To Stretch the Boundary of Secondary Metabolite Production in Plant Cell-Based Bioprocessing: Anthocyanin as a Case Study

Directory of Open Access Journals (Sweden)

Wei Zhang

2004-01-01

Full Text Available Plant cells and tissue cultures hold great promise for controlled production of a myriad of useful secondary metabolites on demand. The current yield and productivity cannot fulfill the commercial goal of a plant cell-based bioprocess for the production of most secondary metabolites. In order to stretch the boundary, recent advances, new directions and opportunities in plant cell-based bioprocessing, have been critically examined for the 10 years from 1992 to 2002. A review of the literature indicated that most of the R&D work was devoted predominantly to studies at an empirical level. A rational approach to molecular plant cell bioprocessing based on the fundamental understanding of metabolic pathways and their regulations is urgently required to stimulate further advances; however, the strategies and technical framework are still being developed. It is the aim of this review to take a step forward in framing workable strategies and technologies for molecular plant cell-based bioprocessing. Using anthocyanin biosynthesis as a case study, an integrated postgenomic approach has been proposed. This combines the functional analysis of metabolic pathways for biosynthesis of a particular metabolite from profiling of gene expression and protein expression to metabolic profiling. A global correlation not only can thus be established at the three molecular levels, but also places emphasis on the interactions between primary metabolism and secondary metabolism; between competing and/or complimentary pathways; and between biosynthetic and post-biosynthetic events.

Establishing new microbial cell factories for sustainable bioprocesses

DEFF Research Database (Denmark)

Workman, Mhairi; Holt, Philippe; Liu, Xiaoying

2012-01-01

. The application of biological catalysts which can convert a variety of substrates to an array of desirable products has been demonstrated in both ancient bioprocesses and modern industrial biotechnology. In recent times, focus has been on a limited number of “model” organisms which have been extensively exploited...... of products, it may be interesting to look to less domesticated strains and towards more non-conventional hosts in the development of new bioprocesses. This approach demands thorough physiological characterization as well as establishment of tools for genetic engineering if new cell factories......The demands of modern society are increasing pressure on natural resources while creating the need for a wider range of products. There is an interest in developing bioprocesses to meet these demands, with conversion of a variety of waste materials providing the basis for a sustainable society...

Disposable bioprocessing: the future has arrived.

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Rao, Govind; Moreira, Antonio; Brorson, Kurt

2009-02-01

Increasing cost pressures are driving the rapid adoption of disposables in bioprocessing. While well ensconced in lab-scale operations, the lower operating/ validation costs at larger scale and relative ease of use are leading to these systems entering all stages and operations of a typical biopharmaceutical manufacturing process. Here, we focus on progress made in the incorporation of disposable equipment with sensor technology in bioprocessing throughout the development cycle. We note that sensor patch technology is mostly being adapted to disposable cell culture devices, but future adaptation to downstream steps is conceivable. Lastly, regulatory requirements are also briefly assessed in the context of disposables and the Process Analytical Technologies (PAT) and Quality by Design (QbD) initiatives.

Incorporating unnatural amino acids to engineer biocatalysts for industrial bioprocess applications.

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Ravikumar, Yuvaraj; Nadarajan, Saravanan Prabhu; Hyeon Yoo, Tae; Lee, Chong-Soon; Yun, Hyungdon

2015-12-01

The bioprocess engineering with biocatalysts broadly spans its development and actual application of enzymes in an industrial context. Recently, both the use of bioprocess engineering and the development and employment of enzyme engineering techniques have been increasing rapidly. Importantly, engineering techniques that incorporate unnatural amino acids (UAAs) in vivo has begun to produce enzymes with greater stability and altered catalytic properties. Despite the growth of this technique, its potential value in bioprocess applications remains to be fully exploited. In this review, we explore the methodologies involved in UAA incorporation as well as ways to synthesize these UAAs. In addition, we summarize recent efforts to increase the yield of UAA engineered proteins in Escherichia coli and also the application of this tool in enzyme engineering. Furthermore, this protein engineering tool based on the incorporation of UAA can be used to develop immobilized enzymes that are ideal for bioprocess applications. Considering the potential of this tool and by exploiting these engineered enzymes, we expect the field of bioprocess engineering to open up new opportunities for biocatalysis in the near future. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A comparative neutron activation analysis study of common generic manipulated and reference medicines commercialized in Brazil

International Nuclear Information System (INIS)

Leal, A.S.; Menezes, M.A.B.C.; Rodrigues, R.R.; Andonie, O.; Vermaercke, P.; Sneyers, L.

2008-01-01

In this work, a comparative study of neutron activation analysis (NAA) was performed by the nuclear institutes: CDTN/CNEN-Brazil, CCHEN-Chile and the SCK.CEN-Belgium aiming to investigate some generic, manipulated and reference medicines largely commercialized in Brazil. Some impurities such as: As, Ba, Br, Ce, Co, Cr, Eu, Fe, Hf, Sb, Sc, Sm, Ti and Zn were found, and the heterogeneity of the samples pointed out the lack of an efficient public system of quality control

Benefits of Digital Equipment Generic Qualification Activities

International Nuclear Information System (INIS)

Thomas, James E.; Steiman, Samuel C.

2002-01-01

As a result of nuclear power plant instrumentation and control obsolescence issues, there have been numerous activities during recent years relating to the qualification of digital equipment. Some of these activities have been 'generic' in nature in that the qualification was not limited to plant specific applications, but was intended to cover a broad base of potential applications of the digital equipment. These generic qualifications have been funded by equipment manufacturers and by utility groups and organizations. The generic activities sponsored by the Electric Power Research Institute (EPRI) have been pilot projects for an overall generic qualification approach. The primary benefit resulting from the generic qualification work to date is that a number of digital platforms and digital devices are now available for use in various nuclear safety-related applications. Many of the tests and evaluations necessary to support plant specific applications have been completed. The amount of data and documentation that each utility must develop on a case by case basis has been significantly reduced. There are also a number of additional benefits resulting from these industry efforts. The challenges and difficulties in qualifying digital equipment for safety-related applications are now more clearly understood. EPRI has published a lessons learned document (EPRI Report 1001452, Generic Qualification of Commercial Grade Digital Devices: Lessons Learned from Initial Pilots, which covers several different qualification areas, including device selection, project planning, vendor surveys and design reviews, and electromagnetic compatibility (EMC) qualification. Application of the experience and lessons learned from the EPRI pilot activities should help reduce the effort and cost required for future qualification work. Most generic qualification activities for commercial equipment have been conducted using the approach of EPRI TR-106439, Guideline on Evaluation and Acceptance

Bioprocessing automation in cell therapy manufacturing: Outcomes of special interest group automation workshop.

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Ball, Oliver; Robinson, Sarah; Bure, Kim; Brindley, David A; Mccall, David

2018-04-01

Phacilitate held a Special Interest Group workshop event in Edinburgh, UK, in May 2017. The event brought together leading stakeholders in the cell therapy bioprocessing field to identify present and future challenges and propose potential solutions to automation in cell therapy bioprocessing. Here, we review and summarize discussions from the event. Deep biological understanding of a product, its mechanism of action and indication pathogenesis underpin many factors relating to bioprocessing and automation. To fully exploit the opportunities of bioprocess automation, therapeutics developers must closely consider whether an automation strategy is applicable, how to design an 'automatable' bioprocess and how to implement process modifications with minimal disruption. Major decisions around bioprocess automation strategy should involve all relevant stakeholders; communication between technical and business strategy decision-makers is of particular importance. Developers should leverage automation to implement in-process testing, in turn applicable to process optimization, quality assurance (QA)/ quality control (QC), batch failure control, adaptive manufacturing and regulatory demands, but a lack of precedent and technical opportunities can complicate such efforts. Sparse standardization across product characterization, hardware components and software platforms is perceived to complicate efforts to implement automation. The use of advanced algorithmic approaches such as machine learning may have application to bioprocess and supply chain optimization. Automation can substantially de-risk the wider supply chain, including tracking and traceability, cryopreservation and thawing and logistics. The regulatory implications of automation are currently unclear because few hardware options exist and novel solutions require case-by-case validation, but automation can present attractive regulatory incentives. Copyright © 2018 International Society for Cellular Therapy

Quantitative feature extraction from the Chinese hamster ovary bioprocess bibliome using a novel meta-analysis workflow

DEFF Research Database (Denmark)

Golabgir, Aydin; Gutierrez, Jahir M.; Hefzi, Hooman

2016-01-01

compilation covers all published CHO cell studies from 1995 to 2015, and each study is classified by the types of phenotypic and bioprocess data contained therein. Using data from selected studies, we also present a quantitative meta-analysis of bioprocess characteristics across diverse culture conditions...... practices can limit research re-use in this field, we show that the statistical analysis of diverse legacy bioprocess data can provide insight into bioprocessing capabilities of CHO cell lines used in industry. The CHO bibliome can be accessed at http://lewislab.ucsd.edu/cho-bibliome/....

Developing a Continuous Bioprocessing Approach to Stromal Cell Manufacture.

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Miotto, Martina; Gouveia, Ricardo; Abidin, Fadhilah Zainal; Figueiredo, Francisco; Connon, Che J

2017-11-29

To this day, the concept of continuous bioprocessing has been applied mostly to the manufacture of molecular biologics such as proteins, growth factors, and secondary metabolites with biopharmaceutical uses. The present work now sets to explore the potential application of continuous bioprocess methods to source large numbers of human adherent cells with potential therapeutic value. To this purpose, we developed a smart multifunctional surface coating capable of controlling the attachment, proliferation, and subsequent self-detachment of human corneal stromal cells. This system allowed the maintenance of cell cultures under steady-state growth conditions, where self-detaching cells were continuously replenished by the proliferation of those remaining attached. This facilitated a closed, continuous bioprocessing platform with recovery of approximately 1% of the total adherent cells per hour, a yield rate that was maintained for 1 month. Moreover, both attached and self-detached cells were shown to retain their original phenotype. Together, these results represent the proof-of-concept for a new high-throughput, high-standard, and low-cost biomanufacturing strategy with multiple potentials and important downstream applications.

Potentials and limitations of miniaturized calorimeters for bioprocess monitoring.

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Maskow, Thomas; Schubert, Torsten; Wolf, Antje; Buchholz, Friederike; Regestein, Lars; Buechs, Jochen; Mertens, Florian; Harms, Hauke; Lerchner, Johannes

2011-10-01

In theory, heat production rates are very well suited for analysing and controlling bioprocesses on different scales from a few nanolitres up to many cubic metres. Any bioconversion is accompanied by a production (exothermic) or consumption (endothermic) of heat. The heat is tightly connected with the stoichiometry of the bioprocess via the law of Hess, and its rate is connected to the kinetics of the process. Heat signals provide real-time information of bioprocesses. The combination of heat measurements with respirometry is theoretically suited for the quantification of the coupling between catabolic and anabolic reactions. Heat measurements have also practical advantages. Unlike most other biochemical sensors, thermal transducers can be mounted in a protected way that prevents fouling, thereby minimizing response drifts. Finally, calorimetry works in optically opaque solutions and does not require labelling or reactants. It is surprising to see that despite all these advantages, calorimetry has rarely been applied to monitor and control bioprocesses with intact cells in the laboratory, industrial bioreactors or ecosystems. This review article analyses the reasons for this omission, discusses the additional information calorimetry can provide in comparison with respirometry and presents miniaturization as a potential way to overcome some inherent weaknesses of conventional calorimetry. It will be discussed for which sample types and scientific question miniaturized calorimeter can be advantageously applied. A few examples from different fields of microbiological and biotechnological research will illustrate the potentials and limitations of chip calorimetry. Finally, the future of chip calorimetry is addressed in an outlook.

Raman spectroscopy as a process analytical technology for pharmaceutical manufacturing and bioprocessing.

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Esmonde-White, Karen A; Cuellar, Maryann; Uerpmann, Carsten; Lenain, Bruno; Lewis, Ian R

2017-01-01

Adoption of Quality by Design (QbD) principles, regulatory support of QbD, process analytical technology (PAT), and continuous manufacturing are major factors effecting new approaches to pharmaceutical manufacturing and bioprocessing. In this review, we highlight new technology developments, data analysis models, and applications of Raman spectroscopy, which have expanded the scope of Raman spectroscopy as a process analytical technology. Emerging technologies such as transmission and enhanced reflection Raman, and new approaches to using available technologies, expand the scope of Raman spectroscopy in pharmaceutical manufacturing, and now Raman spectroscopy is successfully integrated into real-time release testing, continuous manufacturing, and statistical process control. Since the last major review of Raman as a pharmaceutical PAT in 2010, many new Raman applications in bioprocessing have emerged. Exciting reports of in situ Raman spectroscopy in bioprocesses complement a growing scientific field of biological and biomedical Raman spectroscopy. Raman spectroscopy has made a positive impact as a process analytical and control tool for pharmaceutical manufacturing and bioprocessing, with demonstrated scientific and financial benefits throughout a product's lifecycle.

Retailing policies for generic medicines.

Science.gov (United States)

Narciso, Susana

2005-06-01

As there is general disagreement about the way generic medicines should be commercialized, two retailing policies are analyzed, taking into account their effects on the welfare of patients, government, pharmacies and physicians. In the first policy scenario, pharmacies are allowed to substitute generic medicines for branded ones, while in the second, substitution is forbidden. In both cases a pharmacies association is allowed to have a share in the production of generic medicines. The model predicts that under some conditions patients may prefer substitution by pharmacies but when doctors' decisions are binding, they are never "excessively bad". However, the policy choice belongs to the government, which prefers to allow for substitution more often than patients would like.

Design and analysis of heat recovery system in bioprocess plant

International Nuclear Information System (INIS)

Anastasovski, Aleksandar; Rašković, Predrag; Guzović, Zvonimir

2015-01-01

Highlights: • Heat integration of a bioprocess plant is studied. • Bioprocess plant produces yeast and ethyl-alcohol. • The design of a heat recovery system is performed by batch pinch analysis. • Direct and indirect heat integration approaches are used in process design. • The heat recovery system without a heat storage opportunity is more profitable. - Abstract: The paper deals with the heat integration of a bioprocess plant which produces yeast and ethyl-alcohol. The referent plant is considered to be a multiproduct batch plant which operates in a semi-continuous mode. The design of a heat recovery system is performed by batch pinch analysis and by the use of the Time slice model. The results obtained by direct and indirect heat integration approaches are presented in the form of cost-optimal heat exchanger networks and evaluated by different thermodynamic and economic indicators. They signify that the heat recovery system without a heat storage opportunity can be considered to be a more profitable solution for the energy efficiency increase in a plant

Some drugs more equal than others: pseudo-generics and commercial practice.

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Probyn, Andrew J

2004-11-08

This article analyses the impact of the Department of Health and Ageing's brand price premium policy for some products listed on the Pharmaceutical Benefits Scheme. The policy, introduced in 1990, allows pharmaceutical companies to charge patients an out-of-pocket expense for post-patent brands of pharmaceuticals. One of the policy's intended goals was to increase consumer awareness of price differentials between competing brands, with a view to encouraging greater use of cheaper generic products. More than fourteen years since its introduction, it is debatable whether the policy has achieved this aim. This article looks at how the brand price premium policy can be exploited by global pharmaceutical giants to entrench big-name brands in the Australian pharmaceutical market and, in some cases, prevent 'true' competition from generic pharmaceuticals. This is being done through the establishment of 'pseudo-generics' that are sourced from the same factory floor as the original product.

Virtual parameter-estimation experiments in Bioprocess-Engineering education

NARCIS (Netherlands)

Sessink, O.D.T.; Beeftink, H.H.; Hartog, R.J.M.; Tramper, J.

2006-01-01

Cell growth kinetics and reactor concepts constitute essential knowledge for Bioprocess-Engineering students. Traditional learning of these concepts is supported by lectures, tutorials, and practicals: ICT offers opportunities for improvement. A virtual-experiment environment was developed that

Generic medicines: solutions for a sustainable drug market?

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Dylst, Pieter; Vulto, Arnold; Godman, Brian; Simoens, Steven

2013-10-01

Generic medicines offer equally high-quality treatment as originator medicines do at much lower prices. As such, they represent a considerable opportunity for authorities to obtain substantial savings. At the moment, the pharmaceutical landscape is changing and many pharmaceutical companies have altered their development and commercial strategies, combining both originator and generic divisions. In spite of this, the generic medicines industry is currently facing a number of challenges: delayed market access; the limited price differential with originator medicines; the continuous downwards pressure on prices; and the negative perception regarding generic medicines held by some key stakeholder groups. This could jeopardize the long-term sustainability of the generic manufacturing industry. Therefore, governments must focus on demand-side policies, alongside policies to accelerate market access, as the generic medicines industry will only be able to deliver competitive and sustainable prices if they are ensured a high volume. In the future, the generic medicines industry will increasingly look to biosimilars and generic versions of orphan drugs to expand their business.

Application of Hydrodynamic Cavitation for Food and Bioprocessing

Science.gov (United States)

Gogate, Parag R.

Hydrodynamic cavitation can be simply generated by the alterations in the flow field in high speed/high pressure devices and also by passage of the liquid through a constriction such as orifice plate, venturi, or throttling valve. Hydrodynamic cavitation results in the formation of local hot spots, release of highly reactive free radicals, and enhanced mass transfer rates due to turbulence generated as a result of liquid circulation currents. These conditions can be suitably applied for intensification of different bioprocessing applications in an energy-efficient manner as compared to conventionally used ultrasound-based reactors. The current chapter aims at highlighting different aspects related to hydrodynamic cavitation, including the theoretical aspects for optimization of operating parameters, reactor designs, and overview of applications relevant to food and bioprocessing. Some case studies highlighting the comparison of hydrodynamic cavitation and acoustic cavitation reactors will also be discussed.

Soft sensors in bioprocessing: A status report and recommendations

DEFF Research Database (Denmark)

Luttmann, Reiner; Bracewell, Daniel G.; Cornelissen, Gesine

2012-01-01

The following report with recommendations is the result of an expert panel meeting on soft sensor applications in bioprocess engineering that was organized by the Measurement, Monitoring, Modelling and Control (M3C) Working Group of the European Federation of Biotechnology - Section of Biochemical...... Engineering Science (ESBES). The aim of the panel was to provide an update on the present status of the subject and to identify critical needs and issues for the furthering of the successful development of soft sensor methods in bioprocess engineering research and for industrial applications, in particular...... with focus on biopharmaceutical applications. It concludes with a set of recommendations, which highlight current prospects for the extended use of soft sensors and those areas requiring development....

Phytosanitary irradiation of fresh tropical commodities in Hawaii: Generic treatments, commercial adoption, and current issues

International Nuclear Information System (INIS)

Follett, Peter A.; Weinert, Eric D.

2012-01-01

Hawaii is a pioneer in the use of phytosanitary irradiation. The commercial X-ray irradiation facility, Hawaii Pride LLC, has been shipping papaya and other tropical fruits and vegetables to the United States mainland using irradiation for 11 years. Irradiation is an approved treatment to control quarantine pests in 17 fruits and 7 vegetables for export from Hawaii to the US mainland. Hawaiian purple sweet potato is the highest volume product with annual exports of more than 12 million lbs (5500 t). The advent of generic radiation treatments for tephritid fruit flies (150 Gy) and other insects (400 Gy) will accelerate commodity export approvals and facilitate worldwide adoption. Lowering doses for specific pests and commodities can lower treatment costs and increase capacity owing to shorter treatment times, and will minimize any quality problems. Current impediments to wider adoption include the 1 kGy limit for fresh horticultural products, the labeling requirement, and non-acceptance of phytosanitary irradiation in Japan, the European Union, and elsewhere. Irradiation has potential as a treatment for unregulated imports to prevent new pest incursions. - Highlights: ► Irradiation is used to control quarantine insects in exported fresh commodities. ► Hawaii exported 5.7 t of tropical produce using irradiation in 2010. ► Generic radiation treatments will accelerate commodity export approvals. ► Lowering the dose for specific commodities will reduce costs/maintain quality. ► Current issues include the 1 kGy dose limit and labeling requirements.

White paper on continuous bioprocessing. May 20-21, 2014 Continuous Manufacturing Symposium.

Science.gov (United States)

Konstantinov, Konstantin B; Cooney, Charles L

2015-03-01

There is a growing interest in realizing the benefits of continuous processing in biologics manufacturing, which is reflected by the significant number of industrial and academic researchers who are actively involved in the development of continuous bioprocessing systems. These efforts are further encouraged by guidance expressed in recent US FDA conference presentations. The advantages of continuous manufacturing include sustained operation with consistent product quality, reduced equipment size, high-volumetric productivity, streamlined process flow, low-process cycle times, and reduced capital and operating cost. This technology, however, poses challenges, which need to be addressed before routine implementation is considered. This paper, which is based on the available literature and input from a large number of reviewers, is intended to provide a consensus of the opportunities, technical needs, and strategic directions for continuous bioprocessing. The discussion is supported by several examples illustrating various architectures of continuous bioprocessing systems. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Selection of bioprocess simulation software for industrial applications.

Science.gov (United States)

Shanklin, T; Roper, K; Yegneswaran, P K; Marten, M R

2001-02-20

Two commercially available, process-simulation software packages (Aspen Batch Plus v1.2, Aspen Technology, Inc., Cambridge, Massachusetts, and Intelligen SuperPro v3.0, INTELLIGEN, INC., Scotch Plains, Ner Jersey) are evaluated for use in modeling industrial, biotechnology processes. Software is quantitatively evaluated by Kepner-Tregoe Decision Analysis (Kepner and Tregoe, 1981). This evaluation shows that Aspen Batch Plus v1.2 (ABP) and Intelligen SuperPro v3.0 (ISP) can successfully perform specific simulation tasks but do not provide a complete model of all phenomena occurring within a biotechnology process. Software is best suited to provide a format for process management, using material and energy balances to answer scheduling questions, explore equipment change-outs, and calculate cost data. The ability of simulation software to accurately predict unit operation scale-up and optimize bioprocesses is limited. To realistically evaluate the software, a vaccine manufacturing process under development at Merck & Company is simulated. Case studies from the vaccine process are presented as examples of how ABP and ISP can be used to shed light on real-world processing issues. Copyright 2001 John Wiley & Sons, Inc.

Efficient and reproducible mammalian cell bioprocesses without probes and controllers?

