared foods since 2012, with most consumers ready for actions to lower sodium in foods served in schools, workplaces, and quick-serve restaurants. PMID:28777339

Laser pattern generator challenges in airborne molecular contamination protection

NASA Astrophysics Data System (ADS)

Ekberg, Mats; Skotte, Per-Uno; Utterback, Tomas; Paul, Swaraj; Kishkovich, Oleg P.; Hudzik, James S.

2003-08-01

The introduction of photomask laser pattern generators presents new challenges to system designers and manufacturers. One of the laser pattern generator's environmental operating challenges is Airborne Molecular Contamination (AMC), which affects both chemically amplified resists (CAResist) and laser optics. Similar challenges in CAResist protection have already been addressed in semiconductor wafer lithography with reasonable solutions and experience gained by all those involved. However, photomask and photomask equipment manufacturers have not previously had a comparable experience, and some photomask AMC issues differ from those seen in semiconductor wafer lithography. Culminating years of AMC experience, the authors discuss specific requirements of Photomask AMC. Air sampling and material of construction analysis were performed to understand these particular AMC challenges and used to develop an appropriate filtration specification for different classes of contaminates. The authors portray the importance of cooperation between tool designers and AMC experts early in the design stage to assure goal attainment to maximize both process stability and machine productivity in advanced mask making. In conclusion, the authors provide valuable recommendations to both laser tool users and other equipment manufacturers.

Use of gases in dairy manufacturing: A review.

PubMed

Adhikari, Bhaskar Mani; Truong, Tuyen; Bansal, Nidhi; Bhandari, Bhesh

2017-06-13

Use of gases (air, carbon dioxide and nitrogen) has been practiced in the manufacture of dairy products (i.e., ice cream, whipped cream and butter) to improve their texture, mouthfeel and shelf-life extension. Many attempts have also been made to incorporate other gases such as hydrogen, nitrous oxide, argon, xenon, and helium into the dairy systems for various product functionalities such as whipping, foaming, texture, aroma enhancement, and therapeutic properties. The gases can be dissolved in aqueous and fat phases or remain in the form of bubbles stabilized by protein or fat particles. The gas addition or infusion processes are typically simple and have been used commercially. This review focuses on the use of various gases in relation to their individually physical properties along with their specific roles in manufacturing and controlling quality of dairy products. It also recaps on how gases are included in the dairy systems. The information is important in understanding of addition of specific gas(es) into food systems, particularly dairy products, that potentially provide intervention opportunities for modifying and/or creating innovative food structures and functionalities.

Standardization of rate of sugar addition for the manufacture of Thabdi.

PubMed

Hirpara, Krupa B; Patel, H G; Prajapati, J P

2015-02-01

Traditional Indian Dairy Products are manufactured in India using an age old practice which varies from place to place. For manufacture of these products industrially, a standard formulation is required. Thabdi, a region specific, very popular heat desiccated milk product is one of such products which has not been studied scientifically. Sugar plays an important role in physico-chemical, sensory, textural characteristics and also the shelf life of any milk sweet. Hence for process standardization of Thabdi manufacture, different levels of sugar i.e. 4, 6, 8 and 10 (percent of milk) were studied so that an optimum level yielding best organoleptic characteristics in final product can be selected. The product was made from milk standardized to 0.66 Fat:SNF level and added with ghee @ 1.2 % of milk at the time of colour and texture development stage as selected from the earlier phase of study. Based on the results obtained, a level of 8 % sugar addition on the milk basis at the time of manufacture has been selected to have full taste and sensory attributes.

Selective Laser Melting: a regular unit cell approach for the manufacture of porous, titanium, bone in-growth constructs, suitable for orthopedic applications.

PubMed

Mullen, Lewis; Stamp, Robin C; Brooks, Wesley K; Jones, Eric; Sutcliffe, Christopher J

2009-05-01

In this study, a novel porous titanium structure for the purpose of bone in-growth has been designed, manufactured and evaluated. The structure was produced by Selective Laser Melting (SLM); a rapid manufacturing process capable of producing highly intricate, functionally graded parts. The technique described utilizes an approach based on a defined regular unit cell to design and produce structures with a large range of both physical and mechanical properties. These properties can be tailored to suit specific requirements; in particular, functionally graded structures with bone in-growth surfaces exhibiting properties comparable to those of human bone have been manufactured. The structures were manufactured and characterized by unit cell size, strand diameter, porosity, and compression strength. They exhibited a porosity (10-95%) dependant compression strength (0.5-350 Mpa) comparable to the typical naturally occurring range. It is also demonstrated that optimized structures have been produced that possesses ideal qualities for bone in-growth applications and that these structures can be applied in the production of orthopedic devices. (c) 2008 Wiley Periodicals, Inc.

Space manufacturing III; Proceedings of the Fourth Conference, Princeton University, Princeton, N.J., May 14-17, 1979

NASA Technical Reports Server (NTRS)

Grey, J. (Editor); Krop, C.

1979-01-01

Papers are presented on the various technological, political, economic, environmental and social aspects of large manufacturing facilities in space. Specific topics include the potential global market for satellite solar power stations in 2025, the electrostatic separation of lunar soil, methods for extraterrestrial materials processing, the socio-political status of efforts toward the development of space manufacturing facilities, the financing of space industrialization, the optimization of space manufacturing systems, the design and project status of Mass Driver Two, and the use of laser-boosted lighter-than-air-vehicles as heavy-lift launch vehicles. Attention is also given to systems integration in the development of controlled ecological life support systems, the design of a space manufacturing facility to use lunar materials, high performance solar sails, the environmental effects of the satellite power system reference design, the guidance, trajectory and capture of lunar materials ejected from the moon by mass driver, the relative design merits of zero-gravity and one-gravity space environments, consciousness alteration in space and the prospecting and retrieval of asteroids.

Polylactides in additive biomanufacturing.

PubMed

Poh, Patrina S P; Chhaya, Mohit P; Wunner, Felix M; De-Juan-Pardo, Elena M; Schilling, Arndt F; Schantz, Jan-Thorsten; van Griensven, Martijn; Hutmacher, Dietmar W

2016-12-15

New advanced manufacturing technologies under the alias of additive biomanufacturing allow the design and fabrication of a range of products from pre-operative models, cutting guides and medical devices to scaffolds. The process of printing in 3 dimensions of cells, extracellular matrix (ECM) and biomaterials (bioinks, powders, etc.) to generate in vitro and/or in vivo tissue analogue structures has been termed bioprinting. To further advance in additive biomanufacturing, there are many aspects that we can learn from the wider additive manufacturing (AM) industry, which have progressed tremendously since its introduction into the manufacturing sector. First, this review gives an overview of additive manufacturing and both industry and academia efforts in addressing specific challenges in the AM technologies to drive toward AM-enabled industrial revolution. After which, considerations of poly(lactides) as a biomaterial in additive biomanufacturing are discussed. Challenges in wider additive biomanufacturing field are discussed in terms of (a) biomaterials; (b) computer-aided design, engineering and manufacturing; (c) AM and additive biomanufacturing printers hardware; and (d) system integration. Finally, the outlook for additive biomanufacturing was discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Space manufacturing facilities: Space colonies; Proceedings of the Princeton Conference, Princeton University, Princeton, N.J., May 7-9, 1975

NASA Technical Reports Server (NTRS)

Grey, J.

1977-01-01

Reports submitted to the conference encompass: administration and law relating to inhabited space facilities and colonies; space manufacturing and processing; organization and construction of space habitats and management of space colony farms; winning and acquisition of lunar and asteroidal materials for sustaining autonomous space colonies. Attention is given to trajectories between earth, low earth orbit, earth-moon libration points (specifically L5), circumlunar parking orbits, and trajectories in translunar space; effects of low gravity and zero gravity on human physiology and on materials processing; architecture and landscaping for space colonies; closed ecosystems of space colonies. Varieties of human cultures and value hierarchies around the earth are examined for broader perspectives on the social organization of space colonies.

A carbon dioxide stripping model for mammalian cell culture in manufacturing scale bioreactors.

