Good manufacturing practice-compliant validation and preparation of BM cells for the therapy of acute myocardial infarction

BACKGROUND: Intracoronary application of BM-derived cells for the treatment of acute myocardial infarction (AMI) is currently being studied intensively. Simultaneously, strict legal requirements surround the production of cells for clinical studies. Thus good manufacturing practice (GMP)-compliant collection and preparation of BM for patients with AMI was established by the Cytonet group. METHODS: As well as fulfillment of standard GMP requirements, including a manufacturing license, validation of the preparation process and the final product was performed. Whole blood (n=6) and BM (n=3) validation samples were processed under GMP conditions by gelafundin or hydroxyethylstarch sedimentation in order to reduce erythrocytes/platelets and volume and to achieve specifications defined in advance. Special attention was paid to the free potassium (<6 mmol/L), some rheologically relevant cellular characteristics (hematocrit <0.45, platelets <450 x 10(6)/mL) and the sterility of the final product. RESULTS: The data were reviewed and GMP compliance was confirmed by the German authorities (Paul-Ehrlich Institute). Forty-five BM cell preparations for clinical use were carried out following the validated methodology and standards. Additionally three selections of CD34+ BM cells for infusion were performed. All specification limits were met. Discussion In conclusion, preparation of BM cells for intracoronary application is feasible under GMP conditions. As the results of sterility testing may not be available at the time of intracoronary application, the highest possible standards to avoid bacterial and other contaminations have to be applied. The increased expense of the GMP-compliant process can be justified by higher safety for patients and better control of the final product.

Analysis of a Non-Traditional Micro Tube Hydroforming Process

As the demand for miniature products and components continues to increase, the need for manufacturing processes to provide these products and components has also increased. To meet this need, successful macroscale processes are being scaled down and applied at the microscale. Unfortunately, many challenges have been experienced when directly scaling down macro processes. Initially, frictional effects were believed to be the largest challenge encountered. However, in recent studies it has been found that the greatest challenge encountered has been with size effects. Size effect is a broad term that largely refers to the thickness of the material being formed and how this thickness directly affects the product dimensions and manufacturability. At the microscale, the thickness becomes critical due to the reduced number of grains. When surface contact between the forming tools and the material blanks occur at the macroscale, there is enough material (hundreds of layers of material grains) across the blank thickness to compensate for material flow and the effect of grain orientation. At the microscale, there may be under 10 grains across the blank thickness. With a decreased amount of grains across the thickness, the influence of the grain size, shape and orientation is significant. Any material defects (either natural occurring or ones that occur as a result of the material preparation) have a significant role in altering the forming potential. To date, various micro metal forming and micro materials testing equipment setups have been constructed at the Michigan Tech lab. Initially, the research focus was to create a micro deep drawing setup to potentially build micro sensor encapsulation housings. The research focus shifted to micro metal materials testing equipment setups. These include the construction and testing of the following setups: a micro mechanical bulge test, a micro sheet tension test (testing micro tensile bars), a micro strain analysis (with the use of optical lithography and chemical etching) and a micro sheet hydroforming bulge test. Recently, the focus has shifted to study a micro tube hydroforming process. The intent is to target fuel cells, medical, and sensor encapsulation applications. While the tube hydroforming process is widely understood at the macroscale, the microscale process also offers some significant challenges in terms of size effects. Current work is being conducted in applying direct current to enhance micro tube hydroforming formability. Initially, adding direct current to various metal forming operations has shown some phenomenal results. The focus of current research is to determine the validity of this process.