Science.gov (United States)

Tissot, Stéphanie; Oberbek, Agata; Reclari, Martino; Dreyer, Matthieu; Hacker, David L; Baldi, Lucia; Farhat, Mohamed; Wurm, Florian M

2011-07-01

Bioprocesses for recombinant protein production with mammalian cells are typically controlled for several physicochemical parameters including the pH and dissolved oxygen concentration (DO) of the culture medium. Here we studied whether these controls are necessary for efficient and reproducible bioprocesses in an orbitally shaken bioreactor (OSR). Mixing, gas transfer, and volumetric power consumption (P(V)) were determined in both a 5-L OSR and a 3-L stirred-tank bioreactor (STR). The two cultivation systems had a similar mixing intensity, but the STR had a lower volumetric mass transfer coefficient of oxygen (k(L)a) and a higher P(V) than the OSR. Recombinant CHO cell lines expressing either tumor necrosis factor receptor as an Fc fusion protein (TNFR:Fc) or an anti-RhesusD monoclonal antibody were cultivated in the two systems. The 5-L OSR was operated in an incubator shaker with 5% CO(2) in the gas environment but without pH and DO control whereas the STR was operated with or without pH and DO control. Higher cell densities and recombinant protein titers were obtained in the OSR as compared to both the controlled and the non-controlled STRs. To test the reproducibility of a bioprocess in a non-controlled OSR, the two CHO cell lines were each cultivated in parallel in six 5-L OSRs. Similar cell densities, cell viabilities, and recombinant protein titers along with similar pH and DO profiles were achieved in each group of replicates. Our study demonstrated that bioprocesses can be performed in OSRs without pH or DO control in a highly reproducible manner, at least at the scale of operation studied here. Copyright © 2011 Elsevier B.V. All rights reserved.

Bioprocess intensification for the effective production of chemical products

DEFF Research Database (Denmark)

Woodley, John

2017-01-01

The further implementation of new bioprocesses, using biocatalysts in various formats, for the synthesis of chemicals is highly dependent upon effective process intensification. The need for process intensification reflects the fact that the conditions under which a biocatalyst carries out...... a reaction in nature are far from those which are optimal for industrial processes. In this paper the rationale for intensification will be discussed, as well as the four complementary approaches used today to achieve bioprocess intensification. Two of these four approaches are based on alteration...... of the biocatalyst (either by protein engineering or metabolic engineering), resulting in an extra degree of freedom in the process design. To date, biocatalyst engineering has been developed independently from the conventional process engineering methodology to intensification. Although the integration of these two...

Bioprocesses: Modelling needs for process evaluation and sustainability assessment

DEFF Research Database (Denmark)

Jiménez-Gonzaléz, Concepcion; Woodley, John

2010-01-01

development such that they can also be used to evaluate processes against sustainability metrics, as well as economics as an integral part of assessments. Finally, property models will also be required based on compounds not currently present in existing databases. It is clear that many new opportunities......The next generation of process engineers will face a new set of challenges, with the need to devise new bioprocesses, with high selectivity for pharmaceutical manufacture, and for lower value chemicals manufacture based on renewable feedstocks. In this paper the current and predicted future roles...... of process system engineering and life cycle inventory and assessment in the design, development and improvement of sustainable bioprocesses are explored. The existing process systems engineering software tools will prove essential to assist this work. However, the existing tools will also require further...

Differences in rates of switchbacks after switching from branded to authorized generic and branded to generic drug products: cohort study

Science.gov (United States)

Sarpatwari, Ameet; Dejene, Sara; Khan, Nazleen F; Lii, Joyce; Rogers, James R; Dutcher, Sarah K; Raofi, Saeid; Bohn, Justin; Connolly, John; Fischer, Michael A; Kesselheim, Aaron S; Gagne, Joshua J

2018-01-01

Abstract Objectives To compare rates of switchbacks to branded drug products for patients switched from branded to authorized generic drug products, which have the same active ingredients, appearance, and excipients as the branded product, with patients switched from branded to generic drug products, which have the same active ingredients as the branded product but may differ in appearance and excipients. Design Observational cohort study. Setting Private (a large commercial health plan) and public (Medicaid) insurance programs in the US. Participants Beneficiaries of a large US commercial health insurer between 2004 and 2013 (primary cohort) and Medicaid beneficiaries between 2000 and 2010 (replication cohort). Main outcome measures Patients taking branded products for one of the study drugs (alendronate tablets, amlodipine tablets, amlodipine-benazepril capsules, calcitonin salmon nasal spray, escitalopram tablets, glipizide extended release tablets, quinapril tablets, and sertraline tablets) were identified when they switched to an authorized generic or a generic drug product after the date of market entry of generic drug products. These patients were followed for switchbacks to the branded drug product in the year after their switch to an authorized generic or a generic drug product. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals after adjusting for demographics, including age, sex, and calendar year. Inverse variance meta-analysis was used to pool adjusted hazard ratios across all drug products. Results A total of 94 909 patients switched from branded to authorized generic drug products and 116 017 patients switched from branded to generic drug products and contributed to the switchback analysis. Unadjusted incidence rates of switchback varied across drug products, ranging from a low of 3.8 per 100 person years (for alendronate tablets) to a high of 17.8 per 100 person years (for amlodipine

Membrane Bioprocesses for Pharmaceutical Micropollutant Removal from Waters

Directory of Open Access Journals (Sweden)

Matthias de Cazes

2014-10-01

Full Text Available The purpose of this review work is to give an overview of the research reported on bioprocesses for the treatment of domestic or industrial wastewaters (WW containing pharmaceuticals. Conventional WW treatment technologies are not efficient enough to completely remove all pharmaceuticals from water. Indeed, these compounds are becoming an actual public health problem, because they are more and more present in underground and even in potable waters. Different types of bioprocesses are described in this work: from classical activated sludge systems, which allow the depletion of pharmaceuticals by bio-degradation and adsorption, to enzymatic reactions, which are more focused on the treatment of WW containing a relatively high content of pharmaceuticals and less organic carbon pollution than classical WW. Different aspects concerning the advantages of membrane bioreactors for pharmaceuticals removal are discussed, as well as the more recent studies on enzymatic membrane reactors to the depletion of these recalcitrant compounds.

Development of bioprocess for high density cultivation yield of the probiotic Bacillus coagulans and its spores

Directory of Open Access Journals (Sweden)

Kavita R. Pandey

2016-09-01

Full Text Available Bacillus coagulans is a spore forming lactic acid bacterium. Spore forming bacteria, have been extensively studied and commercialized as probiotics. Probiotics are produced by fermentation technology. There is a limitation to biomass produced by conventional modes of fermentation. With the great demand generated by range of probiotic products, biomass is becoming very valuable for several pharmaceutical, dairy and probiotic companies. Thus, there is a need to develop high cell density cultivation processes for enhanced biomass accumulation. The bioprocess development was carried out in 6.6 L bench top lab scale fermentor. Four different cultivation strategies were employed to develop a bioprocess for higher growth and sporulation efficiencies of probiotic B. coagulans. Batch fermentation of B. coagulans yielded 18 g L-1 biomass (as against 8.0 g L-1 productivity in shake flask with 60% spore efficiency. Fed-batch cultivation was carried out for glucose, which yielded 25 g L-1 of biomass. C/N ratio was very crucial in achieving higher spore titres. Maximum biomass yield recorded was 30 g L-1, corresponding to 3.8 × 1011 cells mL-1 with 81% of cells in sporulated stage. The yield represents increment of 85 times the productivity and 158 times the spore titres relative to the highest reported values for high density cultivation of B. coagulans.

Synthesis and characterization of robust magnetic carriers for bioprocess applications

Energy Technology Data Exchange (ETDEWEB)

Kopp, Willian, E-mail: willkopp@gmail.com [Federal University of São Carlos-UFSCar, Graduate Program in Chemical Engineering, Rodovia Washington Luiz, km 235, São Carlos, São Paulo 13565-905 (Brazil); Silva, Felipe A., E-mail: eq.felipe.silva@gmail.com [Federal University of São Carlos-UFSCar, Graduate Program in Chemical Engineering, Rodovia Washington Luiz, km 235, São Carlos, São Paulo 13565-905 (Brazil); Lima, Lionete N., E-mail: lionetenunes@yahoo.com.br [Federal University of São Carlos-UFSCar, Graduate Program in Chemical Engineering, Rodovia Washington Luiz, km 235, São Carlos, São Paulo 13565-905 (Brazil); Masunaga, Sueli H., E-mail: sueli.masunaga@gmail.com [Department of Physics, Montana State University-MSU, 173840, Bozeman, MT 59717-3840 (United States); Tardioli, Paulo W., E-mail: pwtardioli@ufscar.br [Department of Chemical Engineering, Federal University of São Carlos-UFSCar, Rodovia Washington Luiz, km 235, São Carlos, São Paulo 13565-905 (Brazil); Giordano, Roberto C., E-mail: roberto@ufscar.br [Department of Chemical Engineering, Federal University of São Carlos-UFSCar, Rodovia Washington Luiz, km 235, São Carlos, São Paulo 13565-905 (Brazil); Araújo-Moreira, Fernando M., E-mail: faraujo@df.ufscar.br [Department of Physics, Federal University of São Carlos-UFSCar, Rodovia Washington Luiz, km 235, São Carlos, São Paulo 13565-905 (Brazil); and others

2015-03-15

Highlights: • Silica magnetic microparticles were synthesized for applications in bioprocesses. • The process to produce magnetic microparticles is inexpensive and easily scalable. • Microparticles with very high saturation magnetization were obtained. • The structure of the silica magnetic microparticles could be controlled. - Abstract: Magnetic carriers are an effective option to withdraw selected target molecules from complex mixtures or to immobilize enzymes. This paper describes the synthesis of robust silica magnetic microparticles (SMMps), particularly designed for applications in bioprocesses. SMMps were synthesized in a micro-emulsion, using sodium silicate as the silica source and superparamagnetic iron oxide nanoparticles as the magnetic core. Thermally resistant particles, with high and accessible surface area, narrow particle size distribution, high saturation magnetization, and with superparamagnetic properties were obtained. Several reaction conditions were tested, yielding materials with saturation magnetization between 45 and 63 emu g{sup −1}, particle size between 2 and 200 μm and average diameter between 11.2 and 15.9 μm, surface area between 49 and 103 m{sup 2} g{sup −1} and pore diameter between 2 and 60 nm. The performance of SMMps in a bioprocess was evaluated by the immobilization of Pseudomonas fluorescens lipase on to octyl modified SMMp, the biocatalyst obtained was used in the production of butyl butyrate with good results.

Bioprocessing of sewage sludge for safe recycling on agricultural land - BIOWASTE

Energy Technology Data Exchange (ETDEWEB)

Schmidt, Jens Ejbye; Angelidaki, Irini; Christensen, Nina; Batstone, Damien John; Lyberatos, Gerasimos; Stamatelatou, Katerina; Lichtfouse, Eric; Elbisser, Brigitte; Rogers, Kayne; Sappin-Didier, Valerie; Dernaix, Laurence; Caria; Giovanni; Metzger, Laure; Borghi, Veronica; Montcada, Eloi

2003-07-01

Disposal and handling of sewage sludge are increasing problems in Europe due to the increasing quantities of the sewage sludge produced. A large amount of the sewage sludge contains small fractions of toxic chemicals, which results in problems with safe use of the sewage sludge on agricultural land. From an ecological and economical point of view, it would be essential to establish methodologies, which could allow sewage sludge to be reused as fertilizers on agricultural land. Energy efficient biotreatment processes of organic waste are, therefore, of crucial importance. BIOWASTE will offer an integrated study of this area. The typical composition of sewage sludge will be characterized with regard to key contaminating compounds. The following compounds will be in focus: Emulsifying agents such as nonylphenols and nonylphenol ethoxylates (NPE), polycyclic aromatic hydrocarbons (PAHs) derived from incomplete combustion processes and phthalates, which are used as additives in plastics and surfactants such as linear alkyl benzene sulfonate (LAS). Analytical techniques suitable for qualitative and quantitative evaluation of the chemical species involved in the processes under investigation will be determined. Bacteria that are able to degrade selected contaminating compounds under anaerobic and aerobic conditions will be isolated, characterized and bioaugmented for decontamination of sewage sludge through bioprocessing. Aerobic, anaerobic and combination of aerobic/anaerobic bioprocessing of sewage sludge will be applied. A mathematical model will be developed to describe the biodegradation processes of the contaminating compounds after establishing the kinetic parameters for degradation of contaminating compounds. The bioprocessed sewage sludge will be used in eco- and plant- toxicology tests to evaluate the impact of the xenobiotics on the environment. Methodologies will be developed and applied to assess the cleanliness of the bioprocessing as a safe method for waste

Sense and sensitivity in bioprocessing-detecting cellular metabolites with biosensors.

Science.gov (United States)

Dekker, Linda; Polizzi, Karen M

2017-10-01

Biosensors use biological elements to detect or quantify an analyte of interest. In bioprocessing, biosensors are employed to monitor key metabolites. There are two main types: fully biological systems or biological recognition coupled with physical/chemical detection. New developments in chemical biosensors include multiplexed detection using microfluidics. Synthetic biology can be used to engineer new biological biosensors with improved characteristics. Although there have been few biosensors developed for bioprocessing thus far, emerging trends can be applied in the future. A range of new platform technologies will enable rapid engineering of new biosensors based on transcriptional activation, riboswitches, and Förster Resonance Energy Transfer. However, translation to industry remains a challenge and more research into the robustness biosensors at scale is needed. Copyright © 2017 Elsevier Ltd. All rights reserved.

ECUT (Energy Conversion and Utilization Technologies) program: Biocatalysis project

Science.gov (United States)

Baresi, Larry

1989-03-01

The Annual Report presents the fiscal year (FY) 1988 research activities and accomplishments, for the Biocatalysis Project of the U.S. Department of Energy, Energy Conversion and Utilization Technologies (ECUT) Division. The ECUT Biocatalysis Project is managed by the Jet Propulsion Laboratory, California Institute of Technology. The Biocatalysis Project is a mission-oriented, applied research and exploratory development activity directed toward resolution of the major generic technical barriers that impede the development of biologically catalyzed commercial chemical production. The approach toward achieving project objectives involves an integrated participation of universities, industrial companies and government research laboratories. The Project's technical activities were organized into three work elements: (1) The Molecular Modeling and Applied Genetics work element includes research on modeling of biological systems, developing rigorous methods for the prediction of three-dimensional (tertiary) protein structure from the amino acid sequence (primary structure) for designing new biocatalysis, defining kinetic models of biocatalyst reactivity, and developing genetically engineered solutions to the generic technical barriers that preclude widespread application of biocatalysis. (2) The Bioprocess Engineering work element supports efforts in novel bioreactor concepts that are likely to lead to substantially higher levels of reactor productivity, product yields and lower separation energetics. Results of work within this work element will be used to establish the technical feasibility of critical bioprocess monitoring and control subsystems. (3) The Bioprocess Design and Assessment work element attempts to develop procedures (via user-friendly computer software) for assessing the energy-economics of biocatalyzed chemical production processes, and initiation of technology transfer for advanced bioprocesses.

Design of digital learning material for bioprocess-engineering-education

NARCIS (Netherlands)

Schaaf, van der H.

2007-01-01

With the advance of computers and the internet, new types of learning material can be developed: web-based digital learning material. Because many complex learning objectives in the food- and bioprocess technology domain are difficult to achieve in a traditional learning environment, a project was

Therapeutic antibodies: market considerations, disease targets and bioprocessing.

Science.gov (United States)

Elvin, John G; Couston, Ruairidh G; van der Walle, Christopher F

2013-01-02

Antibodies are well established in mainstream clinical practice and present an exciting area for collaborative research and development in industry and academia alike. In this review, we will provide an overview of the current market and an outlook to 2015, focussing on whole antibody molecules while acknowledging the next generation scaffolds containing variable fragments. The market will be discussed in the context of disease targets, particularly in the areas of oncology and immune disorders which generate the greatest revenue by a wide margin. Emerging targets include central nervous system disorders which will also stimulate new delivery strategies. It is becoming increasingly apparent that a better understanding of bioprocessing is required in order to optimize the steps involved in the preparation of a protein prior to formulation. The latter is outside the scope of this review and nor is it our intention to discuss protein delivery and pharmacokinetics. The challenges that lie ahead include the discovery of new disease targets and the development of robust bioprocessing operations. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Generic Reed Solomon Encorder

Directory of Open Access Journals (Sweden)

Petrus Mursanto

2006-11-01

Full Text Available Reed Solomon (RS codes is a mechanism to detect and correct burst of errors in data transmission and storage systems. It provides a solid introduction to foundation mathematical concept of Galois Field algebra and its application. With the development of digital hardware technology, the RS concepts were brought into reality, i.e. the implementation of RS codec chips. This paper presents the development steps of a generic RS encoder using VHDL. The encoder is able to handle generic width of data, variable length of information, number of error as well as variable form of primitive polynomial and generator polynomial used in the system. The design has been implemented for FPGA chip Xilinx XC3S200-5FT256 and has a better performance than commercially available equivalent encoder.

Comparison of generic-to-brand switchback patterns for generic and authorized generic drugs

Science.gov (United States)

Hansen, Richard A.; Qian, Jingjing; Berg, Richard; Linneman, James; Seoane-Vazquez, Enrique; Dutcher, Sarah K.; Raofi, Saeid; Page, C. David; Peissig, Peggy

2018-01-01

Background While generic drugs are therapeutically equivalent to brand drugs, some patients and healthcare providers remain uncertain about whether they produce identical outcomes. Authorized generics, which are identical in formulation to corresponding brand drugs but marketed as a generic, provide a unique post-marketing opportunity to study whether utilization patterns are influenced by perceptions of generic drugs. Objectives To compare generic-to-brand switchback rates between generics and authorized generics. Methods A retrospective cohort study was conducted using claims and electronic health records data from a regional U.S. healthcare system. Ten drugs with authorized generics and generics marketed between 1999 and 2014 were evaluated. Eligible adult patients received a brand drug during the 6 months preceding generic entry, and then switched to a generic or authorized generic. Patients in this cohort were followed for up to 30 months from the index switch date to evaluate occurrence of generic-to-brand switchbacks. Switchback rates were compared between patients on authorized generics versus generics using Kaplan-Meier curves and Cox proportional hazards models, controlling for individual drug effects, age, sex, Charlson comorbidity score, pre-index drug use characteristics, and pre-index healthcare utilization. Results Among 5,542 unique patients that switched from brand-to-generic or brand-to-authorized generic, 264 (4.8%) switched back to the brand drug. Overall switchback rates were similar for authorized generics compared with generics (HR=0.86; 95% CI 0.65-1.15). The likelihood of switchback was higher for alendronate (HR=1.64; 95% CI 1.20-2.23) and simvastatin (HR=1.81; 95% CI 1.30-2.54) and lower for amlodipine (HR=0.27; 95% CI 0.17-0.42) compared with other drugs in the cohort. Conclusions Overall switchback rates were similar between authorized generic and generic drug users, indirectly supporting similar efficacy and tolerability profiles for

Application of agent-based system for bioprocess description and process improvement.

Science.gov (United States)

Gao, Ying; Kipling, Katie; Glassey, Jarka; Willis, Mark; Montague, Gary; Zhou, Yuhong; Titchener-Hooker, Nigel J

2010-01-01

Modeling plays an important role in bioprocess development for design and scale-up. Predictive models can also be used in biopharmaceutical manufacturing to assist decision-making either to maintain process consistency or to identify optimal operating conditions. To predict the whole bioprocess performance, the strong interactions present in a processing sequence must be adequately modeled. Traditionally, bioprocess modeling considers process units separately, which makes it difficult to capture the interactions between units. In this work, a systematic framework is developed to analyze the bioprocesses based on a whole process understanding and considering the interactions between process operations. An agent-based approach is adopted to provide a flexible infrastructure for the necessary integration of process models. This enables the prediction of overall process behavior, which can then be applied during process development or once manufacturing has commenced, in both cases leading to the capacity for fast evaluation of process improvement options. The multi-agent system comprises a process knowledge base, process models, and a group of functional agents. In this system, agent components co-operate with each other in performing their tasks. These include the description of the whole process behavior, evaluating process operating conditions, monitoring of the operating processes, predicting critical process performance, and providing guidance to decision-making when coping with process deviations. During process development, the system can be used to evaluate the design space for process operation. During manufacture, the system can be applied to identify abnormal process operation events and then to provide suggestions as to how best to cope with the deviations. In all cases, the function of the system is to ensure an efficient manufacturing process. The implementation of the agent-based approach is illustrated via selected application scenarios, which

Systematic Development of Miniaturized (Bio)Processes using Process Systems Engineering (PSE) Methods and Tools

DEFF Research Database (Denmark)

Krühne, Ulrich; Larsson, Hilde; Heintz, Søren

2014-01-01

The focus of this work is on process systems engineering (PSE) methods and tools, and especially on how such PSE methods and tools can be used to accelerate and support systematic bioprocess development at a miniature scale. After a short presentation of the PSE methods and the bioprocess...... development drivers, three case studies are presented. In the first example it is demonstrated how experimental investigations of the bi-enzymatic production of lactobionic acid can be modeled with help of a new mechanistic mathematical model. The reaction was performed at lab scale and the prediction quality...