PubMed

Xing, Zizhuo; Lewis, Amanda M; Borys, Michael C; Li, Zheng Jian

2017-06-01

Control of carbon dioxide within the optimum range is important in mammalian bioprocesses at the manufacturing scale in order to ensure robust cell growth, high protein yields, and consistent quality attributes. The majority of bioprocess development work is done in laboratory bioreactors, in which carbon dioxide levels are more easily controlled. Some challenges in carbon dioxide control can present themselves when cell culture processes are scaled up, because carbon dioxide accumulation is a common feature due to longer gas-residence time of mammalian cell culture in large scale bioreactors. A carbon dioxide stripping model can be used to better understand and optimize parameters that are critical to cell culture processes at the manufacturing scale. The prevailing carbon dioxide stripping models in literature depend on mass transfer coefficients and were applicable to cell culture processes with low cell density or at stationary/cell death phase. However, it was reported that gas bubbles are saturated with carbon dioxide before leaving the culture, which makes carbon dioxide stripping no longer depend on a mass transfer coefficient in the new generation cell culture processes characterized by longer exponential growth phase, higher peak viable cell densities, and higher specific production rate. Here, we present a new carbon dioxide stripping model for manufacturing scale bioreactors, which is independent of carbon dioxide mass transfer coefficient, but takes into account the gas-residence time and gas CO 2 saturation time. The model was verified by CHO cell culture processes with different peak viable cell densities (7 to 12 × 10 6  cells mL -1 ) for two products in 5,000-L and 25,000-L bioreactors. The model was also applied to a next generation cell culture process to optimize cell culture conditions and reduce carbon dioxide levels at manufacturing scale. The model provides a useful tool to understand and better control cell culture carbon dioxide profiles for process development, scale up, and characterization. Biotechnol. Bioeng. 2017;114: 1184-1194. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Recent Advances in Near-Net-Shape Fabrication of Al-Li Alloy 2195 for Launch Vehicles

NASA Technical Reports Server (NTRS)

Wagner, John; Domack, Marcia; Hoffman, Eric

2007-01-01

Recent applications in launch vehicles use 2195 processed to Super Lightweight Tank specifications. Potential benefits exist by tailoring heat treatment and other processing parameters to the application. Assess the potential benefits and advocate application of Al-Li near-net-shape technologies for other launch vehicle structural components. Work with manufacturing and material producers to optimize Al-Li ingot shape and size for enhanced near-net-shape processing. Examine time dependent properties of 2195 critical for reusable applications.

Weld Wire Investigation Summary

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cunningham, M.A.

1999-03-22

After GTA welding reservoir A production/process prove-in assemblies, X-ray examination detected a lack of sidewall fusion. After examining several possible causes, it was determined that the weld wire filler metal was responsible, particularly the wire cleaning process. The final conclusion was that the filler wire must be abrasively cleaned in a particular manner to perform as required. The abrasive process was incorporated into the wire material specification, ensuring consistency for all reservoir GTA welding at AlliedSignal Federal Manufacturing and Technologies (FM and T).

Use of Process Improvement Tools in Radiology.

PubMed

Rawson, James V; Kannan, Amogha; Furman, Melissa

2016-01-01

Process improvement techniques are common in manufacturing and industry. Over the past few decades these principles have been slowly introduced in select health care settings. This article reviews the Plan, Do, Study, and Act cycle, Six Sigma, the System of Profound Knowledge, Lean, and the theory of constraints. Specific process improvement tools in health care and radiology are presented in the order the radiologist is likely to encounter them in an improvement project. Copyright © 2015 Mosby, Inc. All rights reserved.

Implementation of Statistical Process Control: Evaluating the Mechanical Performance of a Candidate Silicone Elastomer Docking Seal

NASA Technical Reports Server (NTRS)

Oravec, Heather Ann; Daniels, Christopher C.

2014-01-01

The National Aeronautics and Space Administration has been developing a novel docking system to meet the requirements of future exploration missions to low-Earth orbit and beyond. A dynamic gas pressure seal is located at the main interface between the active and passive mating components of the new docking system. This seal is designed to operate in the harsh space environment, but is also to perform within strict loading requirements while maintaining an acceptable level of leak rate. In this study, a candidate silicone elastomer seal was designed, and multiple subscale test articles were manufactured for evaluation purposes. The force required to fully compress each test article at room temperature was quantified and found to be below the maximum allowable load for the docking system. However, a significant amount of scatter was observed in the test results. Due to the stochastic nature of the mechanical performance of this candidate docking seal, a statistical process control technique was implemented to isolate unusual compression behavior from typical mechanical performance. The results of this statistical analysis indicated a lack of process control, suggesting a variation in the manufacturing phase of the process. Further investigation revealed that changes in the manufacturing molding process had occurred which may have influenced the mechanical performance of the seal. This knowledge improves the chance of this and future space seals to satisfy or exceed design specifications.

Latent structure analysis of the process variables and pharmaceutical responses of an orally disintegrating tablet.

PubMed

Hayashi, Yoshihiro; Oshima, Etsuko; Maeda, Jin; Onuki, Yoshinori; Obata, Yasuko; Takayama, Kozo

2012-01-01

A multivariate statistical technique was applied to the design of an orally disintegrating tablet and to clarify the causal correlation among variables of the manufacturing process and pharmaceutical responses. Orally disintegrating tablets (ODTs) composed mainly of mannitol were prepared via the wet-granulation method using crystal transition from the δ to the β form of mannitol. Process parameters (water amounts (X(1)), kneading time (X(2)), compression force (X(3)), and amounts of magnesium stearate (X(4))) were optimized using a nonlinear response surface method (RSM) incorporating a thin plate spline interpolation (RSM-S). The results of a verification study revealed that the experimental responses, such as tensile strength and disintegration time, coincided well with the predictions. A latent structure analysis of the pharmaceutical formulations of the tablet performed using a Bayesian network led to the clear visualization of a causal connection among variables of the manufacturing process and tablet characteristics. The quantity of β-mannitol in the granules (Q(β)) was affected by X(2) and influenced all granule properties. The specific surface area of the granules was affected by X(1) and Q(β) and had an effect on all tablet characteristics. Moreover, the causal relationships among the variables were clarified by inferring conditional probability distributions. These techniques provide a better understanding of the complicated latent structure among variables of the manufacturing process and tablet characteristics.

Harnessing the Potential of Additive Manufacturing

DTIC Science & Technology

2016-12-01

manufacturing age, which is dominated by standards for materials, processes and process control. Conventional manufacturing is based upon a design that is...documented either in a drawing or a computer-aided design (CAD) file. The manufacturing team then develops a docu- mented public or private process for...31 Defense AT&L: November-December 2016 Harnessing the Potential of Additive Manufacturing Bill Decker Decker is director of Technology

CMV-specific T cell isolation from G-CSF mobilized peripheral blood: depletion of myeloid progenitors eliminates non-specific binding of MHC-multimers.

PubMed

Beloki, Lorea; Ciaurriz, Miriam; Mansilla, Cristina; Zabalza, Amaya; Perez-Valderrama, Estela; Samuel, Edward R; Lowdell, Mark W; Ramirez, Natalia; Olavarria, Eduardo

2014-11-19

Cytomegalovirus (CMV)-specific T cell infusion to immunocompromised patients following allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) is able to induce a successful anti-viral response. These cells have classically been manufactured from steady-state apheresis samples collected from the donor in an additional harvest prior to G-CSF mobilization, treatment that induces hematopoietic stem cell (HSC) mobilization to the periphery. However, two closely-timed cellular collections are not usually available in the unrelated donor setting, which limits the accessibility of anti-viral cells for adoptive immunotherapy. CMV-specific cytotoxic T cell (CTL) manufacture from the same G-CSF mobilized donor stem cell harvest offers great regulatory advantages, but the isolation using MHC-multimers is hampered by the high non-specific binding to myeloid progenitors, which reduces the purity of the cellular product. In the present study we describe an easy and fast method based on plastic adherence to remove myeloid cell subsets from 11 G-CSF mobilized donor samples. CMV-specific CTLs were isolated from the non-adherent fraction using pentamers and purity and yield of the process were compared to products obtained from unmanipulated samples. After the elimination of unwanted cell subtypes, non-specific binding of pentamers was notably reduced. Accordingly, following the isolation process the purity of the obtained cellular product was significantly improved. G-CSF mobilized leukapheresis samples can successfully be used to isolate antigen-specific T cells with MHC-multimers to be adoptively transferred following allo-HSCT, widening the accessibility of this therapy in the unrelated donor setting. The combination of the clinically translatable plastic adherence process to the antigen-specific cell isolation using MHC-multimers improves the quality of the therapeutic cellular product, thereby reducing the clinical negative effects associated with undesired alloreactive cell infusion.

Identified research directions for using manufacturing knowledge earlier in the product lifecycle

PubMed Central

Hedberg, Thomas D.; Hartman, Nathan W.; Rosche, Phil; Fischer, Kevin

2016-01-01

Design for Manufacturing (DFM), especially the use of manufacturing knowledge to support design decisions, has received attention in the academic domain. However, industry practice has not been studied enough to provide solutions that are mature for industry. The current state of the art for DFM is often rule-based functionality within Computer-Aided Design (CAD) systems that enforce specific design requirements. That rule-based functionality may or may not dynamically affect geometry definition. And, if rule-based functionality exists in the CAD system, it is typically a customization on a case-by-case basis. Manufacturing knowledge is a phrase with vast meanings, which may include knowledge on the effects of material properties decisions, machine and process capabilities, or understanding the unintended consequences of design decisions on manufacturing. One of the DFM questions to answer is how can manufacturing knowledge, depending on its definition, be used earlier in the product lifecycle to enable a more collaborative development environment? This paper will discuss the results of a workshop on manufacturing knowledge that highlights several research questions needing more study. This paper proposes recommendations for investigating the relationship of manufacturing knowledge with shape, behavior, and context characteristics of product to produce a better understanding of what knowledge is most important. In addition, the proposal includes recommendations for investigating the system-level barriers to reusing manufacturing knowledge and how model-based manufacturing may ease the burden of knowledge sharing. Lastly, the proposal addresses the direction of future research for holistic solutions of using manufacturing knowledge earlier in the product lifecycle. PMID:27990027

Identified research directions for using manufacturing knowledge earlier in the product lifecycle.