THE USE OF LIFE-CYCLE ANALYSIS TO REDUCE THE ENVIRONMENTAL IMPACT OF MATERIALS IN MANUFACTURING

This thesis is composed of three life-cycle analysis (LCA) studies of manufacturing to determine cumulative energy demand (CED) and greenhouse gas emissions (GHG). The methods proposed could reduce the environmental impact by reducing the CED in three manufacturing processes. First, industrial symbiosis is proposed and a LCA is performed on both conventional 1 GW-scaled hydrogenated amorphous silicon (a-Si:H)-based single junction and a-Si:H/microcrystalline-Si:H tandem cell solar PV manufacturing plants and such plants coupled to silane recycling plants. Using a recycling process that results in a silane loss of only 17 versus 85 percent, this results in a CED savings of 81,700 GJ and 290,000 GJ per year for single and tandem junction plants, respectively. This recycling process reduces the cost of raw silane by 68 percent, or approximately $22.6 and $79 million per year for a single and tandem 1 GW PV production facility, respectively. The results show environmental benefits of silane recycling centered around a-Si:H-based PV manufacturing plants. Second, an open-source self-replicating rapid prototype or 3-D printer, the RepRap, has the potential to reduce the environmental impact of manufacturing of polymer-based products, using distributed manufacturing paradigm, which is further minimized by the use of PV and improvements in PV manufacturing. Using 3-D printers for manufacturing provides the ability to ultra-customize products and to change fill composition, which increases material efficiency. An LCA was performed on three polymer-based products to determine the CED and GHG from conventional large-scale production and are compared to experimental measurements on a RepRap producing identical products with ABS and PLA. The results of this LCA study indicate that the CED of manufacturing polymer products can possibly be reduced using distributed manufacturing with existing 3-D printers under 89% fill and reduced even further with a solar photovoltaic system. The results indicate that the ability of RepRaps to vary fill has the potential to diminish environmental impact on many products. Third, one additional way to improve the environmental performance of this distributed manufacturing system is to create the polymer filament feedstock for 3-D printers using post-consumer plastic bottles. An LCA was performed on the recycling of high density polyethylene (HDPE) using the RecycleBot. The results of the LCA showed that distributed recycling has a lower CED than the best-case scenario used for centralized recycling. If this process is applied to the HDPE currently recycled in the U.S., more than 100 million MJ of energy could be conserved per annum along with significant reductions in GHG. This presents a novel path to a future of distributed manufacturing suited for both the developed and developing world with reduced environmental impact. From improving manufacturing in the photovoltaic industry with the use of recycling to recycling and manufacturing plastic products within our own homes, each step reduces the impact on the environment. The three coupled projects presented here show a clear potential to reduce the environmental impact of manufacturing and other processes by implementing complimenting systems, which have environmental benefits of their own in order to achieve a compounding effect of reduced CED and GHG.

Rapid Manufacturing - auch mit SLM

Rapid Manufacturing (RM) wurde als Schlagwort in der letzten Zeit insbesondere aus dem Bereich des Selective Laser Sintering (SLS) bekannt. In dieser inzwischen über 15-jährigen Technologieentwicklung wurden in den vergangenen Jahren bedeutende Fortschritte erzielt, die die Bauteileigenschaften nahe an die Anforderungen für End-Teile heran brachten. So ist das RM denn auch weniger aus der Sicht grösserer Losgrösse zu verstehen. Viel mehr bedeutet Rapid Manufacturing, dass die Bauteile nach einer generativen Fertigung direkt im Endprodukt resp. der Endanwendung zum Einsatz kommt. Das Selective Laser Melting, mit welchem aus metallischen Pulvermaterialien direkt Metallteile in Standardmaterialien hergestellt werden können, ist aufgrund der guten Materialeigenschaften für RM prädestiniert. In den ersten Anwendungsfeldern des SLM–Verfahrens standen die Herstellung von Werkzeugeinsätzen mit konturnaher Kühlung (Conformal Cooling) im Vordergrund, wobei diese Werkzeuge unter dem Begriff RM verstanden werden müssen, da die Werkzeuge direkt für die Endanwendung - den Spritzgussprozess - verwendet werden. Aktuelle Trends gehen jedoch in Richtung der Fertigung von Funktionsteilen z.B. für den Maschinenbau. Obwohl sich in der Fertigung komplexer Funktionsteile noch Probleme, z.B. mit in Bezug auf die generative Baurichtung überhängender Bauteilstrukturen ergeben, zeigen sich trotzdem erhebliche Vorteile eines RM mittels SLM. Neben klaren Vorteilen durch das mögliche Customizing von Bauteilen können bei kleineren Bauteilgrössen auch erhebliche Kostenvorteile erzielt werden. Allerdings zeigen die Grenzen der aktuellen Möglichkeiten, in welchen Bereichen das SLM-Verfahren weiterer Entwicklung bedarf. Themen wie Produktivität, die Problematik der nach wie vor notwendigen Supportstrukturen wie auch Qualitätssicherung müssen in den nächsten Jahren angegangen werden, wenn dieses Verfahren den Schritt hin zu einem etablierten Produktionsverfahren und damit zu breiterer Akzeptanz und Anwendung finden soll

Auslegung, Konstruktion und Fertigung von strömungsmechanischen Funktionsprototypen mittels Rapid Manufacturing

Bei der Fertigung von Funktionsbauteilen für Strömungsversuche spielt das Design und die Komplexität der Bauteilgeometrie eine wesentliche Rolle. Ziel der interdisziplinären Zusammenarbeit der Lehrstühle Strömungsmaschinen, Rechnereinsatz in der Konstruktion und Fertigungstechnik mit dem Rapid Technology Center (RTC) an der Universität Duisburg-Essen ist es, das Potenzial der additiven Fertigungsverfahren bei der Herstellung von Funktionsprototypen für strömungsmechanische Anwendungen effektiv zu nutzen. An verschiedenen, auf dieser Kooperation beruhenden, Best Practise Beispielen wird gezeigt wie das Laser-Sintern in die Prozesskette zur Herstellung von Laufrädern u. Ä. in unterschiedlichen Größenordnungen integriert werden kann. In diesem Zusammenhang werden auch die Vorüberlegungen (z. B. durch Simulation), Wechselwirkungen und Folgeprozesse, die mit dieser Fertigungstechnologie verbunden sind, aufgezeigt.