Advances in Consolidated Bioprocessing Using Clostridium thermocellum and Thermoanaerobacter saccharolyticum

Energy Technology Data Exchange (ETDEWEB)

Lynd, Lee R. [Dartmouth College, Thayer School of Engineering; Guss, Adam M. [ORNL; Himmel, Mike [National Renewable Energy Laboratory (NREL); Beri, Dhananjay [Dartmouth College, Thayer School of Engineering; Herring, Christopher [Mascoma Corporation; Holwerda, Evert [Dartmouth College, Thayer School of Engineering; Murphy, Sean J. [Dartmouth College, Thayer School of Engineering; Olson, Daniel G. [Dartmouth College, Thayer School of Engineering; Paye, Julie [Dartmouth College, Thayer School of Engineering; Rydzak, Thomas [ORNL; Shao, Xiongjun [Dartmouth College, Thayer School of Engineering; Tian, Liang [Dartmouth College, Thayer School of Engineering; Worthen, Robert [Dartmouth College, Thayer School of Engineering

2016-11-01

Recent advances are addressed pertaining to consolidated bioprocessing (CBP) of plant cell walls to ethanol using two thermophilic, saccharolytic bacteria: the cellulose-fermenting Clostridium thermocellum and the hemicellulose- fermenting ermoanaerobacterium saccharolyticum. On the basis of the largest comparative dataset assembled to date, it appears that C. thermocellum is substantially more effective at solubilizing unpretreated plant cell walls than industry-standard fungal cellulase, and that this is particularly the case for more recalcitrant feedstocks. e distinctive central metabolism of C. thermocellum appears to involve more extensive energy coupling (e.g., on the order of 5 ATP per glucosyl moiety) than most fermentative anaerobes. Ethanol yields and titers realized by engineered strains of T. saccharolyticum meet standards for industrial feasibility and provide an important proof of concept as well as a model that may be emulated in other organisms. Progress has also been made with C. thermocellum, although not yet to this extent. e current state of strain development is summarized and outstanding challenges for commercial application are discussed. We speculate that CBP organism development is more promising starting with naturally occurring cellulolytic microbes as compared to starting with noncellulolytic hosts.

Restructuring upstream bioprocessing: technological and economical aspects for production of a generic microbial feedstock from wheat.

Science.gov (United States)

Koutinas, A A; Wang, R; Webb, C

2004-03-05

Restructuring and optimization of the conventional fermentation industry for fuel and chemical production is necessary to replace petrochemical production routes. Guided by this concept, a novel biorefinery process has been developed as an alternative to conventional upstream processing routes, leading to the production of a generic fermentation feedstock from wheat. The robustness of Aspergillus awamori as enzyme producer is exploited in a continuous fungal fermentation on whole wheat flour. Vital gluten is extracted as an added-value byproduct by the conventional Martin process from a fraction of the overall wheat used. Enzymatic hydrolysis of gluten-free flour by the enzyme complex produced by A. awamori during fermentation produces a liquid stream rich in glucose (320 g/L). Autolysis of fungal cells produces a micronutrient-rich solution similar to yeast extract (1.6 g/L nitrogen, 0.5 g/L phosphorus). The case-specific combination of these two liquid streams can provide a nutrient-complete fermentation medium for a spectrum of microbial bioconversions for the production of such chemicals as organic acids, amino acids, bioethanol, glycerol, solvents, and microbial biodegradable plastics. Preliminary economic analysis has shown that the operating cost required to produce the feedstock is dependent on the plant capacity, cereal market price, presence and market value of added-value byproducts, labor costs, and mode of processing (batch or continuous). Integration of this process in an existing fermentation plant could lead to the production of a generic feedstock at an operating cost lower than the market price of glucose syrup (90% to 99% glucose) in the EU, provided that the plant capacity exceeds 410 m(3)/day. Further process improvements are also suggested. Copyright 2004 Wiley Periodicals, Inc.

16 CFR 303.41 - Use of fiber trademarks and generic names in advertising.

Science.gov (United States)

2010-01-01

... use of a fiber trademark shall require a full disclosure of the fiber content information required by... or generic name is used in non-required information in advertising, such fiber trademark or generic... advertising. 303.41 Section 303.41 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC...

Pharmaceutical Equivalence of Some Commercial Samples of ...

African Journals Online (AJOL)

Purpose: To study the physical properties and dissolution profiles of commercial samples of artesunate and amodiaquine tablets. Methods: Fifteen generic brands of artesunate and five generic brands of amodiaquine tablets were obtained from drug retail outlets in Oyo and Ogun States in southwestern Nigeria. The tablets ...

Comparison of Generic-to-Brand Switchback Rates Between Generic and Authorized Generic Drugs.

Science.gov (United States)

Hansen, Richard A; Qian, Jingjing; Berg, Richard; Linneman, James; Seoane-Vazquez, Enrique; Dutcher, Sarah K; Raofi, Saeid; Page, C David; Peissig, Peggy

2017-04-01

Generic drugs contain identical active ingredients as their corresponding brand drugs and are pharmaceutically equivalent and bioequivalent, whereas authorized generic drugs (AGs) contain both identical active and inactive ingredients as their corresponding brand drugs but are marketed as generics. This study compares generic-to-brand switchback rates between generic and AGs. Retrospective cohort study. Claims and electronic health record data from a regional U.S. health care system. The full cohort consisted of 5542 unique patients who received select branded drugs during the 6 months prior to their generic drug market availability (between 1999 and 2014) and then were switched to an AG or generic drug within 30 months of generic drug entry. For these patients, 5929 unique patient-drug combinations (867 with AGs and 5062 with generic drugs) were evaluated. Ten drugs with AGs and generics marketed between 1999 and 2014 were evaluated. The date of the first generic prescription was considered the index date for each drug, and it marked the beginning of follow-up to evaluate the occurrence of generic-to-brand switchback patterns over the subsequent 30 months. Switchback rates were compared between patients receiving AGs versus those receiving generics using multivariable Cox proportional hazards models, controlling for individual drug effects, age, sex, Charlson Comorbidity Score, pre-index drug use characteristics, and pre-index health care utilization. Among the 5542 unique patients who switched from brand to generic or brand to AG, 264 (4.8%) switched back to the brand drug. Overall switchback rates were similar for AGs compared with generics (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.65-1.15). The likelihood of switchback was higher for alendronate (HR 1.64, 95% CI 1.20-2.23) and simvastatin (HR 1.81, 95% CI 1.30-2.54) and lower for amlodipine (HR 0.27, 95% CI 0.17-0.42) compared with the other drugs evaluated. Overall switchback rates were similar

Bioprocessing papaya processing waste for potential aquaculture feed supplement--economic and nutrient analysis with shrimp feeding trial.

Science.gov (United States)

Kang, H Y; Yang, P Y; Dominy, W G; Lee, C S

2010-10-01

Papaya processing waste (PPW), a major fruit processing waste in the Hawaii islands, served as substrate for yeast (Saccharomyces cerevisiae) growth. The fermented PPW products containing nutrients of 45% crude protein and various fat, fiber, lignin, cellulose, and minerals were advantages to nutrients of yeast alone. Three experimental diets controlled at 35% protein formulation containing different levels of inclusion of PPW products and a commercial control diet were fed to shrimps for 8 weeks. The 50% inclusion of PPW diets were comparable to commercial feed in weight, growth, feed conversion ratio (FCR) and survival rate. Such bioprocess treatment system would be economically feasible with the control of annual cost and increase of the amount of PPW treated. The selling price of PPW products and annual operation and maintenance cost were the most influential factors to additional profits. This study presented a promising alternative for environmental-friendly treatment of organic wastes as well as the sustainability of local agriculture and aquaculture industries. Copyright © 2010 Elsevier Ltd. All rights reserved.

HEK293 cell culture media study towards bioprocess optimization: Animal derived component free and animal derived component containing platforms.

Science.gov (United States)

Liste-Calleja, Leticia; Lecina, Martí; Cairó, Jordi Joan

2014-04-01

The increasing demand for biopharmaceuticals produced in mammalian cells has lead industries to enhance bioprocess volumetric productivity through different strategies. Among those strategies, cell culture media development is of major interest. In the present work, several commercially available culture media for Human Embryonic Kidney cells (HEK293) were evaluated in terms of maximal specific growth rate and maximal viable cell concentration supported. The main objective was to provide different cell culture platforms which are suitable for a wide range of applications depending on the type and the final use of the product obtained. Performing simple media supplementations with and without animal derived components, an enhancement of cell concentration from 2 × 10(6) cell/mL to 17 × 10(6) cell/mL was achieved in batch mode operation. Additionally, the media were evaluated for adenovirus production as a specific application case of HEK293 cells. None of the supplements interfered significantly with the adenovirus infection although some differences were encountered in viral productivity. To the best of our knowledge, the high cell density achieved in the work presented has never been reported before in HEK293 batch cell cultures and thus, our results are greatly promising to further study cell culture strategies in bioreactor towards bioprocess optimization. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Production-process optimization algorithm: Application to fed-batch bioprocess

Czech Academy of Sciences Publication Activity Database

Pčolka, M.; Čelikovský, Sergej

2017-01-01

Roč. 354, č. 18 (2017), s. 8529-8551 ISSN 0016-0032 R&D Projects: GA ČR(CZ) GA17-04682S Institutional support: RVO:67985556 Keywords : Optimal control * Bioprocess * Optimization Subject RIV: BC - Control Systems Theory OBOR OECD: Automation and control systems Impact factor: 3.139, year: 2016 https://doi.org/10.1016/j.jfranklin.2017.10.012

40 CFR 721.10006 - Mixed metal oxide (generic).

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Mixed metal oxide (generic). 721.10006 Section 721.10006 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES...) of this section. (2) The significant new uses are: (i) Industrial, commercial, and consumer...

40 CFR 721.10163 - Chloro fluoro alkane (generic).

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Chloro fluoro alkane (generic). 721.10163 Section 721.10163 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC...)(2) of this section. (2) The significant new uses are: (i) Industrial, commercial, and consumer...

40 CFR 721.9079 - Dihydro quinacridone derivative (generic).

Science.gov (United States)

2010-07-01

...) Industrial, commercial, and consumer activities. Requirements as specified in § 721.80(s) (1,000 kg). (ii... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Dihydro quinacridone derivative (generic). 721.9079 Section 721.9079 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...

Cell bioprocessing in space - Applications of analytical cytology

Science.gov (United States)

Todd, P.; Hymer, W. C.; Goolsby, C. L.; Hatfield, J. M.; Morrison, D. R.

1988-01-01

Cell bioprocessing experiments in space are reviewed and the development of on-board cell analytical cytology techniques that can serve such experiments is discussed. Methods and results of experiments involving the cultivation and separation of eukaryotic cells in space are presented. It is suggested that an advanced cytometer should be developed for the quantitative analysis of large numbers of specimens of suspended eukaryotic cells and bioparticles in experiments on the Space Station.

40 CFR 721.10003 - Manganese heterocyclic tetraamine complex (generic).

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Manganese heterocyclic tetraamine complex (generic). 721.10003 Section 721.10003 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... section. (2) The significant new uses are: (i) Industrial, commercial, and consumer activities...

40 CFR 721.10132 - Phosphoramidic acid, carbomonocyclic-, diphenylester (generic).

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Phosphoramidic acid, carbomonocyclic-, diphenylester (generic). 721.10132 Section 721.10132 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... significant new uses are: (i) Industrial, commercial, and consumer activities. Requirements as specified in...

40 CFR 721.10087 - Substituted alkyl phosphine oxide (generic).

Science.gov (United States)

2010-07-01

... are: (i) Industrial, commercial, and consumer activities. Requirements as specified in § 721.80(s... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted alkyl phosphine oxide (generic). 721.10087 Section 721.10087 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED...

Method for developing cost estimates for generic regulatory requirements

International Nuclear Information System (INIS)

1985-01-01

The NRC has established a practice of performing regulatory analyses, reflecting costs as well as benefits, of proposed new or revised generic requirements. A method had been developed to assist the NRC in preparing the types of cost estimates required for this purpose and for assigning priorities in the resolution of generic safety issues. The cost of a generic requirement is defined as the net present value of total lifetime cost incurred by the public, industry, and government in implementing the requirement for all affected plants. The method described here is for commercial light-water-reactor power plants. Estimating the cost for a generic requirement involves several steps: (1) identifying the activities that must be carried out to fully implement the requirement, (2) defining the work packages associated with the major activities, (3) identifying the individual elements of cost for each work package, (4) estimating the magnitude of each cost element, (5) aggregating individual plant costs over the plant lifetime, and (6) aggregating all plant costs and generic costs to produce a total, national, present value of lifetime cost for the requirement. The method developed addresses all six steps. In this paper, we discuss on the first three

Bioprocessing of ores: Application to space resources

Science.gov (United States)

Johansson, Karl R.

1992-01-01

The role of microorganisms in the oxidation and leaching of various ores (especially those of copper, iron, and uranium) is well known. This role is increasingly being applied by the mining, metallurgy, and sewage industries in the bioconcentration of metal ions from natural receiving waters and from waste waters. It is concluded that bioprocessing using bacteria in closed reactors may be a variable option for the recovery of metals from the lunar regolith. Obviously, considerable research must be done to define the process, specify the appropriate bacteria, determine the necessary conditions and limitations, and evaluate the overall feasibility.

Bioprocessing of wheat bran in whole wheat bread increases the bioavailability of phenolic acids in men and exerts antiinflammatory effects ex vivo.

Science.gov (United States)

Mateo Anson, Nuria; Aura, Anna-Marja; Selinheimo, Emilia; Mattila, Ismo; Poutanen, Kaisa; van den Berg, Robin; Havenaar, Robert; Bast, Aalt; Haenen, Guido R M M

2011-01-01

Whole grain consumption has been linked to a lower risk of metabolic syndrome, which is normally associated with a low-grade chronic inflammation. The benefits of whole grain are in part related to the inclusion of the bran, rich in phenolic acids and fiber. However, the phenols are poorly bioaccessible from the cereal matrix. The aim of the present study was to investigate the effect of bioprocessing of the bran in whole wheat bread on the bioavailability of phenolic acids, the postprandial plasma antioxidant capacity, and ex vivo antiinflammatory properties. After consumption of a low phenolic acid diet for 3 d and overnight fasting, 8 healthy men consumed 300 g of whole wheat bread containing native bran (control bread) or bioprocessed bran (bioprocessed bread) in a cross-over design. Urine and blood samples were collected for 24 h to analyze the phenolic acids and metabolites. Trolox equivalent antioxidant capacity was measured in plasma. Cytokines were measured in blood after ex vivo stimulation with LPS. The bioavailabilities of ferulic acid, vanillic acid, sinapic acid, and 3,4-dimethoxybenzoic acid from the bioprocessed bread were 2- to 3-fold those from the control bread. Phenylpropionic acid and 3-hydroxyphenylpropionic acid were the main colonic metabolites of the nonbioaccessible phenols. The ratios of pro-:antiinflammatory cytokines were significantly lower in LPS-stimulated blood after the consumption of the bioprocessed bread. In conclusion, bioprocessing can remarkably increase the bioavailability of phenolic acids and their circulating metabolites, compounds which have immunomodulatory effects ex vivo.

Generic antibiotic industries: Challenges and implied strategies with regulatory perspectives

Directory of Open Access Journals (Sweden)

M Venkatesh

2011-01-01

Full Text Available Ever since the discovery of antibiotics, the quality of human life greatly improved in the 20 th century. The discovery of penicillin transformed the medicine industry and initiated a search for a better antibiotic every time resulting in several synthetic and semi-synthetic antibiotics. Beginning with the 1937 sulfa drug tragedy, the drug regulations had a parallel growth along with the antibiotics and the antibiotic-based generic Pharma industries. This review article is focused on the scenario depicting current global Pharma industries based on generic antibiotics. Several regulatory aspects involved with these industries have been discussed along with the complexity of the market, issues that could affect their growth, their struggle for quality, and their compliance with the tightened regulations. With the skyrocketing commercialization of antibiotics through generics and the leveraging technologic renaissance, generic industries are involved in providing maximum safer benefits for the welfare of the people, highlighting its need today.

Generic antibiotic industries: Challenges and implied strategies with regulatory perspectives

Science.gov (United States)

Venkatesh, M.; Bairavi, V. G.; Sasikumar, K. C.

2011-01-01

Ever since the discovery of antibiotics, the quality of human life greatly improved in the 20th century. The discovery of penicillin transformed the medicine industry and initiated a search for a better antibiotic every time resulting in several synthetic and semi-synthetic antibiotics. Beginning with the 1937 sulfa drug tragedy, the drug regulations had a parallel growth along with the antibiotics and the antibiotic-based generic Pharma industries. This review article is focused on the scenario depicting current global Pharma industries based on generic antibiotics. Several regulatory aspects involved with these industries have been discussed along with the complexity of the market, issues that could affect their growth, their struggle for quality, and their compliance with the tightened regulations. With the skyrocketing commercialization of antibiotics through generics and the leveraging technologic renaissance, generic industries are involved in providing maximum safer benefits for the welfare of the people, highlighting its need today.. PMID:21430959

Bio-Refineries Bioprocess Technologies for Waste-Water Treatment, Energy and Product Valorization

Science.gov (United States)

Keith Cowan, A.

2010-04-01

Increasing pressure is being exerted on communities and nations to source energy from forms other than fossil fuels. Also, potable water is becoming a scarce resource in many parts of the world, and there remains a large divide in the demand and utilization of plant products derived from genetically modified organisms (GMOs) and non-GMOs. The most extensive user and manager of terrestrial ecosystems is agriculture which is also the de facto steward of natural resources. As stated by Miller (2008) no other industry or institution comes close to the comparative advantage held for this vital responsibility while simultaneously providing food, fiber, and other biology-based products, including energy. Since modern commercial agriculture is transitioning from the production of bulk commodities to the provision of standardized products and specific-attribute raw materials for differentiated markets, we can argue that processes such as mass cultivation of microalgae and the concept of bio-refineries be seen as part of a `new' agronomy. EBRU is currently exploring the integration of bioprocess technologies using microalgae as biocatalysts to achieve waste-water treatment, water polishing and endocrine disruptor (EDC) removal, sustainable energy production, and exploitation of the resultant biomass in agriculture as foliar fertilizer and seed coatings, and for commercial extraction of bulk commodities such as bio-oils and lecithin. This presentation will address efforts to establish a fully operational solar-driven microalgae bio-refinery for use not only in waste remediation but to transform waste and biomass to energy, fuels, and other useful materials (valorisation), with particular focus on environmental quality and sustainability goals.

Aspects of modelling and control of bioprocesses

Energy Technology Data Exchange (ETDEWEB)

Zhang, Xiachang

1995-12-31

The modelling and control of bioprocesses are the main subjects in this thesis. Different modelling approaches are proposed for different purposes in various bioprocesses. A conventional global model was constructed for a very complex mammalian cell culture process. A new concept of functional state and a multiple model (local models) approach were used for modelling the fed-batch baker`s yeast process for monitoring and control purposes. Finally, a combination of conventional electrical and biological models was used to simulate and to control a microbial fuel cell process. In the thesis, a yeast growth process was taken as an example to demonstrate the usefulness of the functional state concept and local models. The functional states were first defined according to the yeast metabolism. The process was then described by a set of simple local models. In different functional states, different local models were used. On the other hand, the on-line estimation of functional state and biomass of the process was discussed for process control purpose. As a consequence, both the functional state concept and the multiple model approach were applied for fuzzy logic control of yeast growth process. A fuzzy factor was calculated on the basis of a knowledge-based expert system and fuzzy logic rules. The factor was used to correct an ideal substrate feed rate. In the last part of the thesis, microbial fuel cell processes were studied. A microbial fuel cell is a device for direct conversion of chemical energy to electrical energy by using micro-organisms as catalysts. A combined model including conventional electrical and biological models was constructed for the process based on the biological and electrochemical phenomena

Aspects of modelling and control of bioprocesses

Energy Technology Data Exchange (ETDEWEB)

Zhang, Xiachang

1996-12-31

The modelling and control of bioprocesses are the main subjects in this thesis. Different modelling approaches are proposed for different purposes in various bioprocesses. A conventional global model was constructed for a very complex mammalian cell culture process. A new concept of functional state and a multiple model (local models) approach were used for modelling the fed-batch baker`s yeast process for monitoring and control purposes. Finally, a combination of conventional electrical and biological models was used to simulate and to control a microbial fuel cell process. In the thesis, a yeast growth process was taken as an example to demonstrate the usefulness of the functional state concept and local models. The functional states were first defined according to the yeast metabolism. The process was then described by a set of simple local models. In different functional states, different local models were used. On the other hand, the on-line estimation of functional state and biomass of the process was discussed for process control purpose. As a consequence, both the functional state concept and the multiple model approach were applied for fuzzy logic control of yeast growth process. A fuzzy factor was calculated on the basis of a knowledge-based expert system and fuzzy logic rules. The factor was used to correct an ideal substrate feed rate. In the last part of the thesis, microbial fuel cell processes were studied. A microbial fuel cell is a device for direct conversion of chemical energy to electrical energy by using micro-organisms as catalysts. A combined model including conventional electrical and biological models was constructed for the process based on the biological and electrochemical phenomena

Hybrid elementary flux analysis/nonparametric modeling: application for bioprocess control

Directory of Open Access Journals (Sweden)

Alves Paula M

2007-01-01

Full Text Available Abstract Background The progress in the "-omic" sciences has allowed a deeper knowledge on many biological systems with industrial interest. This knowledge is still rarely used for advanced bioprocess monitoring and control at the bioreactor level. In this work, a bioprocess control method is presented, which is designed on the basis of the metabolic network of the organism under consideration. The bioprocess dynamics are formulated using hybrid rigorous/data driven systems and its inherent structure is defined by the metabolism elementary modes. Results The metabolic network of the system under study is decomposed into elementary modes (EMs, which are the simplest paths able to operate coherently in steady-state. A reduced reaction mechanism in the form of simplified reactions connecting substrates with end-products is obtained. A dynamical hybrid system integrating material balance equations, EMs reactions stoichiometry and kinetics was formulated. EMs kinetics were defined as the product of two terms: a mechanistic/empirical known term and an unknown term that must be identified from data, in a process optimisation perspective. This approach allows the quantification of fluxes carried by individual elementary modes which is of great help to identify dominant pathways as a function of environmental conditions. The methodology was employed to analyse experimental data of recombinant Baby Hamster Kidney (BHK-21A cultures producing a recombinant fusion glycoprotein. The identified EMs kinetics demonstrated typical glucose and glutamine metabolic responses during cell growth and IgG1-IL2 synthesis. Finally, an online optimisation study was conducted in which the optimal feeding strategies of glucose and glutamine were calculated after re-estimation of model parameters at each sampling time. An improvement in the final product concentration was obtained as a result of this online optimisation. Conclusion The main contribution of this work is a

Contributions of depth filter components to protein adsorption in bioprocessing.