PubMed

Hedberg, Thomas D; Hartman, Nathan W; Rosche, Phil; Fischer, Kevin

2017-01-01

Design for Manufacturing (DFM), especially the use of manufacturing knowledge to support design decisions, has received attention in the academic domain. However, industry practice has not been studied enough to provide solutions that are mature for industry. The current state of the art for DFM is often rule-based functionality within Computer-Aided Design (CAD) systems that enforce specific design requirements. That rule-based functionality may or may not dynamically affect geometry definition. And, if rule-based functionality exists in the CAD system, it is typically a customization on a case-by-case basis. Manufacturing knowledge is a phrase with vast meanings, which may include knowledge on the effects of material properties decisions, machine and process capabilities, or understanding the unintended consequences of design decisions on manufacturing. One of the DFM questions to answer is how can manufacturing knowledge, depending on its definition, be used earlier in the product lifecycle to enable a more collaborative development environment? This paper will discuss the results of a workshop on manufacturing knowledge that highlights several research questions needing more study. This paper proposes recommendations for investigating the relationship of manufacturing knowledge with shape, behavior, and context characteristics of product to produce a better understanding of what knowledge is most important. In addition, the proposal includes recommendations for investigating the system-level barriers to reusing manufacturing knowledge and how model-based manufacturing may ease the burden of knowledge sharing. Lastly, the proposal addresses the direction of future research for holistic solutions of using manufacturing knowledge earlier in the product lifecycle.

Supercritical fluid particle design for poorly water-soluble drugs (review).

PubMed

Sun, Yongda

2014-01-01

Supercritical fluid particle design (SCF PD) offers a number of routes to improve solubility and dissolution rate for enhancing the bioavailability of poorly water-soluble drugs, which can be adopted through an in-depth knowledge of SCF PD processes and the molecular properties of active pharmaceutical ingredients (API) and drug delivery system (DDS). Combining with research experiences in our laboratory, this review focuses on the most recent development of different routes (nano-micron particles, polymorphic particles, composite particles and bio-drug particles) to improve solubility and dissolution rate of poorly water-soluble drugs, covering the fundamental concept of SCF and the principle of SCF PD processes which are typically used to control particle size, shape, morphology and particle form and hence enable notable improvement in the dissolution rate of the poorly water-soluble drugs. The progress of the industrialization of SCF PD processes in pharmaceutical manufacturing environment with scaled-up plant under current good manufacturing process (GMP) specification is also considered in this review.

Modeling of Ti-W Solidification Microstructures Under Additive Manufacturing Conditions

NASA Astrophysics Data System (ADS)

Rolchigo, Matthew R.; Mendoza, Michael Y.; Samimi, Peyman; Brice, David A.; Martin, Brian; Collins, Peter C.; LeSar, Richard

2017-07-01

Additive manufacturing (AM) processes have many benefits for the fabrication of alloy parts, including the potential for greater microstructural control and targeted properties than traditional metallurgy processes. To accelerate utilization of this process to produce such parts, an effective computational modeling approach to identify the relationships between material and process parameters, microstructure, and part properties is essential. Development of such a model requires accounting for the many factors in play during this process, including laser absorption, material addition and melting, fluid flow, various modes of heat transport, and solidification. In this paper, we start with a more modest goal, to create a multiscale model for a specific AM process, Laser Engineered Net Shaping (LENS™), which couples a continuum-level description of a simplified beam melting problem (coupling heat absorption, heat transport, and fluid flow) with a Lattice Boltzmann-cellular automata (LB-CA) microscale model of combined fluid flow, solute transport, and solidification. We apply this model to a binary Ti-5.5 wt pct W alloy and compare calculated quantities, such as dendrite arm spacing, with experimental results reported in a companion paper.

76 FR 40052 - Regulatory Agenda

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-07

... Current Good Manufacturing 0910-AG10 Practice in Manufacturing, Processing, Packing or Holding Animal Food... in Manufacturing, Processing, Packing or Holding Animal Food Legal Authority: 21 U.S.C. 342; 21 U.S.C... constitute on farm manufacturing or processing of food that is not grown, raised, or consumed on a farm or...

A Roadmap for the Implementation of Continued Process Verification.

PubMed

Boyer, Marcus; Gampfer, Joerg; Zamamiri, Abdel; Payne, Robin

2016-01-01

In 2014, the members of the BioPhorum Operations Group (BPOG) produced a 100-page continued process verification case study, entitled "Continued Process Verification: An Industry Position Paper with Example Protocol". This case study captures the thought processes involved in creating a continued process verification plan for a new product in response to the U.S. Food and Drug Administration's guidance on the subject introduced in 2011. In so doing, it provided the specific example of a plan developed for a new molecular antibody product based on the "A MAb Case Study" that preceded it in 2009.This document provides a roadmap that draws on the content of the continued process verification case study to provide a step-by-step guide in a more accessible form, with reference to a process map of the product life cycle. It could be used as a basis for continued process verification implementation in a number of different scenarios: For a single product and process;For a single site;To assist in the sharing of data monitoring responsibilities among sites;To assist in establishing data monitoring agreements between a customer company and a contract manufacturing organization. The U.S. Food and Drug Administration issued guidance on the management of manufacturing processes designed to improve quality and control of drug products. This involved increased focus on regular monitoring of manufacturing processes, reporting of the results, and the taking of opportunities to improve. The guidance and practice associated with it is known as continued process verification This paper summarizes good practice in responding to continued process verification guidance, gathered from subject matter experts in the biopharmaceutical industry. © PDA, Inc. 2016.

EUV mask manufacturing readiness in the merchant mask industry

NASA Astrophysics Data System (ADS)

Green, Michael; Choi, Yohan; Ham, Young; Kamberian, Henry; Progler, Chris; Tseng, Shih-En; Chiou, Tsann-Bim; Miyazaki, Junji; Lammers, Ad; Chen, Alek

2017-10-01

As nodes progress into the 7nm and below regime, extreme ultraviolet lithography (EUVL) becomes critical for all industry participants interested in remaining at the leading edge. One key cost driver for EUV in the supply chain is the reflective EUV mask. As of today, the relatively few end users of EUV consist primarily of integrated device manufactures (IDMs) and foundries that have internal (captive) mask manufacturing capability. At the same time, strong and early participation in EUV by the merchant mask industry should bring value to these chip makers, aiding the wide-scale adoption of EUV in the future. For this, merchants need access to high quality, representative test vehicles to develop and validate their own processes. This business circumstance provides the motivation for merchants to form Joint Development Partnerships (JDPs) with IDMs, foundries, Original Equipment Manufacturers (OEMs) and other members of the EUV supplier ecosystem that leverage complementary strengths. In this paper, we will show how, through a collaborative supplier JDP model between a merchant and OEM, a novel, test chip driven strategy is applied to guide and validate mask level process development. We demonstrate how an EUV test vehicle (TV) is generated for mask process characterization in advance of receiving chip maker-specific designs. We utilize the TV to carry out mask process "stress testing" to define process boundary conditions which can be used to create Mask Rule Check (MRC) rules as well as serve as baseline conditions for future process improvement. We utilize Advanced Mask Characterization (AMC) techniques to understand process capability on designs of varying complexity that include EUV OPC models with and without sub-resolution assist features (SRAFs). Through these collaborations, we demonstrate ways to develop EUV processes and reduce implementation risks for eventual mass production. By reducing these risks, we hope to expand access to EUV mask capability for the broadest community possible as the technology is implemented first within and then beyond the initial early adopters.

Manufacturing Process Simulation of Large-Scale Cryotanks

NASA Technical Reports Server (NTRS)

Babai, Majid; Phillips, Steven; Griffin, Brian; Munafo, Paul M. (Technical Monitor)

2002-01-01

NASA's Space Launch Initiative (SLI) is an effort to research and develop the technologies needed to build a second-generation reusable launch vehicle. It is required that this new launch vehicle be 100 times safer and 10 times cheaper to operate than current launch vehicles. Part of the SLI includes the development of reusable composite and metallic cryotanks. The size of these reusable tanks is far greater than anything ever developed and exceeds the design limits of current manufacturing tools. Several design and manufacturing approaches have been formulated, but many factors must be weighed during the selection process. Among these factors are tooling reachability, cycle times, feasibility, and facility impacts. The manufacturing process simulation capabilities available at NASA's Marshall Space Flight Center have played a key role in down selecting between the various manufacturing approaches. By creating 3-D manufacturing process simulations, the varying approaches can be analyzed in a virtual world before any hardware or infrastructure is built. This analysis can detect and eliminate costly flaws in the various manufacturing approaches. The simulations check for collisions between devices, verify that design limits on joints are not exceeded, and provide cycle times which aid in the development of an optimized process flow. In addition, new ideas and concerns are often raised after seeing the visual representation of a manufacturing process flow. The output of the manufacturing process simulations allows for cost and safety comparisons to be performed between the various manufacturing approaches. This output helps determine which manufacturing process options reach the safety and cost goals of the SLI.