Auslegung, Konstruktion und Fertigung von strömungsmechanischen Funktionsprototypen mittels Rapid Manufacturing

Bei der Fertigung von Funktionsbauteilen für Strömungsversuche spielt das Design und die Komplexität der Bauteilgeometrie eine wesentliche Rolle. Ziel der interdisziplinären Zusammenarbeit der Lehrstühle Strömungsmaschinen, Rechnereinsatz in der Konstruktion und Fertigungstechnik mit dem Rapid Technology Center (RTC) an der Universität Duisburg-Essen ist es, das Potenzial der additiven Fertigungsverfahren bei der Herstellung von Funktionsprototypen für strömungsmechanische Anwendungen effektiv zu nutzen. An verschiedenen, auf dieser Kooperation beruhenden, Best Practise Beispielen wird gezeigt wie das Laser-Sintern in die Prozesskette zur Herstellung von Laufrädern u. Ä. in unterschiedlichen Größenordnungen integriert werden kann. In diesem Zusammenhang werden auch die Vorüberlegungen (z. B. durch Simulation), Wechselwirkungen und Folgeprozesse, die mit dieser Fertigungstechnologie verbunden sind, aufgezeigt.

Planning of a make-to-order production process in the printing industry

Offset printing is a common method to produce large amounts of printed matter. We consider a real-world offset printing process that is used to imprint customer-specific designs on napkin pouches. The production equipment used gives rise to various technological constraints. The planning problem consists of allocating designs to printing-plate slots such that the given customer demand for each design is fulfilled, all technological and organizational constraints are met and the total overproduction and setup costs are minimized. We formulate this planning problem as a mixed-binary linear program, and we develop a multi-pass matching-based savings heuristic. We report computational results for a set of problem instances devised from real-world data.

Production Streamlining through Design, Implementation, and Analysis of Lean Manufacturing Methods

Through the correct implementation of lean manufacturing methods, a company can greatly improve their business. Over a period of three months at TTM Technologies, I utilized my knowledge to fix existing problems ans streamline production. In addition, other trouble areas in their production process were discovered and proper lean methods were used to address them. TTM Technologies saw many changed in the right direction over this time period.

A descriptive and exploratory analysis of occupational injuries at a chemical manufacturing facility

A retrospective study of 1353 occupational injuries occurring at a chemical manufacturing facility in Houston, Texas from January, 1982 through May, 1988 was performed to investigate the etiology of the occupational injury process. Injury incidence rates were calculated for various sub-populations of workers to determine differences in the risk of injury for various groups. Linear modeling techniques were used to determine the association between certain collected independent variables and severity of an injury event. Finally, two sub-groups of the worker population, shiftworkers and injury recidivists, were examined. An injury recidivist as defined is any worker experiencing one or more injury per year. Overall, female shiftworkers evidenced the highest average injury incidence rate compared to all other worker groups analyzed. Although the female shiftworkers were younger and less experienced, the etiology of their increased risk of injury remains unclear, although the rigors of performing shiftwork itself or ergonomic factors are suspect. In general, females were injured more frequently than males, but they did not incur more severe injuries. For all workers, many injuries were caused by erroneous or foregone training, and risk taking behaviors. Injuries of these types are avoidable. The distribution of injuries by severity level was bimodal; either injuries were of minor or major severity with only a small number of cases falling in between. Of the variables collected, only the type of injury incurred and the worker's titlecode were statistically significantly associated with injury severity. Shiftworkers did not sustain more severe injuries than other worker groups. Injury to shiftworkers varied as a 24-hour pattern; the greatest number occurred between 1200-1230 hours, (p = 0.002) by Cosinor analysis. Recidivists made up 3.3% of the population (23 males and 10 females), yet suffered 17.8% of the injuries. Although past research suggests that injury recidivism is a random statistical event, analysis of the data by logistic regression implicates gender, area worked, age and job titlecode as being statistically significantly related to injury recidivism at this facility. ^