Science.gov (United States)

Khanal, Ohnmar; Singh, Nripen; Traylor, Steven J; Xu, Xuankuo; Ghose, Sanchayita; Li, Zheng J; Lenhoff, Abraham M

2018-04-16

Depth filtration is widely used in downstream bioprocessing to remove particulate contaminants via depth straining and is therefore applied to harvest clarification and other processing steps. However, depth filtration also removes proteins via adsorption, which can contribute variously to impurity clearance and to reduction in product yield. The adsorption may occur on the different components of the depth filter, that is, filter aid, binder, and cellulose filter. We measured adsorption of several model proteins and therapeutic proteins onto filter aids, cellulose, and commercial depth filters at pH 5-8 and ionic strengths filter component in the adsorption of proteins with different net charges, using confocal microscopy. Our findings show that a complete depth filter's maximum adsorptive capacity for proteins can be estimated by its protein monolayer coverage values, which are of order mg/m 2 , depending on the protein size. Furthermore, the extent of adsorption of different proteins appears to depend on the nature of the resin binder and its extent of coating over the depth filter surface, particularly in masking the cation-exchanger-like capacity of the siliceous filter aids. In addition to guiding improved depth filter selection, the findings can be leveraged in inspiring a more intentional selection of components and design of depth filter construction for particular impurity removal targets. © 2018 Wiley Periodicals, Inc.

Bioprocessing of lignite coals using reductive microorganisms

Energy Technology Data Exchange (ETDEWEB)

Crawford, D.L.

1992-03-29

In order to convert lignite coals into liquid fuels, gases or chemical feedstock, the macromolecular structure of the coal must be broken down into low molecular weight fractions prior to further modification. Our research focused on this aspect of coal bioprocessing. We isolated, characterized and studied the lignite coal-depolymerizing organisms Streptomyces viridosporus T7A, Pseudomonas sp. DLC-62, unidentified bacterial strain DLC-BB2 and Gram-positive Bacillus megaterium strain DLC-21. In this research we showed that these bacteria are able to solubilize and depolymerize lignite coals using a combination of biological mechanisms including the excretion of coal solublizing basic chemical metabolites and extracellular coal depolymerizing enzymes.

Design-for-Six-Sigma To Develop a Bioprocess Knowledge Management Framework.

Science.gov (United States)

Junker, Beth; Maheshwari, Gargi; Ranheim, Todd; Altaras, Nedim; Stankevicz, Michael; Harmon, Lori; Rios, Sandra; D'anjou, Marc

2011-01-01

Owing to the high costs associated with biopharmaceutical development, considerable pressure has developed for the biopharmaceutical industry to increase productivity by becoming more lean and flexible. The ability to reuse knowledge was identified as one key advantage to streamline productivity, efficiently use resources, and ultimately perform better than the competition. A knowledge management (KM) strategy was assembled for bioprocess-related information using the technique of Design-for-Six-Sigma (DFSS). This strategy supported quality-by-design and process validation efforts for pipeline as well as licensed products. The DFSS technique was selected because it was both streamlined and efficient. These characteristics permitted development of a KM strategy with minimized team leader and team member resources. DFSS also placed a high emphasis on the voice of the customer, information considered crucial to the selection of solutions most appropriate for the current knowledge-based challenges of the organization. The KM strategy developed was comprised of nine workstreams, constructed from related solution buckets which in turn were assembled from the individual solution tasks that were identified. Each workstream's detailed design was evaluated against published and established best practices, as well as the KM strategy project charter and design inputs. Gaps and risks were identified and mitigated as necessary to improve the robustness of the proposed strategy. Aggregated resources (specifically expense/capital funds and staff) and timing were estimated to obtain vital management sponsorship for implementation. Where possible, existing governance and divisional/corporate information technology efforts were leveraged to minimize the additional bioprocess resources required for implementation. Finally, leading and lagging indicator metrics were selected to track the success of pilots and eventual implementation. A knowledge management framework was assembled for

Generic medicines and generic substitution: contrasting perspectives of stakeholders in Ireland.

Science.gov (United States)

O'Leary, A; Usher, C; Lynch, M; Hall, M; Hemeryk, L; Spillane, S; Gallagher, P; Barry, M

2015-12-15

The Health (Pricing and Supply of Medical Goods) Act 2013 passed into law in July 2013 and legislated for generic substitution in Ireland. The aim of the study was to ascertain the knowledge and perceptions of stakeholders i.e. patients, pharmacists and prescribers, of generic medicines and to generic substitution with the passing of legislation. Three stakeholder specific questionnaires were developed to assess knowledge of and perceptions to generic medicines and generic substitution. Purposive samples of patients, prescribers and pharmacists were analysed. Descriptive quantitative and qualitative analyses were undertaken. A total of 762 healthcare professionals and 353 patients were recruited. The study highlighted that over 84% of patients were familiar with generic medicines and are supportive of the concept of generic substitution. Approximately 74% of prescribers and 84% of pharmacists were supportive of generic substitution in most cases. The main areas of concern highlighted by the healthcare professionals that might impact on the successful implementation of the policy, were the issue of bioequivalence with generic medicines, the computer software systems used at present in general practitioner (GP) surgeries and the availability of branded generics. The findings from this study identify a high baseline rate of acceptance to generic medicines and generic substitution among patients, prescribers and pharmacists in the Irish setting. The concerns of the main stakeholders provide a valuable insight into the potential difficulties that may arise in its implementation, and the need for on-going reassurance and proactive dissemination of the impact of the generic substitution policy. The existing positive attitude to generic medicines and generic substitution among key stakeholders in Ireland to generic substitution, combined with appropriate support and collaboration should result in the desired increase in rates of prescribing, dispensing and use of generic

Implementation of draft IEC Generic Model of Type 1 Wind Turbine Generator in PowerFactory and Simulink

DEFF Research Database (Denmark)

Zhao, Haoran; Wu, Qiuwei; Sørensen, Poul Ejnar

2013-01-01

This paper presents the implementation work of IEC generic model of Type 1 wind turbine generator (WTG) in two commercial simulation tools: DIgSILENT PowerFactory (PF) and Matlab Simulink. The model topology, details of the composite blocks and implementation procedure in PF and Simulink environm......This paper presents the implementation work of IEC generic model of Type 1 wind turbine generator (WTG) in two commercial simulation tools: DIgSILENT PowerFactory (PF) and Matlab Simulink. The model topology, details of the composite blocks and implementation procedure in PF and Simulink...

ADAPTIVE HIGH GAIN OBSERVER EXTENSION AND ITS APPLICATION TO BIOPROCESS MONITORING

Czech Academy of Sciences Publication Activity Database

Čelikovský, Sergej; Torres-Munoz, J. A.; Dominguez-Bocanegra, A. R.

2018-01-01

Roč. 54, č. 1 (2018), s. 155-174 ISSN 0023-5954 Institutional support: RVO:67985556 Keywords : Adaptive observers * nonlinear systems * bioprocess Subject RIV: BC - Control Systems Theory OBOR OECD: Computer sciences, information science, bioinformathics (hardware development to be 2.2, social aspect to be 5.8) Impact factor: 0.379, year: 2016 http://doi.org/10.14736/kyb-2018-1-0155

Effect of Bioprocessing on the In Vitro Colonic Microbial Metabolism of Phenolic Acids from Rye Bran Fortified Breads

DEFF Research Database (Denmark)

Koistinen, Ville M; Nordlund, Emilia; Katina, Kati

2017-01-01

in an in vitro colon model, the metabolites were analyzed using two different methods applying mass spectrometry. While phenolic acids were released more extensively from the bioprocessed bran bread and ferulic acid had consistently higher concentrations in the bread type during fermentation, there were only......Cereal bran is an important source of dietary fiber and bioactive compounds, such as phenolic acids. We aimed to study the phenolic acid metabolism of native and bioprocessed rye bran fortified refined wheat bread and to elucidate the microbial metabolic route of phenolic acids. After incubation...

Perception of the value of generic drugs in São Paulo, Brazil

Directory of Open Access Journals (Sweden)

Elene Paltrinieri Nardi

2016-01-01

Full Text Available Abstract The objective of this study was to assess the perceptions of opinion-leaders, patients and their accompanying family members or carers about generic drugs. Three groups of participants were surveyed: (i 50 customers while they were visiting commercial pharmacies located in São Paulo city, Brazil, (ii 25 patients and 25 companions while they were waiting at the university outpatient clinic, and (iii 50 healthcare opinion-leaders from government, hospitals, health plans, academia, and pharmaceutical companies. The questions explored socio-demographic characteristics and perceptions regarding value attributes of generic drugs compared to brand name drugs. Respondents had an average age of 52 years and 53% were women. Respondents believed generic drugs to be cheaper than brand name drugs (97%, and 31% thought generic drugs to be less effective than brand name drugs. Also, generic drugs were perceived by 54% of respondents to be as safe as brand name drugs and 74% would prefer brand name drugs if there was no price difference. In conclusion, multiple factors may contribute to the decision to buy generic drugs; among these, perceived effectiveness, safety and price appear to be the most important factors.

Perception of the value of generic drugs in São Paulo, Brazil.

Science.gov (United States)

Nardi, Elene Paltrinieri; Ferraz, Marcos Bosi

2016-02-01

The objective of this study was to assess the perceptions of opinion-leaders, patients and their accompanying family members or carers about generic drugs. Three groups of participants were surveyed: (i) 50 customers while they were visiting commercial pharmacies located in São Paulo city, Brazil, (ii) 25 patients and 25 companions while they were waiting at the university outpatient clinic, and (iii) 50 healthcare opinion-leaders from government, hospitals, health plans, academia, and pharmaceutical companies. The questions explored socio-demographic characteristics and perceptions regarding value attributes of generic drugs compared to brand name drugs. Respondents had an average age of 52 years and 53% were women. Respondents believed generic drugs to be cheaper than brand name drugs (97%), and 31% thought generic drugs to be less effective than brand name drugs. Also, generic drugs were perceived by 54% of respondents to be as safe as brand name drugs and 74% would prefer brand name drugs if there was no price difference. In conclusion, multiple factors may contribute to the decision to buy generic drugs; among these, perceived effectiveness, safety and price appear to be the most important factors.

Teaching bioprocess engineering to undergraduates: Multidisciplinary hands-on training in a one-week practical course.

Science.gov (United States)

Henkel, Marius; Zwick, Michaela; Beuker, Janina; Willenbacher, Judit; Baumann, Sandra; Oswald, Florian; Neumann, Anke; Siemann-Herzberg, Martin; Syldatk, Christoph; Hausmann, Rudolf

2015-01-01

Bioprocess engineering is a highly interdisciplinary field of study which is strongly benefited by practical courses where students can actively experience the interconnection between biology, engineering, and physical sciences. This work describes a lab course developed for 2nd year undergraduate students of bioprocess engineering and related disciplines, where students are challenged with a real-life bioprocess-engineering application, the production of recombinant protein in a fed-batch process. The lab course was designed to introduce students to the subject of operating and supervising an experiment in a bioreactor, along with the analysis of collected data and a final critical evaluation of the experiment. To provide visual feedback of the experimental outcome, the organism used during class was Escherichia coli which carried a plasmid to recombinantly produce enhanced green fluorescent protein (eGFP) upon induction. This can easily be visualized in both the bioreactor and samples by using ultraviolet light. The lab course is performed with bioreactors of the simplest design, and is therefore highly flexible, robust and easy to reproduce. As part of this work the implementation and framework, the results, the evaluation and assessment of student learning combined with opinion surveys are presented, which provides a basis for instructors intending to implement a similar lab course at their respective institution. © 2015 by the International Union of Biochemistry and Molecular Biology.

BIOPROCESS DEVELOPMENTS FOR CELLULASE PRODUCTION BY Aspergillus oryzae CULTIVATED UNDER SOLID-STATE FERMENTATION

Directory of Open Access Journals (Sweden)

R. D. P. B. Pirota

Full Text Available Abstract Bioprocess development studies concerning the production of cellulases are of crucial importance due to the significant impact of these enzymes on the economics of biomass conversion into fuels and chemicals. This work evaluates the effects of solid-state fermentation (SSF operational conditions on cellulase production by a novel strain of Aspergillus oryzae using an instrumented lab-scale bioreactor equipped with an on-line automated monitoring and control system. The use of SSF cultivation under controlled conditions substantially improved cellulase production. Highest production of FPase (0.40 IU g-1, endoglucanase (123.64 IU g-1, and β-glucosidase (18.32 IU g-1 was achieved at 28 °C, using an initial substrate moisture content of 70%, with an inlet air humidity of 80% and an airflow rate of 20 mL min-1. Further studies of kinetic profiles and respirometric analyses were performed. The results showed that these data could be very useful for bioprocess development of cellulase production and scale-up.

Capacity Planning for Batch and Perfusion Bioprocesses Across Multiple Biopharmaceutical Facilities

OpenAIRE

Siganporia, Cyrus C; Ghosh, Soumitra; Daszkowski, Thomas; Papageorgiou, Lazaros G; Farid, Suzanne S

2014-01-01

Production planning for biopharmaceutical portfolios becomes more complex when products switch between fed-batch and continuous perfusion culture processes. This article describes the development of a discrete-time mixed integer linear programming (MILP) model to optimize capacity plans for multiple biopharmaceutical products, with either batch or perfusion bioprocesses, across multiple facilities to meet quarterly demands. The model comprised specific features to account for products with fe...

Bioprocessing of wheat bran improves in vitro bioaccessibility and colonic metabolism of phenolic compounds

NARCIS (Netherlands)

Mateo Anson, N.; Selinheimo, E.; Havenaar, R.; Aura, A.-M.; Mattila, I.; Lehtinen, P.; Bast, A.; Poutanen, K.; Haenen, G.R.M.M.

2009-01-01

Ferulic acid (FA) is the most abundant phenolic compound in wheat grain, mainly located in the bran. However, its bioaccessibility from the bran matrix is extremely low. Different bioprocessing techniques involving fermentation or enzymatic and fermentation treatments of wheat bran were developed

Automated measurement and monitoring of bioprocesses: key elements of the M(3)C strategy.

Science.gov (United States)

Sonnleitner, Bernhard

2013-01-01

The state-of-routine monitoring items established in the bioprocess industry as well as some important state-of-the-art methods are briefly described and the potential pitfalls discussed. Among those are physical and chemical variables such as temperature, pressure, weight, volume, mass and volumetric flow rates, pH, redox potential, gas partial pressures in the liquid and molar fractions in the gas phase, infrared spectral analysis of the liquid phase, and calorimetry over an entire reactor. Classical as well as new optical versions are addressed. Biomass and bio-activity monitoring (as opposed to "measurement") via turbidity, permittivity, in situ microscopy, and fluorescence are critically analyzed. Some new(er) instrumental analytical tools, interfaced to bioprocesses, are explained. Among those are chromatographic methods, mass spectrometry, flow and sequential injection analyses, field flow fractionation, capillary electrophoresis, and flow cytometry. This chapter surveys the principles of monitoring rather than compiling instruments.

Pharmaceutical quality of docetaxel generics versus originator drug product: a comparative analysis.

Science.gov (United States)

Vial, Jérôme; Cohen, Mélanie; Sassiat, Patrick; Thiébaut, Didier

2008-07-01

The aim of this study was to evaluate the quality of 31 commercially available generic formulations of docetaxel purchased in 14 countries by comparing their docetaxel content, impurity levels and pH versus those of the proprietary product Taxotere (Tx). Generic formulations were purchased in 14 countries in Asia, Africa, the Middle East and Latin America. Levels of docetaxel and impurities (chromatographic peaks above 0.05%) were obtained for each sample using reverse-phase liquid chromatography with ultraviolet detection. The pH of aqueous solutions of generic docetaxel formulations and Tx was also measured. A global evaluation of quality was conducted on each product using a multicriteria desirability analysis based on standards defined by the International Conference on Harmonisation guidelines and the US Pharmacopeia paclitaxel injection monograph. Most generic formulations contained a lower than expected amount of docetaxel and/or a high level of impurities: 21 generic docetaxel formulations had an average mass of docetaxel that was generic docetaxel formulations had a total impurity content of >3.0%, almost twice the level of impurities in Tx 20 mg. In total, 33 impurities not present in Tx were detected in the generic samples. Desirability analysis demonstrated that none of the generic docetaxel formulations had composition characteristics similar to those of Tx. This study demonstrated that from an analytical point of view, 90% of the generic docetaxel formulations evaluated contained insufficient active drug, high levels of impurities or both. This has the potential to affect both efficacy and safety of the drug.

Allogeneic cell therapy bioprocess economics and optimization: single-use cell expansion technologies.

Science.gov (United States)

Simaria, Ana S; Hassan, Sally; Varadaraju, Hemanthram; Rowley, Jon; Warren, Kim; Vanek, Philip; Farid, Suzanne S

2014-01-01

For allogeneic cell therapies to reach their therapeutic potential, challenges related to achieving scalable and robust manufacturing processes will need to be addressed. A particular challenge is producing lot-sizes capable of meeting commercial demands of up to 10(9) cells/dose for large patient numbers due to the current limitations of expansion technologies. This article describes the application of a decisional tool to identify the most cost-effective expansion technologies for different scales of production as well as current gaps in the technology capabilities for allogeneic cell therapy manufacture. The tool integrates bioprocess economics with optimization to assess the economic competitiveness of planar and microcarrier-based cell expansion technologies. Visualization methods were used to identify the production scales where planar technologies will cease to be cost-effective and where microcarrier-based bioreactors become the only option. The tool outputs also predict that for the industry to be sustainable for high demand scenarios, significant increases will likely be needed in the performance capabilities of microcarrier-based systems. These data are presented using a technology S-curve as well as windows of operation to identify the combination of cell productivities and scale of single-use bioreactors required to meet future lot sizes. The modeling insights can be used to identify where future R&D investment should be focused to improve the performance of the most promising technologies so that they become a robust and scalable option that enables the cell therapy industry reach commercially relevant lot sizes. The tool outputs can facilitate decision-making very early on in development and be used to predict, and better manage, the risk of process changes needed as products proceed through the development pathway. © 2013 Wiley Periodicals, Inc.

Bioprocessing of concentrated mixed hazardous industrial waste

International Nuclear Information System (INIS)

Wolfram, J.H.; Rogers, R.D.; Silver, G.; Attalla, A.; Prisc, M.

1994-01-01

The use of selected microorganisms for the degradation and/or the detoxification of hazardous organic compounds is gaining wide acceptance as an alternative waste treatment technology. This work describes the unique capabilities of an isolated strain of Pseudomonas for metabolizing methylated aromatic compounds. This strain of Pseudomonas putida Idaho is unique in that it can tolerate and grow under a layer of neat p-xylene. A bioprocess has been developed to degrade LLW and mixed wastes containing methylated aromatic compounds, i.e., pseudocumene, toluene and p-xylene. The process is now in the demonstration phase at a DOE facility and has been running for one year. Feed concentrations of 21200 ppm of the toxic organic substrate have been fed to the bioreactor. This report describes the results obtained thus far

Cleaner bioprocesses for promoting zero-emission biofuels production in Vojvodina

Energy Technology Data Exchange (ETDEWEB)

Dodic, Sinisa N.; Vucurovic, Damjan G.; Popov, Stevan D.; Dodic, Jelena M.; Rankovic, Jovana A. [Department of Biotechnology and Pharmaceutical Engineering, Faculty of Technology, University of Novi Sad, Bul. cara Lazara 1, Novi Sad 21000, Vojvodina (RS)

2010-12-15

In this study, the policy, market conditions and food security of biomass energy sources are assessed for supplying the future needs of Vojvodina. The Autonomous Province of Vojvodina is an autonomous province in Serbia, containing about 27% of its total population according to the 2002 Census. It is located in the northern part of the country, in the Pannonia plain, in southeastern Europe. Vojvodina is an energy-deficient province. The incentives to invest human and financial resources in the research and development of cleaner bioprocesses are high, considering the benefits which might be achieved in terms of environment protection and manufacturing costs. In the near and medium tenu, the development of bioprocesses for waste recycling and resource recovery might be one of the most viable options, considering much research work has already been done. In Vojvodina, there are technological solutions that biofuels produced in a closed cycle, so that the quantity of waste reduced to a minimum. These solutions include the stillage (remainder after distillation) used for fattening cattle, and cattle excrement to produce biogas and manure as fertilizer. The energy required for the production of bioethanol is obtained combustion lignocelullose residual waste from the production of basic raw materials starch, or biogas. Ash from the burned biomass returned to soil as a source of minerals for plants and replacement of mineral fertilizer. Such a closed cycle is economical for small farms in Vojvodina. (author)

Cleaner bioprocesses for promoting zero-emission biofuels production in Vojvodina

International Nuclear Information System (INIS)

Dodic, Sinisa N.; Vucurovic, Damjan G.; Popov, Stevan D.; Dodic, Jelena M.; Rankovic, Jovana A.

2010-01-01

In this study, the policy, market conditions and food security of biomass energy sources are assessed for supplying the future needs of Vojvodina. The Autonomous Province of Vojvodina is an autonomous province in Serbia, containing about 27% of its total population according to the 2002 Census. It is located in the northern part of the country, in the Pannonia plain, in southeastern Europe. Vojvodina is an energy-deficient province. The incentives to invest human and financial resources in the research and development of cleaner bioprocesses are high, considering the benefits which might be achieved in terms of environment protection and manufacturing costs. In the near and medium tenu, the development of bioprocesses for waste recycling and resource recovery might be one of the most viable options, considering much research work has already been done. In Vojvodina, there are technological solutions that biofuels produced in a closed cycle, so that the quantity of waste reduced to a minimum. These solutions include the stillage (remainder after distillation) used for fattening cattle, and cattle excrement to produce biogas and manure as fertilizer. The energy required for the production of bioethanol is obtained combustion lignocelullose residual waste from the production of basic raw materials starch, or biogas. Ash from the burned biomass returned to soil as a source of minerals for plants and replacement of mineral fertilizer. Such a closed cycle is economical for small farms in Vojvodina. (author)

The generic article

NARCIS (Netherlands)

Farkas, D.F.; Swart, Henriëtte de

2005-01-01

We take a fresh look at the connection between genericity and (in)definiteness by reconsidering a long-standing puzzle concerning the relation between definiteness and genericity. We contrast English on the one hand and Romance languages and Hungarian on the other, focusing on generic sentences

Origins of Cell-to-Cell Bioprocessing Diversity and Implications of the Extracellular Environment Revealed at the Single-Cell Level.