Empirical modeling for intelligent, real-time manufacture control

NASA Technical Reports Server (NTRS)

Xu, Xiaoshu

1994-01-01

Artificial neural systems (ANS), also known as neural networks, are an attempt to develop computer systems that emulate the neural reasoning behavior of biological neural systems (e.g. the human brain). As such, they are loosely based on biological neural networks. The ANS consists of a series of nodes (neurons) and weighted connections (axons) that, when presented with a specific input pattern, can associate specific output patterns. It is essentially a highly complex, nonlinear, mathematical relationship or transform. These constructs have two significant properties that have proven useful to the authors in signal processing and process modeling: noise tolerance and complex pattern recognition. Specifically, the authors have developed a new network learning algorithm that has resulted in the successful application of ANS's to high speed signal processing and to developing models of highly complex processes. Two of the applications, the Weld Bead Geometry Control System and the Welding Penetration Monitoring System, are discussed in the body of this paper.

Post-growth process for flexible CdS/CdTe thin film solar cells with high specific power.

PubMed

Cho, Eunwoo; Kang, Yoonmook; Kim, Donghwan; Kim, Jihyun

2016-05-16

We demonstrated a flexible CdS/CdTe thin film solar cell with high specific power of approximately 254 W/kg. A flexible and ultra-light weight CdS/CdTe cell treated with pre-NP etch process exhibited high conversion efficiency of 13.56% in superstrate configuration. Morphological, structural and optical changes of CdS/CdTe thin films were characterized when pre-NP etch step was incorporated to the conventional post-deposition process. Improvement of photovoltaic parameters can be attributed to the removal of the oxide and the formation of Te-rich layer, which benefit the activation process. Pre-NP etched cell maintained their flexibility and performance under the repeated tensile strain of 0.13%. Our method can pave a way for manufacturing flexible CdS/CdTe thin film solar cells with high specific power for mobile and aerospace applications.

19 CFR 191.8 - Specific manufacturing drawback ruling.

Code of Federal Regulations, 2014 CFR

2014-04-01

... favor of the parent corporation. (b) Sample application. Sample formats for applications for specific manufacturing drawback rulings are contained in appendix B to this part. (c) Content of application. The application of each manufacturer or producer shall include the following information as applicable: (1) Name...

19 CFR 191.8 - Specific manufacturing drawback ruling.

Code of Federal Regulations, 2011 CFR

2011-04-01

... favor of the parent corporation. (b) Sample application. Sample formats for applications for specific manufacturing drawback rulings are contained in appendix B to this part. (c) Content of application. The application of each manufacturer or producer shall include the following information as applicable: (1) Name...

19 CFR 191.8 - Specific manufacturing drawback ruling.

Code of Federal Regulations, 2013 CFR

2013-04-01

... favor of the parent corporation. (b) Sample application. Sample formats for applications for specific manufacturing drawback rulings are contained in appendix B to this part. (c) Content of application. The application of each manufacturer or producer shall include the following information as applicable: (1) Name...

19 CFR 191.8 - Specific manufacturing drawback ruling.

Code of Federal Regulations, 2012 CFR

2012-04-01

... favor of the parent corporation. (b) Sample application. Sample formats for applications for specific manufacturing drawback rulings are contained in appendix B to this part. (c) Content of application. The application of each manufacturer or producer shall include the following information as applicable: (1) Name...

3D additive manufactured 316L components microstructural features and changes induced by working life cycles

NASA Astrophysics Data System (ADS)

Pace, M. L.; Guarnaccio, A.; Dolce, P.; Mollica, D.; Parisi, G. P.; Lettino, A.; Medici, L.; Summa, V.; Ciancio, R.; Santagata, A.

2017-10-01

The ability of processing through laser beams different kinds of metallic powders for direct production of 3D components with complex geometries has been gaining an impressive and growing attention for specific industrial applications. The process which can be distinguished as Selective Laser Sintering or Selective Laser Melting is even considered, more generally, as Additive Manufacturing where layer by layer material is built by the interaction between a laser beam and a powder bed. The rapid heating of the powder due to the laser beam energy transfer process followed by a rapid cooling rate induces within the manufactured material a cellular structure with fine sub-grains, which are in the range of few hundreds of micrometers. These metastable structures, which are smaller than the grain size in conventionally manufactured 316L stainless steel components, can undertake towards a recrystallization process due to either heat or mechanical treatments. For instance, when sub-grain boundaries of the cells are enriched with Mo and higher concentration of dislocation, dynamical processes occur generating local residual stresses. In these circumstances the segregation of Mo in cell boundaries is out of thermodynamic equilibrium conditions so that microstructures and phases are metastable. In the range of 1100-1400 °C heat treatments a complete dissolution of Mo in the Fe matrix with a gradual disappearance of sub-microns cell is observed feeding the growth of larger austenitic sub-grains formation. It follows a higher degree of Mo dissolution in the material matrix and a decrease of dislocation's concentration (Saeidi et al., 2015) [1]. In the work here presented we point out which are the microstructural features of stainless steel 316L components realized by Additive Manufacturing. Furthermore, the occurrence of a microstructural evolution is presented after experiencing to fatigue of 80000 cycles some door joints obtained by this technique. A decrease of dislocation's number, an increase of twinning due to the growth of grains and to the release of local stresses can be hypothesized following that an important role could be played by the presence of dislocations in cell boundaries as well as oxides nano-inclusion formed in-situ during the Additive Manufacturing process (Saeidi et al., 2015) [2]. From these outcomes it is going to be presented how the 3D components produced by Additive Manufacturing could change and improve their features for potential industrial applications during life cycles and enhance such a behavior by taking carefully into account the laser parameters and its scanning speed.

Measurement and analysis of flow in 3D preforms for aerospace composites

NASA Astrophysics Data System (ADS)

Stewart, Andrew Lawrence

Composite materials have become viable alternatives to traditional engineering materials for many different product categories. Liquid transfer moulding (LTM) processes, specifically resin transfer moulding (RTM), is a cost-effective manufacturing technique for creating high performance composite parts. These parts can be tailor-made to their specific application by optimizing the properties of the textile preform. Preforms which require little or no further assembly work and are close to the shape of the final part are critical to obtaining high quality parts while simultaneously reducing labour and costs associated with other composite manufacturing techniques. One type of fabric which is well suited for near-net- shape preforms is stitched non-crimp fabrics. These fabrics offer very high in-plane strength and stiffness while also having increased resistance to delamination. Manufacturing parts from these dry preforms typically involves long-scale fluid flow through both open channels and porous fibre bundles. This thesis documents and analyzes the flow of fluid through preforms manufactured from non-crimp fabrics featuring through-thickness stitches. The objective of this research is to determine the effect of this type of stitch on the RTM injection process. All of the tests used preforms with fibre volume fractions representative of primary and secondary structural parts. A series of trials was conducted using different fibre materials, flow rates, fibre volumes fractions, and degrees of fibre consolidation. All of the trials were conducted for cases similar to RTM. Consolidation of the fibres showed improvements to both the thoroughness of the filling and to the fibre volume fraction. Experimentally determined permeability data was shown to trend well with simple models and precision of the permeability data was comparable to values presented by other authors who studied fabrics which did not feature the through-thickness stitches.

3D Printing, Additive Manufacturing, and Solid Freeform Fabrication: The Technologies of the Past, Present and Future

NASA Astrophysics Data System (ADS)

Beaman, Joseph

2015-03-01

Starting in the late 1980's, several new technologies were created that have the potential to revolutionize manufacturing. These technologies are, for the most part, additive processes that build up parts layer by layer. In addition, the processes that are being touted for hard-core manufacturing are primarily laser or e-beam based processes. This presentation gives a brief history of Additive Manufacturing and gives an assessment for these technologies. These technologies initially grew out of a commercial need for rapid prototyping. This market has a different requirement for process and quality control than traditional manufacturing. The relatively poor process control of the existing commercial Additive Manufacturing equipment is a vestige of this history. This presentation discusses this history and improvements in quality over time. The emphasis will be on Additive Manufacturing processes that are being considered for direct manufacturing, which is a different market than the 3D Printing ``Makerbot'' market. Topics discussed include past and present machine sensors, materials, and operational methods that were used in the past and those that are used today to create manufactured parts. Finally, a discussion of new methods and future directions of AM is presented.

Corroborating tomographic defect metrics with mechanical response in an additively manufactured precipitation-hardened stainless steel

NASA Astrophysics Data System (ADS)

Madison, Jonathan D.; Underwood, Olivia D.; Swiler, Laura P.; Boyce, Brad L.; Jared, Bradley H.; Rodelas, Jeff M.; Salzbrenner, Bradley C.