International Competitiveness of Manufacturing Firms in sub-Saharan Africa

As the success of East Asian countries has shown, labor-intensive industry is recognized to lead economic growth in the early stages of development, utilizing relatively low labor costs. This same growth process has already started in South and South East Asian LDCs since the mid-1990s. However, the manufacturing sector in sub-Saharan Africa has been underdeveloped and manufacturing exports, in particular labour-intensive goods, have stagnated. This paper investigates the international competitiveness of the African manufacturing sector and its determinants through an analytical survey of empirical studies and a comparison with Asian low income countries. Empirical evidences indicate that primary factors of competitiveness, namely productivity, labour cost and exchange rate are unfavorable in sub-Saharan Africa. Representative arguments attribute the weak competitiveness to problems in the business environment, factor endowment, and the exchange rate. However, careful review shows that labour cost is beyond the range explained by endowment and misalignment of exchange rates have been reduced in Africa. Moreover, comparison with Asian low income countries which have competitiveness in labour-intensive goods shows no difference in the quality of business environment, while the labour cost is significantly lower than sub-Saharan African countries. Although results should be considered tentative, high labour cost beyond endowment and conservative investment behavior emerge as important factors for the weak competitiveness in sub-Saharan Africa when controlling income level.

Knowledge spillover in Indian automobile industry : the process and the coverage

In India, as the production of passenger cars increased, many local small and medium enterprises (SMEs) entered the parts and components manufacturing sector. The sources of knowledge for large enterprises and SMEs are different. Naturally, spillover effects among large enterprises and between large enterprises and SMEs are different. This paper focuses on knowledge spillover among large enterprises and from large enterprises to SMEs. Subcontractor can absorb relation-specific skills through repeated interaction with parent company. The results of field survey emphasizes that relation-specific skills are a determinant factor of spillover effects from assemblers and large auto component manufacturers to SMEs. Econometric analysis shows that spillover effects among medium and large automobile units and from medium and large automobile units to small units went beyond boundary of cluster.

The location of manufacturing firms and imperfect information in transport market

It is well know that transport charges are not symmetric: fronthaul and backhaul costs on a route may differ, because they are affected by the distribution of economic acitivities. This paper develops a two-regional general equilibrium model in which transport costs are determined endogenously as a result of a search and matching process. It is shown that economies or diseconomies of transport density emerge, depending on the search costs of transport firms and the relative importance of the possibility of backhaul transportation. It is found that the symmetry of the distribution of economic activity may break owing to economies of transport density when the additional search costs are small enough.

Design, manufacturing and measurements of a metal-less V-groove RXI collimator

A metal-less RXI collimator has been designed. Unlike to the conventional RXI collimators, whose back surface and central part of the front surface have to be metalized, this collimator does not include any mirrored surface. The back surface is designed as a grooved surface providing two TIR reflections for all rays impinging on it. The main advantage of the presented design is lower manufacturing cost since there is no need for the expensive process of metalization. Also, unlike to the conventional RXI collimators this design performs good colour mixing. The first prototype of V-groove RXI collimator has been made of PMMA by direct cutting using a five axis diamond turning machine. The experimental measurements of the first prototype are presented.

The role of a firm's absorptive capacity and the technology transfer process in clusters: How effective are technology centres in low-tech clusters?

This paper analyses how the internal resources of small- and medium-sized enterprises determine access (learning processes) to technology centres (TCs) or industrial research institutes (innovation infrastructure) in traditional low-tech clusters. These interactions basically represent traded (market-based) transactions, which constitute important sources of knowledge in clusters. The paper addresses the role of TCs in low-tech clusters, and uses semi-structured interviews with 80 firms in a manufacturing cluster. The results point out that producer–user interactions are the most frequent; thus, the higher the sector knowledge-intensive base, the more likely the utilization of the available research infrastructure becomes. Conversely, the sectors with less knowledge-intensive structures, i.e. less absorptive capacity (AC), present weak linkages to TCs, as they frequently prefer to interact with suppliers, who act as transceivers of knowledge. Therefore, not all the firms in a cluster can fully exploit the available research infrastructure, and their AC moderates this engagement. In addition, the existence of TCs is not sufficient since the active role of a firm's search strategies to undertake interactions and conduct openness to available sources of knowledge is also needed. The study has implications for policymakers and academia.

Activity based costing, time-driven activity based costing and lean accounting: differences among three accounting systems' approach to manufacturing

Choosing an appropriate accounting system for manufacturing has always been a challenge for managers. In this article we try to compare three accounting systems designed since 1980 to address problems of traditional accounting system. In the first place we are going to present a short overview on background and definition of three accounting systems: Activity Based costing, Time-Driven Activity Based Costing and Lean Accounting. Comparisons are made based on the three basic roles of information generated by accounting systems: financial reporting, decision making, and operational control and improvement. The analysis in this paper reveals how decisions are made over the value stream in the companies using Lean Accounting while decisions under the ABC Accounting system are taken at individual product level, and finally we will show how TD-ABC covers both product and process levels for decision making. In addition, this paper shows the importance of nonfinancial measures for operational control and improvement under the Lean Accounting and TD-ABC methods whereas ABC relies mostly on financial measures in this context.