Science.gov (United States)

Vasdekis, A E; Silverman, A M; Stephanopoulos, G

2015-12-14

Bioprocess limitations imposed by microbial cell-to-cell phenotypic diversity remain poorly understood. To address this, we investigated the origins of such culture diversity during lipid production and assessed the impact of the fermentation microenvironment. We measured the single-cell lipid production dynamics in a time-invariant microfluidic environment and discovered that production is not monotonic, but rather sporadic with time. To characterize this, we introduce bioprocessing noise and identify its epigenetic origins. We linked such intracellular production fluctuations with cell-to-cell productivity diversity in culture. This unmasked the phenotypic diversity amplification by the culture microenvironment, a critical parameter in strain engineering as well as metabolic disease treatment.

Turmeric Bioprocessed with Mycelia from the Shiitake Culinary-Medicinal Mushroom Lentinus edodes (Agaricomycetes) Protects Mice Against Salmonellosis.

Science.gov (United States)

Kim, Sung Phil; Lee, Sang Jong; Nam, Seok Hyun; Friedman, Mendel

2017-01-01

This study investigated the suppressive mechanisms of an extract from bioprocessed Lentinus edodes mycelial liquid culture supplemented with turmeric (bioprocessed Curcuma longa extract [BPCLE]) against murine salmonellosis. The BPLCE extract from the bioprocessed mycelia of the Salmonella Typhimurium into murine RAW 264.7 macrophage cells, elimination of intracellular bacteria, and elevation of inducible nitric oxide synthase expression. Dietary administration of BPCLE activated leukocytes from the mice infected with Salmonella through the intraperitoneal route. The enzyme-linked immunosorbent assay of the cytokines produced by splenocytes from infected mice showed significant increases in the levels of Th1 cytokines, including interleukin (IL)-1β, IL-2, IL-6, and IL-12. Histology showed that dietary administration of BPCLE protected against necrosis of the liver resulting from a sublethal dose of Salmonella. In addition, the treatment (1) extended the lifespan of lethally infected mice, (2) suppressed the invasion of Salmonella into human Caco-2 colorectal adenocarcinoma cells, (3) increased excretion of the bacterium in the feces, (4) suppressed the translocation of the Salmonella to internal organs, and (5) increased total immunoglobulin A in both serum and intestinal fluids. BPCLE protected the mice against salmonellosis via cooperative effects that include the upregulation of the Th1 immune reaction, prevention of translocation of bacteria across the intestinal epithelial cells, and increased immunoglobulin A production in serum and intestinal fluids.

A framework for model-based optimization of bioprocesses under uncertainty: Identifying critical parameters and operating variables

DEFF Research Database (Denmark)

Morales Rodriguez, Ricardo; Meyer, Anne S.; Gernaey, Krist

2011-01-01

This study presents the development and application of a systematic model-based framework for bioprocess optimization, evaluated on a cellulosic ethanol production case study. The implementation of the framework involves the use of dynamic simulations, sophisticated uncertainty analysis (Monte...

Bioprocessing strategies for the large-scale production of human mesenchymal stem cells: a review.

Science.gov (United States)

Panchalingam, Krishna M; Jung, Sunghoon; Rosenberg, Lawrence; Behie, Leo A

2015-11-23

Human mesenchymal stem cells (hMSCs), also called mesenchymal stromal cells, have been of great interest in regenerative medicine applications because of not only their differentiation potential but also their ability to secrete bioactive factors that can modulate the immune system and promote tissue repair. This potential has initiated many early-phase clinical studies for the treatment of various diseases, disorders, and injuries by using either hMSCs themselves or their secreted products. Currently, hMSCs for clinical use are generated through conventional static adherent cultures in the presence of fetal bovine serum or human-sourced supplements. However, these methods suffer from variable culture conditions (i.e., ill-defined medium components and heterogeneous culture environment) and thus are not ideal procedures to meet the expected future demand of quality-assured hMSCs for human therapeutic use. Optimizing a bioprocess to generate hMSCs or their secreted products (or both) promises to improve the efficacy as well as safety of this stem cell therapy. In this review, current media and methods for hMSC culture are outlined and bioprocess development strategies discussed.

Consolidated bioprocessing for butyric acid production from rice straw with undefined mixed culture

Directory of Open Access Journals (Sweden)

Binling Ai

2016-10-01

Full Text Available Lignocellulosic biomass is a renewable source with great potential for biofuels and bioproducts. However, the cost of cellulolytic enzymes limits the utilization of the low-cost bioresource. This study aimed to develop a consolidated bioprocessing without the need of supplementary cellulase for butyric acid production from lignocellulosic biomass. A stirred-tank reactor with a working volume of 21 L was constructed and operated in batch and semi-continuous fermentation modes with a cellulolytic butyrate-producing microbial community. The semi-continuous fermentation with intermittent discharging of the culture broth and replenishment with fresh medium achieved the highest butyric acid productivity of 2.69 g/(L•d. In semi-continuous operation mode, the butyric acid and total carboxylic acid concentrations of 16.2 and 28.9 g/L, respectively, were achieved. Over the 21-day fermentation period, their cumulative yields reached 1189 and 2048 g, respectively, corresponding to 41% and 74% of the maximum theoretical yields based on the amount of NaOH pretreated rice straw fed in. This study demonstrated that an undefined mixed culture-based consolidated bioprocessing for butyric acid production can completely eliminate the cost of supplementary cellulolytic enzymes.

Consolidated Bioprocessing for Butyric Acid Production from Rice Straw with Undefined Mixed Culture.

Science.gov (United States)

Ai, Binling; Chi, Xue; Meng, Jia; Sheng, Zhanwu; Zheng, Lili; Zheng, Xiaoyan; Li, Jianzheng

2016-01-01

Lignocellulosic biomass is a renewable source with great potential for biofuels and bioproducts. However, the cost of cellulolytic enzymes limits the utilization of the low-cost bioresource. This study aimed to develop a consolidated bioprocessing without the need of supplementary cellulase for butyric acid production from lignocellulosic biomass. A stirred-tank reactor with a working volume of 21 L was constructed and operated in batch and semi-continuous fermentation modes with a cellulolytic butyrate-producing microbial community. The semi-continuous fermentation with intermittent discharging of the culture broth and replenishment with fresh medium achieved the highest butyric acid productivity of 2.69 g/(L· d). In semi-continuous operation mode, the butyric acid and total carboxylic acid concentrations of 16.2 and 28.9 g/L, respectively, were achieved. Over the 21-day fermentation period, their cumulative yields reached 1189 and 2048 g, respectively, corresponding to 41 and 74% of the maximum theoretical yields based on the amount of NaOH pretreated rice straw fed in. This study demonstrated that an undefined mixed culture-based consolidated bioprocessing for butyric acid production can completely eliminate the cost of supplementary cellulolytic enzymes.

[Generic drugs: good or bad? Physician's knowledge of generic drugs and prescribing habits].

Science.gov (United States)

García, A J; Martos, F; Leiva, F; Sánchez de la Cuesta, F

2003-01-01

In this article we analyze the responses of 1220 Spanish physicians who participated in a survery about generic drugs. A previously validated questionnaire was sent to physicians through the Spanish Medical Councils of the different provinces. Four items were analyzed: what doctors know about generic drugs (knowledge); physicians' prescribing habits concerning these drugs (attitude and professional competence); how prescription of generic drugs effects pharmaceutical costs amd, finally, what doctors believe a generic drug should be. The influence of physician-related variables (age, type of contract, specialty, workload, etc.) on prescribing of generic drugs was also analyzed. In view of the results, we believe that to rationalize expenditure through and appropriate policy on generic drugs Spanish health authorities should offer more and better training and information (clear and independent) about what generic drugs are.

Application of Raman Spectroscopy and Univariate Modelling As a Process Analytical Technology for Cell Therapy Bioprocessing

Science.gov (United States)

Baradez, Marc-Olivier; Biziato, Daniela; Hassan, Enas; Marshall, Damian

2018-01-01

Cell therapies offer unquestionable promises for the treatment, and in some cases even the cure, of complex diseases. As we start to see more of these therapies gaining market authorization, attention is turning to the bioprocesses used for their manufacture, in particular the challenge of gaining higher levels of process control to help regulate cell behavior, manage process variability, and deliver product of a consistent quality. Many processes already incorporate the measurement of key markers such as nutrient consumption, metabolite production, and cell concentration, but these are often performed off-line and only at set time points in the process. Having the ability to monitor these markers in real-time using in-line sensors would offer significant advantages, allowing faster decision-making and a finer level of process control. In this study, we use Raman spectroscopy as an in-line optical sensor for bioprocess monitoring of an autologous T-cell immunotherapy model produced in a stirred tank bioreactor system. Using reference datasets generated on a standard bioanalyzer, we develop chemometric models from the Raman spectra for glucose, glutamine, lactate, and ammonia. These chemometric models can accurately monitor donor-specific increases in nutrient consumption and metabolite production as the primary T-cell transition from a recovery phase and begin proliferating. Using a univariate modeling approach, we then show how changes in peak intensity within the Raman spectra can be correlated with cell concentration and viability. These models, which act as surrogate markers, can be used to monitor cell behavior including cell proliferation rates, proliferative capacity, and transition of the cells to a quiescent phenotype. Finally, using the univariate models, we also demonstrate how Raman spectroscopy can be applied for real-time monitoring. The ability to measure these key parameters using an in-line Raman optical sensor makes it possible to have immediate

Application of Raman Spectroscopy and Univariate Modelling As a Process Analytical Technology for Cell Therapy Bioprocessing.

Science.gov (United States)

Baradez, Marc-Olivier; Biziato, Daniela; Hassan, Enas; Marshall, Damian

2018-01-01

Cell therapies offer unquestionable promises for the treatment, and in some cases even the cure, of complex diseases. As we start to see more of these therapies gaining market authorization, attention is turning to the bioprocesses used for their manufacture, in particular the challenge of gaining higher levels of process control to help regulate cell behavior, manage process variability, and deliver product of a consistent quality. Many processes already incorporate the measurement of key markers such as nutrient consumption, metabolite production, and cell concentration, but these are often performed off-line and only at set time points in the process. Having the ability to monitor these markers in real-time using in-line sensors would offer significant advantages, allowing faster decision-making and a finer level of process control. In this study, we use Raman spectroscopy as an in-line optical sensor for bioprocess monitoring of an autologous T-cell immunotherapy model produced in a stirred tank bioreactor system. Using reference datasets generated on a standard bioanalyzer, we develop chemometric models from the Raman spectra for glucose, glutamine, lactate, and ammonia. These chemometric models can accurately monitor donor-specific increases in nutrient consumption and metabolite production as the primary T-cell transition from a recovery phase and begin proliferating. Using a univariate modeling approach, we then show how changes in peak intensity within the Raman spectra can be correlated with cell concentration and viability. These models, which act as surrogate markers, can be used to monitor cell behavior including cell proliferation rates, proliferative capacity, and transition of the cells to a quiescent phenotype. Finally, using the univariate models, we also demonstrate how Raman spectroscopy can be applied for real-time monitoring. The ability to measure these key parameters using an in-line Raman optical sensor makes it possible to have immediate

Application of Raman Spectroscopy and Univariate Modelling As a Process Analytical Technology for Cell Therapy Bioprocessing

Directory of Open Access Journals (Sweden)

Marc-Olivier Baradez

2018-03-01

Full Text Available Cell therapies offer unquestionable promises for the treatment, and in some cases even the cure, of complex diseases. As we start to see more of these therapies gaining market authorization, attention is turning to the bioprocesses used for their manufacture, in particular the challenge of gaining higher levels of process control to help regulate cell behavior, manage process variability, and deliver product of a consistent quality. Many processes already incorporate the measurement of key markers such as nutrient consumption, metabolite production, and cell concentration, but these are often performed off-line and only at set time points in the process. Having the ability to monitor these markers in real-time using in-line sensors would offer significant advantages, allowing faster decision-making and a finer level of process control. In this study, we use Raman spectroscopy as an in-line optical sensor for bioprocess monitoring of an autologous T-cell immunotherapy model produced in a stirred tank bioreactor system. Using reference datasets generated on a standard bioanalyzer, we develop chemometric models from the Raman spectra for glucose, glutamine, lactate, and ammonia. These chemometric models can accurately monitor donor-specific increases in nutrient consumption and metabolite production as the primary T-cell transition from a recovery phase and begin proliferating. Using a univariate modeling approach, we then show how changes in peak intensity within the Raman spectra can be correlated with cell concentration and viability. These models, which act as surrogate markers, can be used to monitor cell behavior including cell proliferation rates, proliferative capacity, and transition of the cells to a quiescent phenotype. Finally, using the univariate models, we also demonstrate how Raman spectroscopy can be applied for real-time monitoring. The ability to measure these key parameters using an in-line Raman optical sensor makes it possible

Commercial-grade motors in safety-related applications: Final report

International Nuclear Information System (INIS)

Holzman, P.M.

1988-04-01

The objective of this project was to discuss the process necessary to utilize commercial grade equipment in safety related applications and to provide utilities with guidance for accepting commercial grade motors for safety-related applications. The generic commercial-grade concepts presented in this report can be successfully applied to motors. Commercial grade item utilization has the greatest applicability to motors in ''mild'' environments, because these motors are essentially similar to commercial grade motors in materials, construction methods, and capabilities. The acceptance process is less applicable to motors that are subject to ''harsh'' environments during postulated accidents, because of the unique design features and testing required to qualify these motors

Production of polyol oils from soybean oil by bioprocess and Philippines edible medicinal wild mushrooms

Science.gov (United States)

We have been trying to develop a bioprocess for the production of polyol oils directly from soybean oil. We reported earlier the polyol products produced from soybean oil by Acinetobacter haemolyticus A01-35 (NRRL B-59985) (Hou and Lin, 2013). The objective of this study is to identify the chemical ...

Trends in Process Analytical Technology: Present State in Bioprocessing.

Science.gov (United States)

Jenzsch, Marco; Bell, Christian; Buziol, Stefan; Kepert, Felix; Wegele, Harald; Hakemeyer, Christian

2017-08-04

Process analytical technology (PAT), the regulatory initiative for incorporating quality in pharmaceutical manufacturing, is an area of intense research and interest. If PAT is effectively applied to bioprocesses, this can increase process understanding and control, and mitigate the risk from substandard drug products to both manufacturer and patient. To optimize the benefits of PAT, the entire PAT framework must be considered and each elements of PAT must be carefully selected, including sensor and analytical technology, data analysis techniques, control strategies and algorithms, and process optimization routines. This chapter discusses the current state of PAT in the biopharmaceutical industry, including several case studies demonstrating the degree of maturity of various PAT tools. Graphical Abstract Hierarchy of QbD components.

The Solubility of Cr-Organic Produced by Hydrolysis, Bioprocess and Bioremediation and its Effect on Fermented Rate, Digestibility and Rumen Microbe Population (in vitro

Directory of Open Access Journals (Sweden)

UH Tanuwiria

2010-09-01

Full Text Available The research was conducted to study the production of organic chromium from the leather tanning waste and its effect on in vitro rumen fermentation activities. The research was divided into two phases. The first phase was production of organic chromium by alkali hydrolysis, S cereviceae bioprocess, and duckweed bioremediation that perceived solubility in neutral and acid solution. The second phase was the supplementation of organic-Cr in ration seen from in-vitro fermented rate, digestibility and microbe rumen population. Research was conducted experimentally using 4x4 factorial patterns, on the basis of Completely Randomized Design (CRD with three replications in each experimental unit. The first factor was the type of organic-Cr and the second factor was the supplement in ration at four levels, 1, 2, 3 and 4 ppm. The results of this research indicated that organic chromium can be synthesized by alkali hydrolysis, S cereviseae bioprocess and the activity of duckweed bioremediation. Among the three of processes referred, the highest level of Cr was obtained from S cereviseae bioprocess that was originated from leather-tanning waste. The levels of organic-Cr that was resulted from alkali hydrolysis, bioprocess from Cl3Cr.6H2O, bioprocess from Cr leather-tanning waste, and from duckweed bioremediation were 354, 1011, 3833 and 310 mg/kg, respectively. Organic-Cr characteristic of each product has relatively similar in ferment ability, dry matter and organic matter digestibility and rumen ecosystem. There is an indication that dry matter and organic matter digestibility and rumen microbe population in ration that was added with organic Cr from alkali hydrolysis was higher than other supplements. (Animal Production 12(3: 175-183 (2010Key Words: organic-Cr, rumen fermentation activities, rumen microbe population

Brand vs generic adverse event reporting patterns: An authorized generic-controlled evaluation of cardiovascular medications.

Science.gov (United States)

Alatawi, Y; Rahman, Md M; Cheng, N; Qian, J; Peissig, P L; Berg, R L; Page, C D; Hansen, R A

2018-06-01

Some public scepticism exists about generics in terms of whether brand and generic drugs produce identical outcomes. This study explores whether adverse event (AE) reporting patterns are similar between brand and generic drugs, using authorized generics (AGs) as a control for possible generic drug perception biases. Events reported to the FDA Adverse Event Reporting System from the years 2004-2015 were analysed. Drugs were classified as brand, AG or generic based on drug and manufacturer names. Reports were included if amlodipine, losartan, metoprolol extended release (ER) or simvastatin were listed as primary or secondary suspect drugs. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting labelled AEs compared to reporting these AEs with all other drugs. The Breslow-Day test compared RORs across brand, AG and generic. Interrupted time series analysis evaluated the impact of generic entry on reporting trends. Generics accounted for significant percentages of total U.S. reports, but AGs accounted for smaller percentages of reports, including for amlodipine (14.26%), losartan (1.48%), metoprolol ER (0.35%) and simvastatin (0.70%). Whereas the RORs were significantly different for multiple brand vs generic comparisons, the AG vs generic comparisons yielded fewer statistically significant findings. Namely, only the ROR for AG differed from generic for amlodipine with peripheral oedema (P brand and generic compared with AG and generic. Use of AGs as a control for perception biases against generics is useful, but this approach can be limited by small AG report numbers. Requiring the manufacturer name to be printed on the prescription bottle or packaging could improve the accuracy of assignment for products being reported. © 2017 John Wiley & Sons Ltd.

Upgrading protein products using bioprocessing on agricultural crops

DEFF Research Database (Denmark)

Sulewska, Anna Maria; Sørensen, Jens Christian; Markedal, Keld Ejdrup

to sustainability leads to a demand for plant protein products made from locally grown crops. Novel bioprocessing methods have been developed to generate protein products which are nutritious, readily available and do not generate hazardous waste. The processing focus has therefore been on developing protein......Due to increasing world population, higher average income, and changes in food preferences, there is a growing demand for proteins, especially novel plant-based protein sources, that can substitute animal proteins and supplement currently used soya proteins. Increased customer awareness......-enriched products with minimized content of antinutritional compounds. For every crop it is a challenge to obtain protein fractions with sufficient added value to make processing economically feasible. In this work we present the characterization of protein products developed in pilot scale using the novel...

Savannah River Site generic data base development

International Nuclear Information System (INIS)

Blanchard, A.

2000-01-01

This report describes the results of a project to improve the generic component failure database for the Savannah River Site (SRS). Additionally, guidelines were developed further for more advanced applications of database values. A representative list of components and failure modes for SRS risk models was generated by reviewing existing safety analyses and component failure data bases and from suggestions from SRS safety analysts. Then sources of data or failure rate estimates were identified and reviewed for applicability. A major source of information was the Nuclear Computerized Library for Assessing Reactor Reliability, or NUCLARR. This source includes an extensive collection of failure data and failure rate estimates for commercial nuclear power plants. A recent Idaho National Engineering Laboratory report on failure data from the Idaho Chemical Processing Plant was also reviewed. From these and other recent sources, failure data and failure rate estimates were collected for the components and failure modes of interest. For each component failure mode, this information was aggregated to obtain a recommended generic failure rate distribution (mean and error factor based on a lognormal distribution). Results are presented in a table in this report. A major difference between generic database and previous efforts is that this effort estimates failure rates based on actual data (failure events) rather than on existing failure rate estimates. This effort was successful in that over 75% of the results are now based on actual data. Also included is a section on guidelines for more advanced applications of failure rate data. This report describes the results of a project to improve the generic component failure database for the Savannah River site (SRS). Additionally, guidelines were developed further for more advanced applications of database values

Turmeric bioprocessed with mycelia from the shiitake culinary-medicinal mushroom lentinus edodes (agaricomycetes) protects mice against salmonellosis

Science.gov (United States)

Extracts of the shiitake mushroom Lentinus edodes and the spice tumeric (Curcuma longa) have both been reported to have health-promoting properties. The present study investigated the suppressive mechanisms of a bioprocessed Lentinus edodes liquid mushroom mycelia culture supplemented with turmeric ...

Studies on generalized kinetic model and Pareto optimization of a product-driven self-cycling bioprocess.

Science.gov (United States)

Sun, Kaibiao; Kasperski, Andrzej; Tian, Yuan

2014-10-01

The aim of this study is the optimization of a product-driven self-cycling bioprocess and presentation of a way to determine the best possible decision variables out of a set of alternatives based on the designed model. Initially, a product-driven generalized kinetic model, which allows a flexible choice of the most appropriate kinetics is designed and analysed. The optimization problem is given as the bi-objective one, where maximization of biomass productivity and minimization of unproductive loss of substrate are the objective functions. Then, the Pareto fronts are calculated for exemplary kinetics. It is found that in the designed bioprocess, a decrease of emptying/refilling fraction and an increase of substrate feeding concentration cause an increase of the biomass productivity. An increase of emptying/refilling fraction and a decrease of substrate feeding concentration cause a decrease of unproductive loss of substrate. The preferred solutions are calculated using the minimum distance from an ideal solution method, while giving proposals of their modifications derived from a decision maker's reactions to the generated solutions.

Generic antibiotics in Japan.