2018-04-01

The intrinsic relation between structure and performance is a foundational tenant of most all materials science investigations. While the specific form of this relation is dictated by material system, processing route and performance metric of interest, it is widely agreed that appropriate characterization of a material allows for greater accuracy in understanding and/or predicting material response. However, in the context of additive manufacturing, prior models and expectations of material performance must be revisited as performance often diverges from traditional values, even among well explored material systems. This work utilizes micro-computed tomography to quantify porosity and lack of fusion defects in an additively manufactured stainless steel and relates these metrics to performance across a statistically significant population using high-throughput mechanical testing. The degree to which performance in additively manufactured stainless steel can and cannot be correlated to detectable porosity will be presented and suggestions for performing similar experiments will be provided.

The integrated simulation and assessment of the impacts of process change in biotherapeutic antibody production.

PubMed

Chhatre, Sunil; Jones, Carl; Francis, Richard; O'Donovan, Kieran; Titchener-Hooker, Nigel; Newcombe, Anthony; Keshavarz-Moore, Eli

2006-01-01

Growing commercial pressures in the pharmaceutical industry are establishing a need for robust computer simulations of whole bioprocesses to allow rapid prediction of the effects of changes made to manufacturing operations. This paper presents an integrated process simulation that models the cGMP manufacture of the FDA-approved biotherapeutic CroFab, an IgG fragment used to treat rattlesnake envenomation (Protherics U.K. Limited, Blaenwaun, Ffostrasol, Llandysul, Wales, U.K.). Initially, the product is isolated from ovine serum by precipitation and centrifugation, before enzymatic digestion of the IgG to produce FAB and FC fragments. These are purified by ion exchange and affinity chromatography to remove the FC and non-specific FAB fragments from the final venom-specific FAB product. The model was constructed in a discrete event simulation environment and used to determine the potential impact of a series of changes to the process, such as increasing the step efficiencies or volumes of chromatographic matrices, upon product yields and process times. The study indicated that the overall FAB yield was particularly sensitive to changes in the digestive and affinity chromatographic step efficiencies, which have a predicted 30% greater impact on process FAB yield than do the precipitation or centrifugation stages. The study showed that increasing the volume of affinity matrix has a negligible impact upon total process time. Although results such as these would require experimental verification within the physical constraints of the process and the facility, the model predictions are still useful in allowing rapid "what-if" scenario analysis of the likely impacts of process changes within such an integrated production process.

Recommendations for designing and conducting cold-fill hold challenge studies for acidified food products

USDA-ARS?s Scientific Manuscript database

A scheduled process developed for manufacture of acidified foods must be validated with data from existing literature or from a product-specific challenge study, either of which can establish both safety and shelf stability. The challenge study would evaluate the ability of a particular food product...

Invasion, Alienation, and Imperialist Nostalgia: Overcoming the Necrophilous Nature of Neoliberal Schools

ERIC Educational Resources Information Center

Petrovic, John E.; Kuntz, Aaron M.

2018-01-01

The authors present a materialist analysis of the effects of neoliberalism in education. Specifically, they contend that neoliberalism is a form of cultural invasion that begets necrophilia. Neoliberalism is necrophilous in promoting a cultural desire to fix fluid systems and processes. Such desire manufactures both individuals known and…

49 CFR 178.36 - Specification 3A and 3AX seamless steel cylinders.

Code of Federal Regulations, 2012 CFR

2012-10-01

.... Cylinders must be manufactured using equipment and processes adequate to ensure that each cylinder produced... openings. Threads are required on openings. (1) Threads must be clean cut, even, without checks, and to gauge. (2) Taper threads, when used, must be of length not less than as specified for American Standard...

49 CFR 178.36 - Specification 3A and 3AX seamless steel cylinders.

Code of Federal Regulations, 2013 CFR

2013-10-01

.... Cylinders must be manufactured using equipment and processes adequate to ensure that each cylinder produced... openings. Threads are required on openings. (1) Threads must be clean cut, even, without checks, and to gauge. (2) Taper threads, when used, must be of length not less than as specified for American Standard...

49 CFR 178.36 - Specification 3A and 3AX seamless steel cylinders.

Code of Federal Regulations, 2014 CFR

2014-10-01

.... Cylinders must be manufactured using equipment and processes adequate to ensure that each cylinder produced... openings. Threads are required on openings. (1) Threads must be clean cut, even, without checks, and to gauge. (2) Taper threads, when used, must be of length not less than as specified for American Standard...

40 CFR 711.3 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... manufactured (including imported) or processed. Intended for use by children means the chemical substance or mixture is used in or on a product that is specifically intended for use by children age 14 or younger. A chemical substance or mixture is intended for use by children when the submitter answers “yes” to at least...

40 CFR 711.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... manufactured (including imported) or processed. Intended for use by children means the chemical substance or mixture is used in or on a product that is specifically intended for use by children age 14 or younger. A chemical substance or mixture is intended for use by children when the submitter answers “yes” to at least...

40 CFR 711.3 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... manufactured (including imported) or processed. Intended for use by children means the chemical substance or mixture is used in or on a product that is specifically intended for use by children age 14 or younger. A chemical substance or mixture is intended for use by children when the submitter answers “yes” to at least...

Computer-Related Success and Failure: A Longitudinal Field Study of the Factors Influencing Computer-Related Performance.

ERIC Educational Resources Information Center

Rozell, E. J.; Gardner, W. L., III

1999-01-01

A model of the intrapersonal processes impacting computer-related performance was tested using data from 75 manufacturing employees in a computer training course. Gender, computer experience, and attributional style were predictive of computer attitudes, which were in turn related to computer efficacy, task-specific performance expectations, and…

Equipment and Supplies For Collecting, Processing, Storing, and Testing Forest Tree Seed

Treesearch

F.T. Bonner

1977-01-01

This publication is a directory of information on equipment and supplies used in handling and treating tree seed. The use of each device is briefly described. Specifications such as size, capacity, or model number are given. Manufacturers' or suppliers' names are listed, and users of the equipment are identified.

High Temperature Thermoplastic Additive Manufacturing Using Low-Cost, Open-Source Hardware

NASA Technical Reports Server (NTRS)

Gardner, John M.; Stelter, Christopher J.; Yashin, Edward A.; Siochi, Emilie J.

2016-01-01

Additive manufacturing (or 3D printing) via Fused Filament Fabrication (FFF), also known as Fused Deposition Modeling (FDM), is a process where material is placed in specific locations layer-by-layer to create a complete part. Printers designed for FFF build parts by extruding a thermoplastic filament from a nozzle in a predetermined path. Originally developed for commercial printers, 3D printing via FFF has become accessible to a much larger community of users since the introduction of Reprap printers. These low-cost, desktop machines are typically used to print prototype parts or novelty items. As the adoption of desktop sized 3D printers broadens, there is increased demand for these machines to produce functional parts that can withstand harsher conditions such as high temperature and mechanical loads. Materials meeting these requirements tend to possess better mechanical properties and higher glass transition temperatures (Tg), thus requiring printers with high temperature printing capability. This report outlines the problems and solutions, and includes a detailed description of the machine design, printing parameters, and processes specific to high temperature thermoplastic 3D printing.

SOCMA study urges flexibility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kirschner, E.

In implementing the 1990 Pollution Prevention Act, regulators and legislators should hold off on cookie-cutter, numerical goal-based requirements to allow for site and process specific programs, says a study sponsored by the Synthetic Organic Chemicals Manufacturers Association (SOCMA; Washington). Companies should have that flexibility to target their resources toward those activities that reduce pollution cost effectively, says SOCMA environmental quality committee chairman Art Gillen, who is also BASF director of environmental regulatory affairs. The study - conducted by Woodward-Clyde Consultants (Denver) - examines four batch and custom chemical manufacturing films. As in the Clean Air Act, the batch processing ofmore » SOCMA-member plants should be considered in new regulations, Gillen says. For example, the study found that most wastes are from shutdowns and cleanouts, and there are frequent charges in waste streams and raw materials. Those characteristics do not lend themselves to annual reduction goals. Also, specific goals could have a wide range of costs: measures to reduce stack air emissions run from $18/lb to $1,106/lb. SOCMA says it will present the study to Congress and the Environmental Protection Agency.« less

Atmospheric Release Advisory Capability Pilot Project at Two Nuclear Power Plants and Associated State Offices of Emergency Preparedness.

DTIC Science & Technology

1983-01-01

assumes any legal liability or responsibility for the accuracy, comn- pleteness. or usefulness of any information, apparatus, product. or process ...disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial products, process , or service...by trade name, trademark, manufacturer, or otherwise, does not necessarily constitute or imply. its endorsement. recommendation, or favoring by the U

40 CFR 63.149 - Control requirements for certain liquid streams in open systems within a chemical manufacturing...

Code of Federal Regulations, 2010 CFR

2010-07-01

... streams in open systems within a chemical manufacturing process unit. 63.149 Section 63.149 Protection of... open systems within a chemical manufacturing process unit. (a) The owner or operator shall comply with... Air Pollutants From the Synthetic Organic Chemical Manufacturing Industry for Process Vents, Storage...

Concurrent use of magnetic bearings for rotor support and force sensing for the nondestructive evaluation of manufacturing processes

NASA Astrophysics Data System (ADS)

Kasarda, Mary; Imlach, Joseph; Balaji, P. A.; Marshall, Jeremy T.

2000-06-01

Active magnetic bearings are a proven technology in turbomachinery applications and they offer considerable promise for improving the performance of manufacturing processes. The Active Magnetic Bearing (AMB) is a feedback mechanism that supports a spinning shaft by levitating it in a magnetic field. AMBs have significantly higher surface speed capability than rolling element bearings and they eliminate the potential for product contamination by eliminating the requirement for bearing lubrication. In addition, one of the most promising capabilities for manufacturing applications is the ability of the AMB to act concurrently as both a support bearing and non-invasive force sensor. The feedback nature of the AMB allows for its use as a load cell to continuously measure shaft forces necessary for levitation based on information about the magnetic flux density in the air gaps. This measurement capability may be exploited to improve the process control of such products as textile fibers and photographic films where changes in shaft loads may indicate changes in product quality. This paper discusses the operation of AMBs and their potential benefits in manufacturing equipment along with results from research addressing accurate AMB force sensing performance in field applications. Specifically, results from the development of enhanced AMB measurement algorithms to better account for magnetic fringing and leakage effects to improve the accuracy of this technique are presented. Results from the development of a new on-line calibration procedure for robust in-situ calibration of AMBs in a field application such as a manufacturing plant scenario are also presented including results of Magnetic Finite Element Analysis (MFEA) verification of the procedure.

Boosting Manufacturing through Modular Chemical Process Intensification

ScienceCinema

None

2018-06-12

Manufacturing USA's Rapid Advancement in Process Intensification Deployment Institute will focus on developing breakthrough technologies to boost domestic energy productivity and energy efficiency by 20 percent in five years through manufacturing processes.

Boosting Manufacturing through Modular Chemical Process Intensification

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2016-12-09

Manufacturing USA's Rapid Advancement in Process Intensification Deployment Institute will focus on developing breakthrough technologies to boost domestic energy productivity and energy efficiency by 20 percent in five years through manufacturing processes.

WHO Expert Committee on Specifications for Pharmaceutical Preparations. Fiftieth report.

PubMed

2016-01-01

The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use. Good pharmacopoeial practices; FIP-WHO technical guidelines: points to consider in the provision by health-care professionals of children-specific preparations that are not available as authorized products; Guidance on good manufacturing practices for biological products; Guidance on good manufacturing practices: inspection report, including Appendix 1: Model inspection report; Guidance on good data and record management practices; Good trade and distribution practices for starting materials; Guidelines on the conduct of surveys of the quality of medicines; Collaborative procedure between the World Health Organization (WHO) prequalification team and national regulatory authorities in the assessment and accelerated national registration of WHO-prequalified pharmaceutical products and vaccines; Guidance for organizations performing in vivo bioequivalence studies; and World Health Organization (WHO) general guidance on variations to multisource pharmaceutical products.

Solid state laser applications in photovoltaics manufacturing

NASA Astrophysics Data System (ADS)

Dunsky, Corey; Colville, Finlay

2008-02-01

Photovoltaic energy conversion devices are on a rapidly accelerating growth path driven by increasing government and societal pressure to use renewable energy as part of an overall strategy to address global warming attributed to greenhouse gas emissions. Initially supported in several countries by generous tax subsidies, solar cell manufacturers are relentlessly pushing the performance/cost ratio of these devices in a quest to reach true cost parity with grid electricity. Clearly this eventual goal will result in further acceleration in the overall market growth. Silicon wafer based solar cells are currently the mainstay of solar end-user installations with a cost up to three times grid electricity. But next-generation technology in the form of thin-film devices promises streamlined, high-volume manufacturing and greatly reduced silicon consumption, resulting in dramatically lower per unit fabrication costs. Notwithstanding the modest conversion efficiency of thin-film devices compared to wafered silicon products (around 6-10% versus 15-20%), this cost reduction is driving existing and start-up solar manufacturers to switch to thin-film production. A key aspect of these devices is patterning large panels to create a monolithic array of series-interconnected cells to form a low current, high voltage module. This patterning is accomplished in three critical scribing processes called P1, P2, and P3. Lasers are the technology of choice for these processes, delivering the desired combination of high throughput and narrow, clean scribes. This paper examines these processes and discusses the optimization of industrial lasers to meet their specific needs.

Using Additive Manufacturing to Print a CubeSat Propulsion System

NASA Technical Reports Server (NTRS)

Marshall, William M.

2015-01-01

CubeSats are increasingly being utilized for missions traditionally ascribed to larger satellites CubeSat unit (1U) defined as 10 cm x 10 cm x 11 cm. Have been built up to 6U sizes. CubeSats are typically built up from commercially available off-the-shelf components, but have limited capabilities. By using additive manufacturing, mission specific capabilities (such as propulsion), can be built into a system. This effort is part of STMD Small Satellite program Printing the Complete CubeSat. Interest in propulsion concepts for CubeSats is rapidly gaining interest-Numerous concepts exist for CubeSat scale propulsion concepts. The focus of this effort is how to incorporate into structure using additive manufacturing. End-use of propulsion system dictates which type of system to develop-Pulse-mode RCS would require different system than a delta-V orbital maneuvering system. Team chose an RCS system based on available propulsion systems and feasibility of printing using a materials extrusion process. Initially investigated a cold-gas propulsion system for RCS applications-Materials extrusion process did not permit adequate sealing of part to make this a functional approach.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Plotkowski, A.; Rios, O.; Sridharan, N.

Our present research in metal additive manufacturing (AM) focuses on designing processing parameters around existing alloys designed for traditional manufacturing. However, to maximize the benefits of AM, alloys should be designed to specifically take advantage of the unique thermal conditions of these processes. Furthermore, our study focuses on the development of a design methodology for alloys in AM, using a newly developed Al-Ce alloy as an initial case study. To evaluate the candidacy of this system for fusion based additive manufacturing, single-line laser melts were made on cast Al-12Ce plates using three different beam velocities (100, 200, and 300 mm/min).more » The microstructure was evaluated in the as-melted and heat treated conditions (24 hrs at 300°C). An extremely fine microstructure was observed within the weld pools, evolving from eutectic at the outer solid-liquid boundaries to a primary Al FCC dendritic/cellular structure nearer the melt-pool centerline. We rationalized the observed microstructures through the construction of a microstructure selection map for the Al-Ce binary system, which will be used to enable future alloy design. Interestingly, the heat treated samples exhibited no microstructural coarsening.« less

Assessing your competitors' application of CIM/CIP. [Computer Integrated Manufacturing/Processing

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, M.J.; Evans, H.N.

1993-07-01

As part of the authors consulting assignments, they are frequently asked to describe what is best industry practice in the area of computer integrated manufacturing/processing (CIM/CIP). This might be specific to a particular piece, such as advanced controls or a laboratory system. Often it is in response to the enormous publicity given to CIM/CIP--begging the question, Who in the hydrocarbon industry is actually doing it '' Although much of this information is available to consultants, client confidentiality precludes its release. Instead, included is a questionnaire intended to be completed by representatives of manufacturing sites. The data gathered will be analyzedmore » and reported in a future issue. The intent is to give anyone who has completed the questionnaire the opportunity to assess the position of his or her site with respect to the competition. To show how this might work a prototype study was completed. This included an estimate of the advanced control benefits achieved in 68 refineries in Western Europe. So that sites could be compared, these were expressed as a percentage of the maximum economically achievable.« less

Standard cell electrical and physical variability analysis based on automatic physical measurement for design-for-manufacturing purposes

NASA Astrophysics Data System (ADS)

Shauly, Eitan; Parag, Allon; Khmaisy, Hafez; Krispil, Uri; Adan, Ofer; Levi, Shimon; Latinski, Sergey; Schwarzband, Ishai; Rotstein, Israel

2011-04-01

A fully automated system for process variability analysis of high density standard cell was developed. The system consists of layout analysis with device mapping: device type, location, configuration and more. The mapping step was created by a simple DRC run-set. This database was then used as an input for choosing locations for SEM images and for specific layout parameter extraction, used by SPICE simulation. This method was used to analyze large arrays of standard cell blocks, manufactured using Tower TS013LV (Low Voltage for high-speed applications) Platforms. Variability of different physical parameters like and like Lgate, Line-width-roughness and more as well as of electrical parameters like drive current (Ion), off current (Ioff) were calculated and statistically analyzed, in order to understand the variability root cause. Comparison between transistors having the same W/L but with different layout configurations and different layout environments (around the transistor) was made in terms of performances as well as process variability. We successfully defined "robust" and "less-robust" transistors configurations, and updated guidelines for Design-for-Manufacturing (DfM).

Multi-methodological investigation of the variability of the microstructure of HPMC hard capsules.