Science.gov (United States)

Fujimura, Shigeru; Watanabe, Akira

2012-08-01

Generic drugs have been used extensively in many developed countries, although their use in Japan has been limited. Generic drugs reduce drug expenses and thereby national medical expenditure. Because generic drugs provide advantages for both public administration and consumers, it is expected that they will be more widely used in the future. However, the diffusion rate of generic drugs in Japan is quite low compared with that of other developed countries. An investigation on generic drugs conducted by the Ministry of Health, Labour and Welfare in Japan revealed that 17.2 % of doctors and 37.2 % of patients had not used generic drugs. The major reasons for this low use rate included distrust of off-patent products and lower drug price margin compared with the brand name drug. The generic drugs available in the market include external drugs such as wet packs, antihypertensive agents, analgesics, anticancer drugs, and antibiotics. Among them, antibiotics are frequently used in cases of acute infectious diseases. When the treatment of these infections is delayed, the infection might be aggravated rapidly. The pharmacokinetics-pharmacodynamics (PK-PD) theory has been adopted in recent chemotherapy, and in many cases, the most appropriate dosage and administration of antibiotics are determined for individual patients considering renal function; high-dosage antibiotics are used preferably for a short duration. Therefore, a highly detailed antimicrobial agent is necessary. However, some of the generic antibiotics have less antibacterial potency or solubility than the brand name products. We showed that the potency of the generic products of vancomycin and teicoplanin is lower than that of the branded drugs by 14.6 % and 17.3 %, respectively. Furthermore, we confirmed that a generic meropenem drug for injection required about 82 s to solubilize in saline, whereas the brand product required only about 21 s. It was thought that the cause may be the difference in size of bulk

Technical Aspects of Use of Ultrasound for Intensification of Enzymatic Bio-Processing: New Path to "Green Chemistry"

Science.gov (United States)

Use of enzymatic processing in the food, textile, and bio-fuel applications is becoming increasingly popular, primarily because of rapid introduction of a new variety of highly efficient enzymes. In general, an enzymatic bio-processing generates less toxic and readily biodegradable wastewater efflue...

Nano-tubular cellulose for bioprocess technology development.

Science.gov (United States)

Koutinas, Athanasios A; Sypsas, Vasilios; Kandylis, Panagiotis; Michelis, Andreas; Bekatorou, Argyro; Kourkoutas, Yiannis; Kordulis, Christos; Lycourghiotis, Alexis; Banat, Ibrahim M; Nigam, Poonam; Marchant, Roger; Giannouli, Myrsini; Yianoulis, Panagiotis

2012-01-01

Delignified cellulosic material has shown a significant promotional effect on the alcoholic fermentation as yeast immobilization support. However, its potential for further biotechnological development is unexploited. This study reports the characterization of this tubular/porous cellulosic material, which was done by SEM, porosimetry and X-ray powder diffractometry. The results showed that the structure of nano-tubular cellulose (NC) justifies its suitability for use in "cold pasteurization" processes and its promoting activity in bioprocessing (fermentation). The last was explained by a glucose pump theory. Also, it was demonstrated that crystallization of viscous invert sugar solutions during freeze drying could not be otherwise achieved unless NC was present. This effect as well as the feasibility of extremely low temperature fermentation are due to reduction of the activation energy, and have facilitated the development of technologies such as wine fermentations at home scale (in a domestic refrigerator). Moreover, NC may lead to new perspectives in research such as the development of new composites, templates for cylindrical nano-particles, etc.

Comparative analysis of solid-state bioprocessing and enzymatic treatment of finger millet for mobilization of bound phenolics.

Science.gov (United States)

Yadav, Geetanjali; Singh, Anshu; Bhattacharya, Patrali; Yuvraj, Jude; Banerjee, Rintu

2013-11-01

The present work investigates the probable bioprocessing technique to mobilize the bound phenolics naturally found in finger millet cell wall for enriching it with dietary antioxidants. Comparative study was performed between the exogenous enzymatic treatment and solid-state fermentation of grain (SSF) with a food grade organism Rhizopus oryzae. SSF results indicated that at the 6th day of incubation, total phenolic content (18.64 mg gallic acid equivalent/gds) and antioxidant property (DPPH radical scavenging activity of 39.03 %, metal chelating ability of 54 % and better reducing power) of finger millet were drastically enhanced when fermented with GRAS filamentous fungi. During the enzymatic bioprocessing, most of the phenolics released during the hydrolysis, leached out into the liquid portion rather than retaining them within the millet grain, resulting in overall loss of dietary antioxidant. The present study establishes the most effective strategy to enrich the finger millet with phenolic antioxidants.

An industrial perspective on bioreactor scale-down: what we can learn from combined large-scale bioprocess and model fluid studies.

Science.gov (United States)

Noorman, Henk

2011-08-01

For industrial bioreactor design, operation, control and optimization, the scale-down approach is often advocated to efficiently generate data on a small scale, and effectively apply suggested improvements to the industrial scale. In all cases it is important to ensure that the scale-down conditions are representative of the real large-scale bioprocess. Progress is hampered by limited detailed and local information from large-scale bioprocesses. Complementary to real fermentation studies, physical aspects of model fluids such as air-water in large bioreactors provide useful information with limited effort and cost. Still, in industrial practice, investments of time, capital and resources often prohibit systematic work, although, in the end, savings obtained in this way are trivial compared to the expenses that result from real process disturbances, batch failures, and non-flyers with loss of business opportunity. Here we try to highlight what can be learned from real large-scale bioprocess in combination with model fluid studies, and to provide suitable computation tools to overcome data restrictions. Focus is on a specific well-documented case for a 30-m(3) bioreactor. Areas for further research from an industrial perspective are also indicated. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Scripting XML with Generic Haskell

NARCIS (Netherlands)

Atanassow, F.; Clarke, D.; Jeuring, J.T.

2003-01-01

A generic program is written once and works on values of many data types. Generic Haskell is a recent extension of the functional programming language Haskell that supports generic programming. This paper discusses how Generic Haskell can be used to implement XML tools whose behaviour depends on

Scripting XML with Generic Haskell

NARCIS (Netherlands)

Atanassow, F.; Clarke, D.; Jeuring, J.T.

2007-01-01

A generic program is written once and works on values of many data types. Generic Haskell is a recent extension of the functional programming language Haskell that supports generic programming. This paper discusses how Generic Haskell can be used to implement XML tools whose behaviour depends on

High Generic Drug Prices and Market Competition: A Retrospective Cohort Study.

Science.gov (United States)

Dave, Chintan V; Kesselheim, Aaron S; Fox, Erin R; Qiu, Peihua; Hartzema, Abraham

2017-08-01

Prices for some generic drugs have increased in recent years, adversely affecting patients who rely on them. To determine the association between market competition levels and the change in generic drug prices in the United States. Retrospective cohort study. Prescription claims from commercial health plans between 2008 and 2013. The 5.5 years of data were divided into 11 study periods of 6 months each. The Herfindahl-Hirschman Index (HHI)-calculated by summing the squares of individual manufacturers' market shares, with higher values indicating a less competitive market-and average drug prices were estimated for the generic drugs in each period. The HHI value estimated in the baseline period (first half of 2008) was modeled as a fixed covariate. Models estimated price changes over time by level of competition, adjusting for drug shortages, market size, and dosage forms. From 1.08 billion prescription claims, a cohort of 1120 generic drugs was identified. After adjustment, drugs with quadropoly (HHI value of 2500, indicating relatively high levels of competition), duopoly (HHI value of 5000), near-monopoly (HHI value of 8000), and monopoly (HHI value of 10 000) levels of baseline competition were associated with price changes of -31.7% (95% CI, -34.4% to -28.9%), -11.8% (CI, -18.6% to -4.4%), 20.1% (CI, 5.5% to 36.6%), and 47.4% (CI, 25.4% to 73.2%), respectively, over the study period. Study findings may not be generalizable to drugs that became generic after 2008. Market competition levels were associated with a change in generic drug prices. Such measurements may be helpful in identifying older prescription drugs at higher risk for price change in the future. None.

Intelligent control of mixed-culture bioprocesses

International Nuclear Information System (INIS)

Stoner, D.L.; Larsen, E.D.; Miller, K.S.

1995-01-01

A hierarchical control system is being developed and applied to a mixed culture bioprocess in a continuous stirred tank reactor. A bioreactor, with its inherent complexity and non-linear behavior was an interesting, yet, difficult application for control theory. The bottom level of the hierarchy was implemented as a number of integrated set point controls and data acquisition modules. Within the second level was a diagnostic system that used expert knowledge to determine the operational status of the sensors, actuators, and control modules. A diagnostic program was successfully implemented for the detection of stirrer malfunctions, and to monitor liquid delivery rates and recalibrate the pumps when deviations from desired flow rates occurred. The highest control level was a supervisory shell that was developed using expert knowledge and the history of the reactor operation to determine the set points required to meet a set of production criteria. At this stage the supervisory shell analyzed the data to determine the state of the system. In future implementations, this shell will determine the set points required to optimize a cost function using expert knowledge and adaptive learning techniques

Intelligent control of mixed-culture bioprocesses

Energy Technology Data Exchange (ETDEWEB)

Stoner, D.L.; Larsen, E.D.; Miller, K.S. [Idaho National Engineering Lab., Idaho Falls, ID (United States)] [and others

1995-12-31

A hierarchical control system is being developed and applied to a mixed culture bioprocess in a continuous stirred tank reactor. A bioreactor, with its inherent complexity and non-linear behavior was an interesting, yet, difficult application for control theory. The bottom level of the hierarchy was implemented as a number of integrated set point controls and data acquisition modules. Within the second level was a diagnostic system that used expert knowledge to determine the operational status of the sensors, actuators, and control modules. A diagnostic program was successfully implemented for the detection of stirrer malfunctions, and to monitor liquid delivery rates and recalibrate the pumps when deviations from desired flow rates occurred. The highest control level was a supervisory shell that was developed using expert knowledge and the history of the reactor operation to determine the set points required to meet a set of production criteria. At this stage the supervisory shell analyzed the data to determine the state of the system. In future implementations, this shell will determine the set points required to optimize a cost function using expert knowledge and adaptive learning techniques.

77 FR 66744 - Temporary Rule to Increase the Commercial Annual Catch Limit for South Atlantic Yellowtail Snapper

Science.gov (United States)

2012-11-07

... South Atlantic Comprehensive ACL Amendment and the Generic ACL Amendment to the Red Drum, Reef Fish Resources, Shrimp, and Coral and Coral Reefs FMPs for the Gulf of Mexico (Generic ACL Amendment) (76 FR... (518,270 kg), round weight. The AM implemented through that rule states that the commercial sector will...

In vitro disintegration studies of weekly generic and branded risedronate sodium formulations available in Canada.

Science.gov (United States)

Walker, A D; Adachi, J D

2011-09-01

The aim of this study was to evaluate the in vitro disintegration of the five newly available Canadian generic risedronate 35 mg tablets compared to the innovator (branded) product, ACTONEL * *ACTONEL is a registered trade name of Warner Chilcott Company, LLC. (risedronate sodium) 35 mg. Tablets were inspected for colour and appearance. Disintegration times were determined using United States Pharmacopeia 33 (USP33-NF 28) methods. Disintegration onset time was also evaluated. The mean disintegration onset time values for the generic risedronate 35 mg tablets ranged from 2 to 29 seconds, and the mean disintegration completion times ranged from 81 to 260 seconds. The mean disintegration onset and completion time values for the ACTONEL 35 mg tablets were 23 and 43 seconds respectively. Four out of the five generic tablets tested had shorter disintegration onset times than the branded product; two of the generic tablet products had very fast disintegration onset times i.e. 2-3 seconds. Disintegration completion time for all five generic products tested was longer than that observed for the branded product; two generic products had disintegration completion time values five to six times longer than the branded product. Differences in the in vitro disintegration times were observed between the generic risedronate 35 mg tablets commercially available in Canada and the branded product, ACTONEL. The rapid disintegration onset times of two generic products may be important as this could increase the possibility of drug exposure in both the mouth and the esophagus during swallowing, resulting in unwanted localized irritation. However, it should be noted that an in vitro/in vivo correlation has not been established. Until such studies are completed it may be important to be aware of such in vitro disintegration differences when evaluating patients with newly presenting upper gastrointestinal complaints upon being switched from the branded product to generic formulations.

From university research to commercial product (Conference Presentation)

Science.gov (United States)

Mathuis, Philip

2016-03-01

Ovizio Imaging Systems, a quantitative microscopic imaging spin-off of the Université Libre de Bruxelles, Belgium, was founded in the beginning of 2010 by Philip Mathuis, Serge Jooris, Prof. Frank Dubois and Dr. Catherine Yourassowky. The company has launched a range of specialized microscopy instruments for quantitative imaging mainly focused on the bioprocessing and diagnostics fields within the life sciences market. During my talk I will present the story of how an idea, emerged from the research labs of the University made it to a manufactured and sold product. The talk will look at many aspects of entrepreneurship and setting up a company, finding the funding for the project, attracting people, industrialization and product design and commercialization. It will also be focused on choices one has to make during the start-up phase and methodologies that can be applied in many different settings.

Optimizing Generic Functions

NARCIS (Netherlands)

Alimarine, A.; Smetsers, J.E.W.

2004-01-01

Generic functions are defined by induction on the structural representation of types. As a consequence, by defining just a single generic operation, one acquires this operation over any particular type. An instance on a specific type is generated by interpretation of the type's structure. A direct

Nano-tubular cellulose for bioprocess technology development.

Directory of Open Access Journals (Sweden)

Athanasios A Koutinas

Full Text Available Delignified cellulosic material has shown a significant promotional effect on the alcoholic fermentation as yeast immobilization support. However, its potential for further biotechnological development is unexploited. This study reports the characterization of this tubular/porous cellulosic material, which was done by SEM, porosimetry and X-ray powder diffractometry. The results showed that the structure of nano-tubular cellulose (NC justifies its suitability for use in "cold pasteurization" processes and its promoting activity in bioprocessing (fermentation. The last was explained by a glucose pump theory. Also, it was demonstrated that crystallization of viscous invert sugar solutions during freeze drying could not be otherwise achieved unless NC was present. This effect as well as the feasibility of extremely low temperature fermentation are due to reduction of the activation energy, and have facilitated the development of technologies such as wine fermentations at home scale (in a domestic refrigerator. Moreover, NC may lead to new perspectives in research such as the development of new composites, templates for cylindrical nano-particles, etc.

Selection of controlled variables in bioprocesses. Application to a SHARON-Anammox process for autotrophic nitrogen removal

DEFF Research Database (Denmark)

Mauricio Iglesias, Miguel; Valverde Perez, Borja; Sin, Gürkan

Selecting the right controlled variables in a bioprocess is challenging since the objectives of the process (yields, product or substrate concentration) are difficult to relate with a given actuator. We apply here process control tools that can be used to assist in the selection of controlled var...... variables to the case of the SHARON-Anammox process for autotrophic nitrogen removal....

Generic Example Proving Criteria for All

Science.gov (United States)

Yopp, David; Ely, Rob; Johnson­-Leung, Jennifer

2015-01-01

We review literature that discusses generic example proving and highlight ambiguities that pervade our research community's discourse about generic example arguments. We distinguish between pedagogical advice for choosing good examples that can serve as generic examples when teaching and advice for developing generic example arguments. We provide…

Generic and biosimilar medicines: quid?

Directory of Open Access Journals (Sweden)

Steven Simoens

2012-12-01

Full Text Available Once intellectual property protection, data and marketing exclusivity of reference medicines have expired, generic medicines and biosimilar medicines can enter the off-patent market. This market entry is conditional on the approval of marketing authorization, pricing and reimbursement. Given that there tends to be confusion surrounding generic and biosimilar medicines, this Editorial introduces basic concepts related to generic and biosimilar medicines and presents the different studies and articles included in this supplement dedicated to generic and biosimilar medicines.

Evaluation and proposed improvements to effectiveness of US Nuclear Regulatory Commission generic communications

International Nuclear Information System (INIS)

Thurber, J.A.; Melber, B.D.; Geisendorfer, C.L.; Vallario, R.W.

1988-01-01

This report describes an evaluation of NRC generic communications with industry concerning safety related issues of commercial nuclear power plandts. The analysis builds on the findings presented in the 1986 Office of Analysis and Evaluation of Operational Data (AEOD) Special Study Report, ''An Overview of Nuclear Power Plant Operating Experience Feedback Programs'' (AEOD/S602). The primary objective of the report is to present practical recommendations for improving NRC's documents and generic communications system. The report is based upon a systematic review and evaluation of NRC and industry operating experience documents. It also includes an analysis of interviews with licensee personnel at five utilities and their nuclear power plants. NRC regional and headquarters managers and staff were also interviewed for the study. NRC and licensee personnel interviewed are generally satisfied with the current NRC-industry communications system; however, several problems and potential solutions to those problems are identified in this study. The report makes seven major recommendations for improvement in the effectiveness of NRC-industry generic communications about nuclear power plant operating experience

Business-Level Strategy for the Foreign Commercial Banks operating within Malaysia

OpenAIRE

Rasool Khan, Mohamed Rizal

2007-01-01

This paper discusses the strategic positioning and use of Porter’s (1980) generic strategy framework within the foreign commercial banks operating in Malaysia. It was found that two distinct strategic groups were formed by the foreign commercial banks. Performance analysis conducted suggests that banks with clearer strategic direction managed to outperform its peers in its strategic group. Furthermore, the performance of one strategic group was significantly lower than that of the second.

Advertising and generic market entry.

Science.gov (United States)

Königbauer, Ingrid

2007-03-01

The effect of purely persuasive advertising on generic market entry and social welfare is analysed. An incumbent has the possibility to invest in advertising which affects the prescribing physician's perceived relative qualities of the brand-name and the generic version of the drug. Advertising creates product differentiation and can induce generic market entry which is deterred without differentiation due to strong Bertrand competition. However, over-investment in advertising can deter generic market entry under certain conditions and reduces welfare as compared to accommodated market entry.

Bio-processing of solid wastes and secondary resources for metal extraction – A review

International Nuclear Information System (INIS)

Lee, Jae-chun; Pandey, Banshi Dhar

2012-01-01

Highlights: ► Review focuses on bio-extraction of metals from solid wastes of industries and consumer goods. ► Bio-processing of certain effluents/wastewaters with metals is also included in brief. ► Quantity/composition of wastes are assessed, and microbes used and leaching conditions included. ► Bio-recovery using bacteria, fungi and archaea is highlighted for resource recycling. ► Process methodology/mechanism, R and D direction and scope of large scale use are briefly included. - Abstract: Metal containing wastes/byproducts of various industries, used consumer goods, and municipal waste are potential pollutants, if not treated properly. They may also be important secondary resources if processed in eco-friendly manner for secured supply of contained metals/materials. Bio-extraction of metals from such resources with microbes such as bacteria, fungi and archaea is being increasingly explored to meet the twin objectives of resource recycling and pollution mitigation. This review focuses on the bio-processing of solid wastes/byproducts of metallurgical and manufacturing industries, chemical/petrochemical plants, electroplating and tanning units, besides sewage sludge and fly ash of municipal incinerators, electronic wastes (e-wastes/PCBs), used batteries, etc. An assessment has been made to quantify the wastes generated and its compositions, microbes used, metal leaching efficiency etc. Processing of certain effluents and wastewaters comprising of metals is also included in brief. Future directions of research are highlighted.

Commercial grade item (CGI) dedication of generators for nuclear safety related applications

International Nuclear Information System (INIS)

Das, R.K.; Hajos, L.G.

1993-01-01

The number of nuclear safety related equipment suppliers and the availability of spare and replacement parts designed specifically for nuclear safety related application are shrinking rapidly. These have made it necessary for utilities to apply commercial grade spare and replacement parts in nuclear safety related applications after implementing proper acceptance and dedication process to verify that such items conform with the requirements of their use in nuclear safety related application. The general guidelines for the commercial grade item (CGI) acceptance and dedication are provided in US Nuclear Regulatory Commission (NRC) Generic Letters and Electric Power Research Institute (EPRI) Report NP-5652, Guideline for the Utilization of Commercial Grade Items in Nuclear Safety Related Applications. This paper presents an application of these generic guidelines for procurement, acceptance, and dedication of a commercial grade generator for use as a standby generator at Salem Generating Station Units 1 and 2. The paper identifies the critical characteristics of the generator which once verified, will provide reasonable assurance that the generator will perform its intended safety function. The paper also delineates the method of verification of the critical characteristics through tests and provide acceptance criteria for the test results. The methodology presented in this paper may be used as specific guidelines for reliable and cost effective procurement and dedication of commercial grade generators for use as standby generators at nuclear power plants

Mitigative techniques and analysis of generic site conditions for ground-water contamination associated with severe accidents

Energy Technology Data Exchange (ETDEWEB)

Shafer, J.M.; Oberlander, P.L.; Skaggs, R.L.

1984-04-01

The purpose of this study is to evaluate the feasibility of using ground-water contaminant mitigation techniques to control radionuclide migration following a severe commercial nuclear power reactor accident. The two types of severe commercial reactor accidents investigated are: (1) containment basemat penetration of core melt debris which slowly cools and leaches radionuclides to the subsurface environment, and (2) containment basemat penetration of sump water without full penetration of the core mass. Six generic hydrogeologic site classifications are developed from an evaluation of reported data pertaining to the hydrogeologic properties of all existing and proposed commercial reactor sites. One-dimensional radionuclide transport analyses are conducted on each of the individual reactor sites to determine the generic characteristics of a radionuclide discharge to an accessible environment. Ground-water contaminant mitigation techniques that may be suitable, depending on specific site and accident conditions, for severe power plant accidents are identified and evaluated. Feasible mitigative techniques and associated constraints on feasibility are determined for each of the six hydrogeologic site classifications. The first of three case studies is conducted on a site located on the Texas Gulf Coastal Plain. Mitigative strategies are evaluated for their impact on contaminant transport and results show that the techniques evaluated significantly increased ground-water travel times. 31 references, 118 figures, 62 tables.

Mitigative techniques and analysis of generic site conditions for ground-water contamination associated with severe accidents

International Nuclear Information System (INIS)

Shafer, J.M.; Oberlander, P.L.; Skaggs, R.L.

1984-04-01

The purpose of this study is to evaluate the feasibility of using ground-water contaminant mitigation techniques to control radionuclide migration following a severe commercial nuclear power reactor accident. The two types of severe commercial reactor accidents investigated are: (1) containment basemat penetration of core melt debris which slowly cools and leaches radionuclides to the subsurface environment, and (2) containment basemat penetration of sump water without full penetration of the core mass. Six generic hydrogeologic site classifications are developed from an evaluation of reported data pertaining to the hydrogeologic properties of all existing and proposed commercial reactor sites. One-dimensional radionuclide transport analyses are conducted on each of the individual reactor sites to determine the generic characteristics of a radionuclide discharge to an accessible environment. Ground-water contaminant mitigation techniques that may be suitable, depending on specific site and accident conditions, for severe power plant accidents are identified and evaluated. Feasible mitigative techniques and associated constraints on feasibility are determined for each of the six hydrogeologic site classifications. The first of three case studies is conducted on a site located on the Texas Gulf Coastal Plain. Mitigative strategies are evaluated for their impact on contaminant transport and results show that the techniques evaluated significantly increased ground-water travel times. 31 references, 118 figures, 62 tables

Encouraging generic use can yield significant savings.

Science.gov (United States)

Zimmerman, Christina

2012-11-01

Key findings. (1) Zero copayment for generic drugs is the greatest influencer of generic statin utilization. (2) Both higher copayments for generic drugs and lower copayments for competing brands are associated with a decreased probability of using generic statins. (3) Prior authorization and step therapy requirements for brand-name statins are associated with an increased use of generic drugs. (4) Greater use of generic statins should reduce costs for patients, plans, and Medicare.

Simultaneous saccharification of inulin and starch using commercial glucoamylase and the subsequent bioconversion to high titer sorbitol and gluconic acid.

Science.gov (United States)

An, Kehong; Hu, Fengxian; Bao, Jie

2013-12-01

A new bioprocess for production of sorbitol and gluconic acid from two low-cost feedstocks, inulin and cassava starch, using a commercially available enzyme was proposed in this study. The commercial glucoamylase GA-L NEW from Genencor was found to demonstrate a high inulinase activity for hydrolysis of inulin into fructose and glucose. The glucoamylase was used to replace the expensive and not commercially available inulinase enzyme for simultaneous saccharification of inulin and starch into high titer glucose and fructose hydrolysate. The glucose and fructose in the hydrolysate were converted into sorbitol and gluconic acid using immobilized whole cells of the recombinant Zymomonas mobilis strain. The high gluconic acid concentration of 193 g/L and sorbitol concentration of 180 g/L with the overall yield of 97.3 % were obtained in the batch operations. The present study provided a practical production method of sorbitol and gluconic acid from low cost feedstocks and enzymes.

76 FR 57767 - Proposed Generic Communication; Draft NRC Generic Letter 2011-XX: Seismic Risk Evaluations for...

Science.gov (United States)

2011-09-16

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0204] Proposed Generic Communication; Draft NRC Generic Letter 2011-XX: Seismic Risk Evaluations for Operating Reactors AGENCY: Nuclear Regulatory Commission... FR 54507), that requested public comment on Draft NRC Generic Letter 2011- XX: Seismic Risk...

Bioprocessing applications in the management of nuclear and chemical wastes

International Nuclear Information System (INIS)

Genung, R.K.

1988-01-01

The projected requirements for waste management and environmental restoration activities within the United States will probably cost tens of billions of dollars annually during the next two decades. Expenditures of this magnitude clearly have the potential to affect the international competitiveness of many US industries and the continued operation of many federal facilities. It is argued that the costs of implementing current technology will be too high unless the standards and schedules for compliance are relaxed. Since this is socially unacceptable, efforts to improve the efficiency of existing technologies and to develop new technologies should be pursued. A sizable research, development, and demonstration effort can be easily justified if the potential for reducing costs can be shown. Bioprocessing systems for the treatment of nuclear and chemically hazardous wastes offer such promise. 11 refs

Generics Pricing: The Greek Paradox.

Science.gov (United States)

Karafyllis, Ioannis; Variti, Lamprini

2017-01-01

This paper explains and develops a methodological framework to help evaluate the performance of generic pharmaceutical policies and the correct evaluation of generics sales. Until today erroneous recording of generics does not help proper pricing and their penetration in the Greek market. This classifies Greece on the outliners in every study or comparison that is referred on papers or studies.

NET 40 Generics Beginner's Guide

CERN Document Server

Mukherjee, Sudipta

2012-01-01

This is a concise, practical guide that will help you learn Generics in .NET, with lots of real world and fun-to-build examples and clear explanations. It is packed with screenshots to aid your understanding of the process. This book is aimed at beginners in Generics. It assumes some working knowledge of C# , but it isn't mandatory. The following would get the most use out of the book: Newbie C# developers struggling with Generics. Experienced C++ and Java Programmers who are migrating to C# and looking for an alternative to other generic frameworks like STL and JCF would find this book handy.

Fluorescence Spectroscopy and Chemometric Modeling for Bioprocess Monitoring

Directory of Open Access Journals (Sweden)

Saskia M. Faassen

2015-04-01

Full Text Available On-line sensors for the detection of crucial process parameters are desirable for the monitoring, control and automation of processes in the biotechnology, food and pharma industry. Fluorescence spectroscopy as a highly developed and non-invasive technique that enables the on-line measurements of substrate and product concentrations or the identification of characteristic process states. During a cultivation process significant changes occur in the fluorescence spectra. By means of chemometric modeling, prediction models can be calculated and applied for process supervision and control to provide increased quality and the productivity of bioprocesses. A range of applications for different microorganisms and analytes has been proposed during the last years. This contribution provides an overview of different analysis methods for the measured fluorescence spectra and the model-building chemometric methods used for various microbial cultivations. Most of these processes are observed using the BioView® Sensor, thanks to its robustness and insensitivity to adverse process conditions. Beyond that, the PLS-method is the most frequently used chemometric method for the calculation of process models and prediction of process variables.

Fluorescence Spectroscopy and Chemometric Modeling for Bioprocess Monitoring

Science.gov (United States)

Faassen, Saskia M.; Hitzmann, Bernd

2015-01-01

On-line sensors for the detection of crucial process parameters are desirable for the monitoring, control and automation of processes in the biotechnology, food and pharma industry. Fluorescence spectroscopy as a highly developed and non-invasive technique that enables the on-line measurements of substrate and product concentrations or the identification of characteristic process states. During a cultivation process significant changes occur in the fluorescence spectra. By means of chemometric modeling, prediction models can be calculated and applied for process supervision and control to provide increased quality and the productivity of bioprocesses. A range of applications for different microorganisms and analytes has been proposed during the last years. This contribution provides an overview of different analysis methods for the measured fluorescence spectra and the model-building chemometric methods used for various microbial cultivations. Most of these processes are observed using the BioView® Sensor, thanks to its robustness and insensitivity to adverse process conditions. Beyond that, the PLS-method is the most frequently used chemometric method for the calculation of process models and prediction of process variables. PMID:25942644

Efficient Generic Functional Programming

NARCIS (Netherlands)

Alimarine, A.; Smetsers, J.E.W.

2005-01-01

Generic functions are defined by induction on the structural representation of types. As a consequence, by defining just a single generic operation, one acquires this operation over any particular data type. An instance on a specific type is generated by interpretation of the type's structure. A

Generic robot architecture

Science.gov (United States)

Bruemmer, David J [Idaho Falls, ID; Few, Douglas A [Idaho Falls, ID

2010-09-21

The present invention provides methods, computer readable media, and apparatuses for a generic robot architecture providing a framework that is easily portable to a variety of robot platforms and is configured to provide hardware abstractions, abstractions for generic robot attributes, environment abstractions, and robot behaviors. The generic robot architecture includes a hardware abstraction level and a robot abstraction level. The hardware abstraction level is configured for developing hardware abstractions that define, monitor, and control hardware modules available on a robot platform. The robot abstraction level is configured for defining robot attributes and provides a software framework for building robot behaviors from the robot attributes. Each of the robot attributes includes hardware information from at least one hardware abstraction. In addition, each robot attribute is configured to substantially isolate the robot behaviors from the at least one hardware abstraction.

42 CFR 447.506 - Authorized generic drugs.

Science.gov (United States)

2010-10-01

... 42 Public Health 4 2010-10-01 2010-10-01 false Authorized generic drugs. 447.506 Section 447.506... (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PAYMENTS FOR SERVICES Payment for Drugs § 447.506 Authorized generic drugs. (a) Authorized generic drug defined. For the purposes of this subpart, an authorized generic drug...

Generic phytosanitary irradiation treatments

International Nuclear Information System (INIS)

Hallman, Guy J.

2012-01-01

The history of the development of generic phytosanitary irradiation (PI) treatments is discussed beginning with its initial proposal in 1986. Generic PI treatments in use today are 150 Gy for all hosts of Tephritidae, 250 Gy for all arthropods on mango and papaya shipped from Australia to New Zealand, 300 Gy for all arthropods on mango shipped from Australia to Malaysia, 350 Gy for all arthropods on lychee shipped from Australia to New Zealand and 400 Gy for all hosts of insects other than pupae and adult Lepidoptera shipped to the United States. Efforts to develop additional generic PI treatments and reduce the dose for the 400 Gy treatment are ongoing with a broad based 5-year, 12-nation cooperative research project coordinated by the joint Food and Agricultural Organization/International Atomic Energy Agency Program on Nuclear Techniques in Food and Agriculture. Key groups identified for further development of generic PI treatments are Lepidoptera (eggs and larvae), mealybugs and scale insects. A dose of 250 Gy may suffice for these three groups plus others, such as thrips, weevils and whiteflies. - Highlights: ► The history of phytosanitary irradiation (PI) treatments is given. ► Generic PI treatments in use today are discussed. ► Suggestions for future research are presented. ► A dose of 250 Gy for most insects may suffice.

Determinants of generic drug substitution in Switzerland

Directory of Open Access Journals (Sweden)

Lufkin Thomas M

2011-01-01

Full Text Available Abstract Background Since generic drugs have the same therapeutic effect as the original formulation but at generally lower costs, their use should be more heavily promoted. However, a considerable number of barriers to their wider use have been observed in many countries. The present study examines the influence of patients, physicians and certain characteristics of the generics' market on generic substitution in Switzerland. Methods We used reimbursement claims' data submitted to a large health insurer by insured individuals living in one of Switzerland's three linguistic regions during 2003. All dispensed drugs studied here were substitutable. The outcome (use of a generic or not was modelled by logistic regression, adjusted for patients' characteristics (gender, age, treatment complexity, substitution groups and with several variables describing reimbursement incentives (deductible, co-payments and the generics' market (prices, packaging, co-branded original, number of available generics, etc.. Results The overall generics' substitution rate for 173,212 dispensed prescriptions was 31%, though this varied considerably across cantons. Poor health status (older patients, complex treatments was associated with lower generic use. Higher rates were associated with higher out-of-pocket costs, greater price differences between the original and the generic, and with the number of generics on the market, while reformulation and repackaging were associated with lower rates. The substitution rate was 13% lower among hospital physicians. The adoption of the prescribing practices of the canton with the highest substitution rate would increase substitution in other cantons to as much as 26%. Conclusions Patient health status explained a part of the reluctance to substitute an original formulation by a generic. Economic incentives were efficient, but with a moderate global effect. The huge interregional differences indicated that prescribing behaviours and

Generic clearance values

International Nuclear Information System (INIS)

Bossio, M.C.; Muniz, C.C.

2009-01-01

This paper analyzes the Generic Clearance Values established for natural and artificial radionuclides with the objective of evaluating their degree of conservatism in views of adopting them into the regulatory body. Generic clearance values for natural radionuclides have been chosen by experts judgments as the optimum boundary between, on one hand, the ubiquitous unmodified soil concentrations and, on the other hand, activity concentrations in ores, mineral sands, industrial residues and wastes. For artificial radionuclides the clearance levels have been derived from the scenarios postulated in the document 'Safety Reports Series Nr 44' of the IAEA considering quantitative exemption criteria. A set of 8 scenarios were postulated covering external, ingestion and inhalation exposure pathways. For each radionuclide, the generic clearance level was derived as the more restrictive value obtained from the scenarios, that is the lowest ratio between the applicable individual dose and the dose per unit activity concentration (Bq/g). The individual dose was calculated by a formula depending on each scenario and pathway, with different parameters, such as exposure time, dosimetric factors, dilution factor, density of the material, geometric factors, etc. It was concluded that the basis and parameters used for the derivation of the generic clearance levels are quite conservative and therefore its the adoption in Argentina has been recommended. It is expected that their implementation will contribute to optimize the regulatory management system. (author)

Generic Clearance Values

International Nuclear Information System (INIS)

Bossio, M.C.; Muniz, C.C.

2010-01-01

This paper analyzes the Generic Clearance Values established for natural and artificial radionuclides with the objective of evaluating their degree of conservatism in views of adopting them into the regulatory body. Generic clearance values for natural radionuclides have been chosen by experts judgments as the optimum boundary between, on the one hand, the ubiquitous unmodified soil concentrations and, on the other hand, activity concentrations in ores, mineral sands, industrial residues and wastes. For artificial radionuclides the clearance levels have been derived from the scenarios postulated in the document Safety Reports Series 44 of the IAEA considering quantitative exemption criteria. A set of 8 scenarios were postulated covering external, ingestion and inhalation exposure pathways. For each radionuclide, the generic clearance level was derived as the more restrictive value obtained from the scenarios, that is the lowest ratio between the applicable individual dose and the dose per unit activity concentration (Bq/g). The individual dose was calculated by a formula depending on each scenario and pathway, with different parameters, such as exposure time, dosimetric factors, dilution factor, density of the material, geometric factors, etc. It was concluded that the basis and parameters used for the derivation of the generic clearance levels are quite conservative and therefore its the adoption in Argentina has been recommended. It is expected that their implementation will contribute to optimize the regulatory management system. (authors) [es

Generic phytosanitary irradiation treatments

Energy Technology Data Exchange (ETDEWEB)

Hallman, Guy J [United States Department of Agriculture, Agricultural Research Service, Weslaco, TX (United States)

2013-01-15

The history of the development of generic phytosanitary irradiation (PI) treatments is discussed beginning with its initial proposal in 1986. Generic PI treatments in use today are 150 Gy for all hosts of Tephritidae, 250 Gy for all arthropods on mango and papaya shipped from Australia to New Zealand, 300 Gy for all arthropods on mango shipped from Australia to Malaysia, 350 Gy for all arthropods on lychee shipped from Australia to New Zealand and 400 Gy for all hosts of insects other than pupae and adult Lepidoptera shipped to the United States. Efforts to develop additional generic PI treatments and reduce the dose for the 400 Gy treatment are ongoing with a broad based 5-year, 12-nation cooperative research project coordinated by the joint Food and Agricultural Organization/International Atomic Energy Agency Program on Nuclear Techniques in Food and Agriculture. Key groups identified for further development of generic PI treatments are Lepidoptera (eggs and larvae), mealybugs and scale insects. A dose of 250 Gy may suffice for these three groups plus others, such as thrips, weevils and whiteflies. (author)

Generic phytosanitary irradiation treatments

Science.gov (United States)

Hallman, Guy J.

2012-07-01

The history of the development of generic phytosanitary irradiation (PI) treatments is discussed beginning with its initial proposal in 1986. Generic PI treatments in use today are 150 Gy for all hosts of Tephritidae, 250 Gy for all arthropods on mango and papaya shipped from Australia to New Zealand, 300 Gy for all arthropods on mango shipped from Australia to Malaysia, 350 Gy for all arthropods on lychee shipped from Australia to New Zealand and 400 Gy for all hosts of insects other than pupae and adult Lepidoptera shipped to the United States. Efforts to develop additional generic PI treatments and reduce the dose for the 400 Gy treatment are ongoing with a broad based 5-year, 12-nation cooperative research project coordinated by the joint Food and Agricultural Organization/International Atomic Energy Agency Program on Nuclear Techniques in Food and Agriculture. Key groups identified for further development of generic PI treatments are Lepidoptera (eggs and larvae), mealybugs and scale insects. A dose of 250 Gy may suffice for these three groups plus others, such as thrips, weevils and whiteflies.

Generic Advantages

Indian Academy of Sciences (India)

First page Back Continue Last page Overview Graphics. Generic Advantages. Scalability an incremental coverage. Standardization. Business Plan Flexibility. Lifecycle Flexibility. Reliability. Service Interoperability. Changed Industry dynamics.

Generic penetration in the retail antidepressant market.

Science.gov (United States)

Ventimiglia, Jeffrey; Kalali, Amir H

2010-06-01

In this article, we explore the accelerated penetration of generic antidepressants in the United States market following the availability of generic citalopram and sertraline. Analysis suggests that overall, generic penetration into the antidepressant market has grown from approximately 41 percent in January 2004 to over 73 percent in January 2010. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty.

Bioprocessing applications in the management of nuclear and chemical wastes

International Nuclear Information System (INIS)

Genung, R.K.

1989-01-01

The US Department of Energy (DOE), the US Department of Defense (DOD), and other federal agencies already face profound challenges in finding strategies that manage budgets and priorities while bringing their sites and facilities into compliance with current statues and regulations and with agency policies and orders. While it is often agreed that current technology can be used to address most waste management and environmental restoration needs, it is also argued by many that the costs of implementing current technology will be too high unless the standards and schedules for compliance are relaxed. Since this is socially unacceptable, efforts to improve the efficiency of existing technologies and to develop new technologies should be pursued. A sizable research, development, and demonstration effort can be easily justified if the potential for reducing costs can be shown. Bioprocessing systems for the treatment of nuclear and chemically hazardous wastes offer such promise

RetroTransformDB: A Dataset of Generic Transforms for Retrosynthetic Analysis

Directory of Open Access Journals (Sweden)

Svetlana Avramova

2018-04-01

Full Text Available Presently, software tools for retrosynthetic analysis are widely used by organic, medicinal, and computational chemists. Rule-based systems extensively use collections of retro-reactions (transforms. While there are many public datasets with reactions in synthetic direction (usually non-generic reactions, there are no publicly-available databases with generic reactions in computer-readable format which can be used for the purposes of retrosynthetic analysis. Here we present RetroTransformDB—a dataset of transforms, compiled and coded in SMIRKS line notation by us. The collection is comprised of more than 100 records, with each one including the reaction name, SMIRKS linear notation, the functional group to be obtained, and the transform type classification. All SMIRKS transforms were tested syntactically, semantically, and from a chemical point of view in different software platforms. The overall dataset design and the retrosynthetic fitness were analyzed and curated by organic chemistry experts. The RetroTransformDB dataset may be used by open-source and commercial software packages, as well as chemoinformatics tools.

Advances in consolidated bioprocessing systems for bioethanol and butanol production from biomass: a comprehensive review

Directory of Open Access Journals (Sweden)

Gholamreza Salehi Jouzani

2015-03-01

Full Text Available Recently, lignocellulosic biomass as the most abundant renewable resource has been widely considered for bioalcohols production. However, the complex structure of lignocelluloses requires a multi-step process which is costly and time consuming. Although, several bioprocessing approaches have been developed for pretreatment, saccharification and fermentation, bioalcohols production from lignocelluloses is still limited because of the economic infeasibility of these technologies. This cost constraint could be overcome by designing and constructing robust cellulolytic and bioalcohols producing microbes and by using them in a consolidated bioprocessing (CBP system. This paper comprehensively reviews potentials, recent advances and challenges faced in CBP systems for efficient bioalcohols (ethanol and butanol production from lignocellulosic and starchy biomass. The CBP strategies include using native single strains with cellulytic and alcohol production activities, microbial co-cultures containing both cellulytic and ethanologenic microorganisms, and genetic engineering of cellulytic microorganisms to be alcohol-producing or alcohol producing microorganisms to be cellulytic. Moreover, high-throughput techniques, such as metagenomics, metatranscriptomics, next generation sequencing and synthetic biology developed to explore novel microorganisms and powerful enzymes with high activity, thermostability and pH stability are also discussed. Currently, the CBP technology is in its infant stage, and ideal microorganisms and/or conditions at industrial scale are yet to be introduced. So, it is essential to bring into attention all barriers faced and take advantage of all the experiences gained to achieve a high-yield and low-cost CBP process.

Implementation and use of cloud-based electronic lab notebook in a bioprocess engineering teaching laboratory.

Science.gov (United States)

Riley, Erin M; Hattaway, Holly Z; Felse, P Arthur

2017-01-01

Electronic lab notebooks (ELNs) are better equipped than paper lab notebooks (PLNs) to handle present-day life science and engineering experiments that generate large data sets and require high levels of data integrity. But limited training and a lack of workforce with ELN knowledge have restricted the use of ELN in academic and industry research laboratories which still rely on cumbersome PLNs for recordkeeping. We used LabArchives, a cloud-based ELN in our bioprocess engineering lab course to train students in electronic record keeping, good documentation practices (GDPs), and data integrity. Implementation of ELN in the bioprocess engineering lab course, an analysis of user experiences, and our development actions to improve ELN training are presented here. ELN improved pedagogy and learning outcomes of the lab course through stream lined workflow, quick data recording and archiving, and enhanced data sharing and collaboration. It also enabled superior data integrity, simplified information exchange, and allowed real-time and remote monitoring of experiments. Several attributes related to positive user experiences of ELN improved between the two subsequent years in which ELN was offered. Student responses also indicate that ELN is better than PLN for compliance. We demonstrated that ELN can be successfully implemented in a lab course with significant benefits to pedagogy, GDP training, and data integrity. The methods and processes presented here for ELN implementation can be adapted to many types of laboratory experiments.

Rethinking generic skills

Directory of Open Access Journals (Sweden)

Roy Canning

2013-10-01

Full Text Available The paper provides a critical analysis of the notion of generic or transversal skillscontained with European Union policy discourses. The author presents a conceptualframework that challenges the idea that generic skills are universal, transferable andautonomous. An alternative analysis is put forward that argues the case forcontextualising skills and knowledge within particular understandings and cultures thatare more collective than individualistic in nature. The arguments are framed withinwider cross-disciplinary debates in linguistics, geosemiotics and social-cultural theoryand build upon an earlier paper exploring core skills in the UK (Canning, 2007.

Quality of generic medicines in South Africa

DEFF Research Database (Denmark)

Patel, Aarti; Gauld, Robin; Norris, Pauline

2012-01-01

Generic Medicines are an important policy option allowing for access to affordable, essential medicines. Quality of generic medicines must be guaranteed through the activities of national medicines regulatory authorities. Existing negative perceptions surrounding the quality of generic medicines ...

Exploring knowledge, perceptions and attitudes about generic ...

African Journals Online (AJOL)

Exploring knowledge, perceptions and attitudes about generic medicines among final-year health science students. ... had knowledge deficits about the safety, quality and efficacy of generic medicines. The dissemination of information about generic medicines may strengthen future knowledge, attitudes and perceptions.