PubMed

Faulhammer, E; Kovalcik, A; Wahl, V; Markl, D; Stelzer, F; Lawrence, S; Khinast, J G; Paudel, A

2016-09-25

The objective of this study was to analyze differences in the subtle microstructure of three different grades of HMPC hard capsule shells using mechanical, spectroscopic, microscopic and tomographic approaches. Dynamic mechanical analysis (DMA), thermogravimetric analysis (TGA), vibrational spectroscopic, X-Ray scattering techniques as well as environmental scanning electron microscopy (ESEM) and optical coherence tomography (OCT) were used. Two HPMC capsules manufactured via chemical gelling, one capsule shell manufactured via thermal gelling and one thermally gelled transparent capsule were included. Characteristic micro-structural alterations (associated manufacturing processes) such as mechanical and physical properties relevant to capsule performance and processability were thoroughly elucidated with the integration of data obtained from multi-methodological investigations. The physico-chemical and physico-mechanical data obtained from a gamut of techniques implied that thermally gelled HPMC hard capsule shells could offer an advantage in terms of machinability during capsule filling, owing to their superior micro- and macroscopic structure as well as specifically the mechanical stability under dry or humid conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Modulating laser intensity profile ellipticity for microstructural control during metal additive manufacturing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roehling, Tien T.; Wu, Sheldon S. Q.; Khairallah, Saad A.

Additively manufactured (AM) metals are often highly textured, containing large columnar grains that initiate epitaxially under steep temperature gradients and rapid solidification conditions. These unique microstructures partially account for the massive property disparity existing between AM and conventionally processed alloys. Although equiaxed grains are desirable for isotropic mechanical behavior, the columnar-to-equiaxed transition remains difficult to predict for conventional solidification processes, and much more so for AM. In this study, the effects of laser intensity profile ellipticity on melt track macrostructures and microstructures were studied in 316L stainless steel. Experimental results were supported by temperature gradients and melt velocities simulated usingmore » the ALE3D multi-physics code. As a general trend, columnar grains preferentially formed with increasing laser power and scan speed for all beam profiles. However, when conduction mode laser heating occurs, scan parameters that result in coarse columnar microstructures using Gaussian profiles produce equiaxed or mixed equiaxed-columnar microstructures using elliptical profiles. Furthermore, by modulating spatial laser intensity profiles on the fly, site-specific microstructures and properties can be directly engineered into additively manufactured parts.« less

Modulating laser intensity profile ellipticity for microstructural control during metal additive manufacturing

DOE PAGES

Roehling, Tien T.; Wu, Sheldon S. Q.; Khairallah, Saad A.; ...

2017-02-12

Additively manufactured (AM) metals are often highly textured, containing large columnar grains that initiate epitaxially under steep temperature gradients and rapid solidification conditions. These unique microstructures partially account for the massive property disparity existing between AM and conventionally processed alloys. Although equiaxed grains are desirable for isotropic mechanical behavior, the columnar-to-equiaxed transition remains difficult to predict for conventional solidification processes, and much more so for AM. In this study, the effects of laser intensity profile ellipticity on melt track macrostructures and microstructures were studied in 316L stainless steel. Experimental results were supported by temperature gradients and melt velocities simulated usingmore » the ALE3D multi-physics code. As a general trend, columnar grains preferentially formed with increasing laser power and scan speed for all beam profiles. However, when conduction mode laser heating occurs, scan parameters that result in coarse columnar microstructures using Gaussian profiles produce equiaxed or mixed equiaxed-columnar microstructures using elliptical profiles. Furthermore, by modulating spatial laser intensity profiles on the fly, site-specific microstructures and properties can be directly engineered into additively manufactured parts.« less

Thermally sprayed prepregs for thixoforging of UD fiber reinforced light metal MMCs

NASA Astrophysics Data System (ADS)

Silber, Martin; Wenzelburger, Martin; Gadow, Rainer

2007-04-01

Low density and good mechanical properties are the basic requirements for lightweight structures in automotive and aerospace applications. With their high specific strength and strain to failure values, aluminum alloys could be used for such applications. Only the insufficient stiffness and thermal and fatigue strength prevented their usage in high-end applications. One possibility to solve this problem is to reinforce the light metal with unidirectional fibers. The UD fiber allows tailoring of the reinforcement to meet the direction of the component's load. In this study, the production of thermally sprayed prepregs for the manufacturing of continuous fiber reinforced MMC by thixoforging is analysed. The main aim is to optimize the winding procedure, which determines the fiber strand position and tension during the coating process. A method to wind and to coat the continuous fibers with an easy-to-use handling technique for the whole manufacturing process is presented. The prepregs were manufactured by producing arc wire sprayed AlSi6 coatings on fibers bundles. First results of bending experiments showed appropriate mechanical properties.

Continuous Manufacturing in Pharmaceutical Process Development and Manufacturing.

PubMed

Burcham, Christopher L; Florence, Alastair J; Johnson, Martin D

2018-06-07

The pharmaceutical industry has found new applications for the use of continuous processing for the manufacture of new therapies currently in development. The transformation has been encouraged by regulatory bodies as well as driven by cost reduction, decreased development cycles, access to new chemistries not practical in batch, improved safety, flexible manufacturing platforms, and improved product quality assurance. The transformation from batch to continuous manufacturing processing is the focus of this review. The review is limited to small, chemically synthesized organic molecules and encompasses the manufacture of both active pharmaceutical ingredients (APIs) and the subsequent drug product. Continuous drug product is currently used in approved processes. A few examples of production of APIs under current good manufacturing practice conditions using continuous processing steps have been published in the past five years, but they are lagging behind continuous drug product with respect to regulatory filings.

Potential of Continuous Manufacturing for Liposomal Drug Products.

PubMed

Worsham, Robert D; Thomas, Vaughan; Farid, Suzanne S

2018-05-21

Over the last several years, continuous manufacturing of pharmaceuticals has evolved from bulk APIs and solid oral dosages into the more complex realm of biologics. The development of continuous downstream processing techniques has allowed biologics manufacturing to realize the benefits (e.g. improved economics, more consistent quality) that come with continuous processing. If relevant processing techniques and principles are selected, the opportunity arises to develop continuous manufacturing designs for additional pharmaceutical products including liposomal drug formulations. Liposome manufacturing has some inherent aspects that make it favorable for a continuous process. Other aspects such as formulation refinement, materials of construction, and aseptic processing need development, but present an achievable challenge. This paper reviews the current state of continuous manufacturing technology applicable to liposomal drug product manufacturing and an assessment of the challenges and potential of this application. This article is protected by copyright. All rights reserved.

21 CFR 801.122 - Medical devices for processing, repacking, or manufacturing.

Code of Federal Regulations, 2010 CFR

2010-04-01

....122 Medical devices for processing, repacking, or manufacturing. A device intended for processing... act if its label bears the statement “Caution: For manufacturing, processing, or repacking”. ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Medical devices for processing, repacking, or...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lherbier, Louis, W.; Novotnak, David, J.; Herling, Darrell, R.

Hot forming processes such as forging, die casting and glass forming require tooling that is subjected to high temperatures during the manufacturing of components. Current tooling is adversely affected by prolonged exposure at high temperatures. Initial studies were conducted to determine the root cause of tool failures in a number of applications. Results show that tool failures vary and depend on the operating environment under which they are used. Major root cause failures include (1) thermal softening, (2) fatigue and (3) tool erosion, all of which are affected by process boundary conditions such as lubrication, cooling, process speed, etc. Whilemore » thermal management is a key to addressing tooling failures, it was clear that new tooling materials with superior high temperature strength could provide improved manufacturing efficiencies. These efficiencies are based on the use of functionally graded materials (FGM), a new subset of hybrid tools with customizable properties that can be fabricated using advanced powder metallurgy manufacturing technologies. Modeling studies of the various hot forming processes helped identify the effect of key variables such as stress, temperature and cooling rate and aid in the selection of tooling materials for specific applications. To address the problem of high temperature strength, several advanced powder metallurgy nickel and cobalt based alloys were selected for evaluation. These materials were manufactured into tooling using two relatively new consolidation processes. One process involved laser powder deposition (LPD) and the second involved a solid state dynamic powder consolidation (SSDPC) process. These processes made possible functionally graded materials (FGM) that resulted in shaped tooling that was monolithic, bi-metallic or substrate coated. Manufacturing of tooling with these processes was determined to be robust and consistent for a variety of materials. Prototype and production testing of FGM tooling showed the benefits of the nickel and cobalt based powder metallurgy alloys in a number of applications evaluated. Improvements in tool life ranged from three (3) to twenty (20) or more times than currently used tooling. Improvements were most dramatic where tool softening and deformation were the major cause of tool failures in hot/warm forging applications. Significant improvement was also noted in erosion of aluminum die casting tooling. Cost and energy savings can be realized as a result of increased tooling life, increased productivity and a reduction in scrap because of improved dimensional controls. Although LPD and SSDPC tooling usually have higher acquisition costs, net tooling costs per component produced drops dramatically with superior tool performance. Less energy is used to manufacture the tooling because fewer tools are required and less recycling of used tools are needed for the hot forming process. Energy is saved during the component manufacturing cycle because more parts can be produced in shorter periods of time. Energy is also saved by minimizing heating furnace idling time because of less downtime for tooling changes.« less

Advanced Material Strategies for Next-Generation Additive Manufacturing

PubMed Central

Chang, Jinke; He, Jiankang; Zhou, Wenxing; Lei, Qi; Li, Xiao; Li, Dichen

2018-01-01

Additive manufacturing (AM) has drawn tremendous attention in various fields. In recent years, great efforts have been made to develop novel additive manufacturing processes such as micro-/nano-scale 3D printing, bioprinting, and 4D printing for the fabrication of complex 3D structures with high resolution, living components, and multimaterials. The development of advanced functional materials is important for the implementation of these novel additive manufacturing processes. Here, a state-of-the-art review on advanced material strategies for novel additive manufacturing processes is provided, mainly including conductive materials, biomaterials, and smart materials. The advantages, limitations, and future perspectives of these materials for additive manufacturing are discussed. It is believed that the innovations of material strategies in parallel with the evolution of additive manufacturing processes will provide numerous possibilities for the fabrication of complex smart constructs with multiple functions, which will significantly widen the application fields of next-generation additive manufacturing. PMID:29361754

Advanced Material Strategies for Next-Generation Additive Manufacturing.

PubMed

Chang, Jinke; He, Jiankang; Mao, Mao; Zhou, Wenxing; Lei, Qi; Li, Xiao; Li, Dichen; Chua, Chee-Kai; Zhao, Xin

2018-01-22

Additive manufacturing (AM) has drawn tremendous attention in various fields. In recent years, great efforts have been made to develop novel additive manufacturing processes such as micro-/nano-scale 3D printing, bioprinting, and 4D printing for the fabrication of complex 3D structures with high resolution, living components, and multimaterials. The development of advanced functional materials is important for the implementation of these novel additive manufacturing processes. Here, a state-of-the-art review on advanced material strategies for novel additive manufacturing processes is provided, mainly including conductive materials, biomaterials, and smart materials. The advantages, limitations, and future perspectives of these materials for additive manufacturing are discussed. It is believed that the innovations of material strategies in parallel with the evolution of additive manufacturing processes will provide numerous possibilities for the fabrication of complex smart constructs with multiple functions, which will significantly widen the application fields of next-generation additive manufacturing.

Optimisation of the manufacturing process of tritide and deuteride targets used for neutron production

NASA Astrophysics Data System (ADS)

Monnin, Carole; Bach, Pierre; Tulle, Pierre Alain; van Rompay, Marc; Ballanger, Anne

2002-03-01

As a neutron tube manufacturer, SODERN is now in charge of manufacturing tritium targets for accelerators, in cooperation with CEA/DAM/DTMN in Valduc. Specific deuterium and tritium targets are manufactured on request, according to the requirements of the users, starting from titanium targets on copper substrates, and going to more sophisticated devices. The range of possible uses is wide, including thin targets for neutron calibration, thick targets with controlled loading of deuterium and tritium, rotating targets or large size rotating targets for higher lifetimes. The activity of the targets ranges from 3.7×10 10 to 3.7×10 13 Bq (1-1000 Ci), the diameter being up to 30 cm. Sodern and the CEA/Valduc centre have developed different technologies for tritium target manufacture, allowing the selection of the best configuration for each kind of use. In order to optimize the production of high energy neutrons, the performance of tritide and deuteride titanium targets made by different processes has been studied experimentally by bombardment with 120 and 350 kV deuterons provided by electrostatic accelerators. It is then possible to optimize either neutron output or lifetime and stability or thermal behaviour. The importance of the deposit evaporation conditions on the efficiency of neutron emission is clearly demonstrated, as well as the thermomechanical stability of the Ti thin film under deuteron bombardment. The main parameters involved in the target performance are discussed from a thermodynamical approach.

The use of Tecnomatix software to simulate the manufacturing flows in an industrial enterprise producing hydrostatic components

NASA Astrophysics Data System (ADS)

Petrila, S.; Brabie, G.; Chirita, B.

2016-08-01

The analysis performed on manufacturing flows within industrial enterprises producing hydrostatic components twos made on a number of factors that influence smooth running of production such: distance between pieces, waiting time from one surgery to another; time achievement of setups on CNC machines; tool changing in case of a large number of operators and manufacturing complexity of large files [2]. To optimize the manufacturing flow it was used the software Tecnomatix. This software represents a complete portfolio of manufacturing solutions digital manufactured by Siemens. It provides innovation by linking all production methods of a product from process design, process simulation, validation and ending the manufacturing process. Among its many capabilities to create a wide range of simulations, the program offers various demonstrations regarding the behavior manufacturing cycles. This program allows the simulation and optimization of production systems and processes in several areas such as: car suppliers, production of industrial equipment; electronics manufacturing, design and production of aerospace and defense parts.

Research on manufacturing service behavior modeling based on block chain theory

NASA Astrophysics Data System (ADS)

Zhao, Gang; Zhang, Guangli; Liu, Ming; Yu, Shuqin; Liu, Yali; Zhang, Xu

2018-04-01

According to the attribute characteristics of processing craft, the manufacturing service behavior is divided into service attribute, basic attribute, process attribute, resource attribute. The attribute information model of manufacturing service is established. The manufacturing service behavior information is successfully divided into public and private domain. Additionally, the block chain technology is introduced, and the information model of manufacturing service based on block chain principle is established, which solves the problem of sharing and secreting information of processing behavior, and ensures that data is not tampered with. Based on the key pairing verification relationship, the selective publishing mechanism for manufacturing information is established, achieving the traceability of product data, guarantying the quality of processing quality.

Software for integrated manufacturing systems, part 2

NASA Technical Reports Server (NTRS)

Volz, R. A.; Naylor, A. W.

1987-01-01

Part 1 presented an overview of the unified approach to manufacturing software. The specific characteristics of the approach that allow it to realize the goals of reduced cost, increased reliability and increased flexibility are considered. Why the blending of a components view, distributed languages, generics and formal models is important, why each individual part of this approach is essential, and why each component will typically have each of these parts are examined. An example of a specification for a real material handling system is presented using the approach and compared with the standard interface specification given by the manufacturer. Use of the component in a distributed manufacturing system is then compared with use of the traditional specification with a more traditional approach to designing the system. An overview is also provided of the underlying mechanisms used for implementing distributed manufacturing systems using the unified software/hardware component approach.

Role of Process Control in Improving Space Vehicle Safety A Space Shuttle External Tank Example

NASA Technical Reports Server (NTRS)

Safie, Fayssal M.; Nguyen, Son C.; Burleson, Keith W.

2006-01-01

Developing a safe and reliable space vehicle requires good design and good manufacturing, or in other words "design it right and build it right". A great design can be hard to build or manufacture mainly due to difficulties related to quality. Specifically, process control can be a challenge. As a result, the system suffers from low quality which leads to low reliability and high system risk. The Space Shuttle has experienced some of those cases, but has overcome these difficulties through extensive redesign efforts and process enhancements. One example is the design of the hot gas temperature sensor on the Space Shuttle Main Engine (SSME), which resulted in failure of the sensor in flight and led to a redesign of the sensor. The most recent example is the Space Shuttle External Tank (ET) Thermal Protection System (TPS) reliability issues that contributed to the Columbia accident. As a result, extensive redesign and process enhancement activities have been performed over the last two years to minimize the sensitivities and difficulties of the manual TPS application process.

27 CFR 40.525 - Discontinuance of operations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... operations. 40.525 Section 40.525 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE... AND TUBES, AND PROCESSED TOBACCO Manufacture of Processed Tobacco Operations by Manufacturers of Processed Tobacco § 40.525 Discontinuance of operations. Every manufacturer of processed tobacco who desires...

Key technologies for manufacturing and processing sheet materials: A global perspective

NASA Astrophysics Data System (ADS)

Demeri, Mahmoud Y.

2001-02-01

Modern industrial technologies continue to seek new materials and processes to produce products that meet design and functional requirements. Sheet materials made from ferrous and non-ferrous metals, laminates, composites, and reinforced plastics constitute a large percentage of today’s products, components, and systems. Major manufacturers of sheet products include automotive, aerospace, appliance, and food-packaging industries. The Second Global Symposium on Innovations in Materials Processing & Manufacturing: Sheet Materials is organized to provide a forum for presenting advances in sheet processing and manufacturing by worldwide researchers and engineers from industrial, research, and academic centers. The symposium, sponsored by the TMS Materials Processing & Manufacturing Division (MPMD), was planned for the 2001 TMS Annual Meeting, New Orleans, Louisiana, February 11 15, 2001. This article is a review of key papers submitted for publication in the concurrent volume. The selected papers present significant developments in the rapidly expanding areas of advanced sheet materials, innovative forming methods, industrial applications, primary and secondary processing, composite processing, and numerical modeling of manufacturing processes.