Dynamics of complex interconnected systems: Networks and bioprocesses[A NATO study seminary

Energy Technology Data Exchange (ETDEWEB)

Wilhelmsen, Line K

2005-07-01

Rapid detection of chemical and biological agents and weapons, and rapid diagnosis of their effects on people will require molecular recognition as well as signal discrimination, i.e. avoiding false positives and negatives, and signal transduction. It will be important to have reagentless, cheap, easily manufactured sensors that can be field deployed in large numbers. While this problem is urgent it is not yet solved. This ASI brought together researchers with various interests and background including theoretical physicists, soft condensed matter experimentalists, biological physicists, and molecular biologists to identify and discuss areas where synergism between modem physics and biology may be most fruitfully applied to the study of bioprocesses for molecular recognition and of networks for converting molecular reactions into usable signals and appropriate responses. (Author)

Generic medicines: Perceptions of Physicians in Basrah, Iraq

Directory of Open Access Journals (Sweden)

Adheed Khalid Sharrad

2009-08-01

Full Text Available BackgroundThe use of cheaper generic medicines is a strategy promotedin many countries to reduce rising health care costs. The aimof this study was to explore factors affecting generic medicineprescribing by physicians in Basrah, Iraq.MethodologyA purposive sample of ten physicians practicing in Basrahwas interviewed using a semi-structured interview guide.ResultsAnalysis of the interviews identified seven major themes:medicine prescribing practice, knowledge of therapeuticequivalency of generic medicine, patients’ acceptance ofgeneric medicine, counterfeit medicine, drug informationsource and effect of drug advertising on medicines choice,brand substitution practice by community pharmacists, and,finally strategies to improve generic medicine usefulness.Participants identified helpful strategies to increase genericprescribing including; physician and patient education ongeneric medicine; persuading physicians about the safety andefficacy of generic medicines; and finally educating seniormedical students on generic prescribing.ConclusionThe data suggest that participants were enthusiasticabout prescribing generic medicines. However physiciansinsist that pharmacists should not be allowed tosubstitute generic drugs without prior approval ofdoctors.

Comparing approaches to generic programming in Haskell

NARCIS (Netherlands)

Hinze, R.; Jeuring, J.T.; Löh, A.

2006-01-01

The last decade has seen a number of approaches to generic programming: PolyP, Functorial ML, `Scrap Your Boilerplate', Generic Haskell, `Generics for the Masses', etc. The approaches vary in sophistication and target audience: some propose full-blown pro- gramming languages, some suggest

Generic Switching and Non-Persistence among Medicine Users

DEFF Research Database (Denmark)

Østergaard Rathe, Jette; Andersen, Morten; Jarbøl, Dorte Ejg

2015-01-01

BACKGROUND: Generic substitution means that one medicinal product is replaced by another product containing the same active substance. It is strictly regulated with respect to its bioequivalence, and all products must have undergone appropriate studies. Although generic substitution is widely...... implemented, it still remains to be answered how generic switch influences persistence to long-term treatment, and if it is modified by patients' concerns about medicine and views on generic medicine. This study focuses on users of antidepressants and antiepileptics, and their experience of generic switching....... METHODS: The study was an observational cohort study. By use of a prescription database, we identified patients who had redeemed prescriptions on generically substitutable drugs, and a questionnaire was mailed to them. We analyzed predictors of discontinuation in relation to generic switch and patients...

Article choice in plural generics

NARCIS (Netherlands)

Farkas, D.F.; Swart, Henriëtte de

2007-01-01

We discuss two groups of languages where article use contrasts in generic plural sentences but is otherwise essentially similar. The languages in the first group (English and Dutch) use bare plurals in the expression of kind reference (‘Dinosaurs are extinct’) and in generic

40 CFR 721.9973 - Zirconium dichlorides (generic).

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Zirconium dichlorides (generic). 721... Substances § 721.9973 Zirconium dichlorides (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as zirconium dichlorides (PMNs P...

Comparing approaches to generic programming in Haskell

NARCIS (Netherlands)

Hinze, R.; Jeuring, J.T.; Löh, A.

2006-01-01

The last decade has seen a number of approaches to data- type-generic programming: PolyP, Functorial ML, `Scrap Your Boiler- plate', Generic Haskell, `Generics for the Masses', etc. The approaches vary in sophistication and target audience: some propose full-blown pro- gramming languages, some

40 CFR 721.9959 - Polyurethane polymer (generic).

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Polyurethane polymer (generic). 721... Substances § 721.9959 Polyurethane polymer (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as a polyurethane polymer (PMN P-01...

Proceedings Workshop on Generic Programming (WGP2000)

NARCIS (Netherlands)

Jeuring, J.T.

2000-01-01

This report contains the papers selected for presentation at the 2nd Workshop on Generic Programming (WGP2000), which was held on July 6, 2000 in Ponte de Lima, Portugal. Generic programming is about making programs more adaptable by making them more general. Generic programs often embody

Skin rash during treatment with generic itraconazole.

Science.gov (United States)

De Vuono, Antonio; Palleria, Caterina; Scicchitano, Francesca; Squillace, Aida; De Sarro, Giovambattista; Gallelli, Luca

2014-04-01

Generic drugs have the same active substance, the same pharmaceutical form, the same therapeutic indications and a similar bioequivalence with the reference medicinal product (branded). Although a similar efficacy is postulated, some cases of clinical inefficacy during treatment with generic formulations have been reported. In this case, we describe a woman with onychomycosis that developed a skin rash during treatment with a generic formulation of itraconazole. Drug administration and its re-challenge confirmed the association between itraconazole and skin rash. Both Naranjo probability scale and World Health Organization causality assessment scale documented a probable association between generic-itraconazole and skin rash. The switch from generic formulation to brand one induced an improvement of symptoms. Since we are unable to evaluate the role of each excipient in the development of skin rash, we cannot rule out their involvement. However, more data are necessary to better define the similarities or differences between branded and generic formulations.

Is bioavailability altered in generic versus brand anticonvulsants?

Science.gov (United States)

Jankovic, Slobodan M; Ignjatovic Ristic, Dragana

2015-03-01

Therapeutic window of anticonvulsants is not a wide one, with phenytoin being one extreme, which can be classified as a narrow therapeutic index drug, since its ratio between the least toxic and the least effective concentration is less than twofold. In order to obtain marketing authorization, a generic anticonvulsant should demonstrate relative bioequivalence with its brand-name counterpart. However, although bioequivalent, generic anticonvulsants still do not have the same bioavailability as brand-name drugs, which may lead to larger fluctuations of steady-state plasma concentrations, and sometimes to loss of seizure control if a patient is switched from brand-name to generic or from generic to generic anticonvulsant. Generic anticonvulsants are effective, safe and affordable drugs for treatment of epilepsy, and patients could be successfully treated with them from the very beginning. It is switching from brand-name to generic anticonvulsant or from one generic anticonvulsant to another that should be avoided in clinical practice, since subtle differences in bioavailability may disturb optimal degree of seizure control to which the patient was previously successfully titrated.

A generic high-dose rate {sup 192}Ir brachytherapy source for evaluation of model-based dose calculations beyond the TG-43 formalism

Energy Technology Data Exchange (ETDEWEB)

Ballester, Facundo, E-mail: Facundo.Ballester@uv.es [Department of Atomic, Molecular and Nuclear Physics, University of Valencia, Burjassot 46100 (Spain); Carlsson Tedgren, Åsa [Department of Medical and Health Sciences (IMH), Radiation Physics, Faculty of Health Sciences, Linköping University, Linköping SE-581 85, Sweden and Department of Medical Physics, Karolinska University Hospital, Stockholm SE-171 76 (Sweden); Granero, Domingo [Department of Radiation Physics, ERESA, Hospital General Universitario, Valencia E-46014 (Spain); Haworth, Annette [Department of Physical Sciences, Peter MacCallum Cancer Centre and Royal Melbourne Institute of Technology, Melbourne, Victoria 3000 (Australia); Mourtada, Firas [Department of Radiation Oncology, Helen F. Graham Cancer Center, Christiana Care Health System, Newark, Delaware 19713 (United States); Fonseca, Gabriel Paiva [Instituto de Pesquisas Energéticas e Nucleares – IPEN-CNEN/SP, São Paulo 05508-000, Brazil and Department of Radiation Oncology (MAASTRO), GROW, School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht 6201 BN (Netherlands); Zourari, Kyveli; Papagiannis, Panagiotis [Medical Physics Laboratory, Medical School, University of Athens, 75 MikrasAsias, Athens 115 27 (Greece); Rivard, Mark J. [Department of Radiation Oncology, Tufts University School of Medicine, Boston, Massachusetts 02111 (United States); Siebert, Frank-André [Clinic of Radiotherapy, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel 24105 (Germany); Sloboda, Ron S. [Department of Medical Physics, Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada and Department of Oncology, University of Alberta, Edmonton, Alberta T6G 2R3 (Canada); and others

2015-06-15

Purpose: In order to facilitate a smooth transition for brachytherapy dose calculations from the American Association of Physicists in Medicine (AAPM) Task Group No. 43 (TG-43) formalism to model-based dose calculation algorithms (MBDCAs), treatment planning systems (TPSs) using a MBDCA require a set of well-defined test case plans characterized by Monte Carlo (MC) methods. This also permits direct dose comparison to TG-43 reference data. Such test case plans should be made available for use in the software commissioning process performed by clinical end users. To this end, a hypothetical, generic high-dose rate (HDR) {sup 192}Ir source and a virtual water phantom were designed, which can be imported into a TPS. Methods: A hypothetical, generic HDR {sup 192}Ir source was designed based on commercially available sources as well as a virtual, cubic water phantom that can be imported into any TPS in DICOM format. The dose distribution of the generic {sup 192}Ir source when placed at the center of the cubic phantom, and away from the center under altered scatter conditions, was evaluated using two commercial MBDCAs [Oncentra{sup ®} Brachy with advanced collapsed-cone engine (ACE) and BrachyVision ACUROS{sup TM}]. Dose comparisons were performed using state-of-the-art MC codes for radiation transport, including ALGEBRA, BrachyDose, GEANT4, MCNP5, MCNP6, and PENELOPE2008. The methodologies adhered to recommendations in the AAPM TG-229 report on high-energy brachytherapy source dosimetry. TG-43 dosimetry parameters, an along-away dose-rate table, and primary and scatter separated (PSS) data were obtained. The virtual water phantom of (201){sup 3} voxels (1 mm sides) was used to evaluate the calculated dose distributions. Two test case plans involving a single position of the generic HDR {sup 192}Ir source in this phantom were prepared: (i) source centered in the phantom and (ii) source displaced 7 cm laterally from the center. Datasets were independently produced by

A multicenter experience with generic tacrolimus conversion.

Science.gov (United States)

McDevitt-Potter, Lisa M; Sadaka, Basma; Tichy, Eric M; Rogers, Christin C; Gabardi, Steven

2011-09-27

The first generic tacrolimus product gained Food and Drug Administration approval in August 2009. This prospective, observational trial sought to determine the need for dose titrations and measure drug cost savings on conversion to generic tacrolimus. Transplant recipients on stable tacrolimus doses were converted from brand to generic tacrolimus on a mg:mg basis. Data were collected at the time of generic conversion (study arm) and at a time point exactly 6 months before conversion (control arm) for all subjects. Seventy conversions from four centers are reported. Subjects were a mean of 70 months after kidney (n=37), liver (n=28), or multiorgan (n=5) transplant. In the study arm, mean tacrolimus doses were 4.4 and 4.5 mg/d and mean tacrolimus trough concentrations were 5.8 and 5.9 ng/mL before and after conversion, respectively. In the control arm, mean tacrolimus doses were 4.6 and 4.6 mg/d and mean tacrolimus trough concentrations were 6.1 and 5.9 ng/mL before and after the control time point, respectively. Dose titrations occurred in five patients (7%) in the control arm and 15 patients (21%) in the study arm (P=0.028). Mean monthly drug costs were $645 for brand, $593 for generic, and $595 for generic after dose titrations. Mean monthly patient copays were $38 for brand and $15 for generic. These cumulative data show that dose requirements and trough levels are similar between brand and generic tacrolimus and that generic substitution allows for savings. However, postconversion monitoring is prudent as patients may require dose titration.

Brand loyalty, patients and limited generic medicines uptake.

Science.gov (United States)

Costa-Font, Joan; Rudisill, Caroline; Tan, Stefanie

2014-06-01

The sluggish development of European generic drug markets depends heavily on demand side factors, and more specifically, patients' and doctors' loyalty to branded products. Loyalty to originator drugs, to the point where originator prices rise upon generic entry has been described as the 'generics paradox'. Originator loyalty can emerge for a plethora of reasons; including costs, perceptions about quality and physician advice. We know very little about the behavioural underpinnings of brand loyalty from the consumer or patient standpoint. This paper attempts to test the extent to which patients are brand loyal by drawing upon Spain's 2002 Health Barometer survey as it includes questions about consumer acceptance of generics in a country with exceptionally low generic uptake and substitution at the time of the study. Our findings suggest that at least 13% of the population would not accept generics as substitutes to the originator. These results confirm evidence of brand loyalty for a minority. Alongside high levels of awareness of generics, we find that low cost-sharing levels explain consumer brand loyalty but their impact on acceptance of generic substitution is very small. Higher cost-sharing and exempting fewer patients from cost-sharing have the potential to encourage generic acceptance. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Influencers of generic drug utilization: A systematic review.

Science.gov (United States)

Howard, Jennifer N; Harris, Ilene; Frank, Gavriella; Kiptanui, Zippora; Qian, Jingjing; Hansen, Richard

2017-08-04

With an increase in prescription drug spending and rising drug costs there is a need to encourage the use of generic prescription drugs. However, maximizing generic drug use is not possible without the public's positive perception and meeting their informational needs about generic drugs. Thus, improving the public's confidence in, and knowledge of generic drugs on the market is critical. The objective of this systematic review is to examine and evaluate the studies focusing on the nature and extent of key factors influencing generic drug use in the United States in order to help guide policy, education and practice interventions. Using multiple search engines and key word screening criteria, empirical studies published in English between January 1, 2005 and December 31, 2015 were identified. A qualitative synthesis of the evidence identified domains of key factors that influenced generic drug use across studies. Over 3000 citations met the key word screening criteria; 67 of these met inclusion criteria for the systematic review. Seven domains of factors that influence generic drug utilization were identified: 1) patient-related factors, 2) formulary management or cost containment, 3) healthcare policies, 4) promotional activities, 5) educational initiatives, 6) technology, and 7) physician-related factors. Patients, physicians, pharmacists, formulary managers, and policymakers play an important role in generic drug use. Understanding the factors influencing generic drug use can help guide future policy, education, and practice interventions to increase generic drug use. Copyright © 2017 Elsevier Inc. All rights reserved.

Generic domain models in software engineering

Science.gov (United States)

Maiden, Neil

1992-01-01

This paper outlines three research directions related to domain-specific software development: (1) reuse of generic models for domain-specific software development; (2) empirical evidence to determine these generic models, namely elicitation of mental knowledge schema possessed by expert software developers; and (3) exploitation of generic domain models to assist modelling of specific applications. It focuses on knowledge acquisition for domain-specific software development, with emphasis on tool support for the most important phases of software development.

Scale-up bioprocess development for production of the antibiotic valinomycin in Escherichia coli based on consistent fed-batch cultivations.

Science.gov (United States)

Li, Jian; Jaitzig, Jennifer; Lu, Ping; Süssmuth, Roderich D; Neubauer, Peter

2015-06-12

Heterologous production of natural products in Escherichia coli has emerged as an attractive strategy to obtain molecules of interest. Although technically feasible most of them are still constrained to laboratory scale production. Therefore, it is necessary to develop reasonable scale-up strategies for bioprocesses aiming at the overproduction of targeted natural products under industrial scale conditions. To this end, we used the production of the antibiotic valinomycin in E. coli as a model system for scalable bioprocess development based on consistent fed-batch cultivations. In this work, the glucose limited fed-batch strategy based on pure mineral salt medium was used throughout all scales for valinomycin production. The optimal glucose feed rate was initially detected by the use of a biocatalytically controlled glucose release (EnBase® technology) in parallel cultivations in 24-well plates with continuous monitoring of pH and dissolved oxygen. These results were confirmed in shake flasks, where the accumulation of valinomycin was highest when the specific growth rate decreased below 0.1 h(-1). This correlation was also observed for high cell density fed-batch cultivations in a lab-scale bioreactor. The bioreactor fermentation produced valinomycin with titers of more than 2 mg L(-1) based on the feeding of a concentrated glucose solution. Valinomycin production was not affected by oscillating conditions (i.e. glucose and oxygen) in a scale-down two-compartment reactor, which could mimic similar situations in industrial bioreactors, suggesting that the process is very robust and a scaling of the process to a larger industrial scale appears a realistic scenario. Valinomycin production was scaled up from mL volumes to 10 L with consistent use of the fed-batch technology. This work presents a robust and reliable approach for scalable bioprocess development and represents an example for the consistent development of a process for a heterologously expressed natural

Public comments on the draft generic environmental impact statement for management of commercially generated radioactive waste

International Nuclear Information System (INIS)

Kreiter, M.R.; Unruh, C.M.; McCallum, R.F.

1980-01-01

The US Department of Energy has the responsibility for developing the technology required for managing commercial radioactive wastes in an environmentally acceptable manner. As part of this responsibility, DOE has prepared a draft environmental impact statement on the management of commercially generated radioactive waste. The draft was issued for public comment in April of 1979; five public hearings were held. The draft GEIS is intended to provide environmental input for the selection of an appropriate program strategy for the permanent isolation of commercially generated high-level and transuranic wastes. The scope of such a strategy includes research and development into alternative treatment processes and emplacement media, site investigations into candidate media, and the examination of advanced waste management technologies. The draft statement describes the commercial radioactive wastes that would have to be managed for very long periods of time from an assumed nuclear generation scenario of 10,000 GWe-yr of power over a 65-year period ending in 2040

Integrating Cellular and Bioprocess Engineering in the Non-Conventional Yeast Yarrowia lipolytica for Biodiesel Production: A Review

Directory of Open Access Journals (Sweden)

Dongming Xie

2017-10-01

Full Text Available As one of the major biofuels to replace fossil fuel, biodiesel has now attracted more and more attention due to its advantages in higher energy density and overall less greenhouse gas generation. Biodiesel (fatty acid alkyl esters is produced by chemically or enzymatically catalyzed transesterification of lipids from microbial cells, microalgae, oil crops, or animal fats. Currently, plant oils or waste cooking oils/fats remain the major source for biodiesel production via enzymatic route, but the production capacity is limited either by the uncertain supplement of plant oils or by the low or inconsistent quality of waste oils/fats. In the past decades, significant progresses have been made on synthesis of microalgae oils directly from CO2via a photosynthesis process, but the production cost from any current technologies is still too high to be commercialized due to microalgae’s slow growth rate on CO2, inefficiency in photo-bioreactors, lack of efficient contamination control methods, and high cost in downstream recovery. At the same time, many oleaginous microorganisms have been studied to produce lipids via the fatty acid synthesis pathway under aerobic fermentation conditions, among them one of the most studied is the non-conventional yeast, Yarrowia lipolytica, which is able to produce fatty acids at very high titer, rate, and yield from various economical substrates. This review summarizes the recent research progresses in both cellular and bioprocess engineering in Y. lipolytica to produce lipids at a low cost that may lead to commercial-scale biodiesel production. Specific technologies include the strain engineering for using various substrates, metabolic engineering in high-yield lipid synthesis, cell morphology study for efficient substrate uptake and product formation, free fatty acid formation and secretion for improved downstream recovery, and fermentation engineering for higher productivities and less operating cost. To further

76 FR 54507 - Proposed Generic Communication; Draft NRC Generic Letter 2011-XX: Seismic Risk Evaluations for...

Science.gov (United States)

2011-09-01

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0204] Proposed Generic Communication; Draft NRC Generic... functions. SSCs in operating nuclear power plants are designed either in accordance with, or have been... nuclear reactors. The background information relevant to this GL includes the individual plant...

Practicing the Generic (City)

DEFF Research Database (Denmark)

Hansen, Lone Koefoed

2010-01-01

Flanagan proposes that most locative media artworks neglect the particularities of spaces, their historical and political layers. Koolhaas, on the other hand, states that all urban areas are alike, that we are facing a global Generic City. The paper analyses digital media artist Esther Polak......’s NomadicMILK project in light of the generic and particular properties of space as laid out by Flanagan and Koolhaas in order to discuss the possible reconfiguring practices of locative media....

Brand and generic medications: Are they interchangeable

International Nuclear Information System (INIS)

Al-Jazairi, Abdulrazak S.; Blhareth, S.; Eqtefan, Iyad S.; Al-Suwayeh, Saleh A.

2008-01-01

Generic substitution has become a common practice since the late 1970s in the United States. At that time, many of these generics caused bioavailability problems, which fueled suspicions about their efficacy and safety and the Food and Drug Administration (FDA) standards for bioequivalence. In Saudi Arabia, the increasing number of local products raised several concerns with regard to switching from brands to generics. Our objective was to review and examine the basis of the controversy surrounding brand and generic interchangeability and to explore a practical approach in pursuing a switch. Articles indexed initially under terms such as generic medications, generic substitution, bioequivalence and bioinequivalence were identified. These terms were used to search the indexing service, MEDLINE (1966-2006). References from the extracted articles and additional data sources, including the Code of Federal Regulations and Regulatory Guidelines from the FDA Center for Drug Evaluation and research were also reviewed. Foe most drugs, bioequivalence testing generally should enable clinicians to routinely substitute generic for innovator products. However, for narrow therapeutic, critical dose drugs, or for highly variable drugs, safe switching between products can not be assured. These drugs need special precautions and blood level monitoring upon switching. FDA firmly believes that approved generic and brand drugs can be dispensed with the full expectation that the consumer will receive the same clinical benefit. Performing the switch process is an advisable practice to reduce health care costs in countries with strong post-marketing surveillance program, but caution is to be exercised when narrow therapeutic index drugs or highly variable drugs are prescribed. (author)

New perspectives for the petroleum industry. Bioprocesses for the selective removal of sulphur, nitrogen and metals

International Nuclear Information System (INIS)

Zerlia, T.

2000-01-01

Fuel biocatalytic conversion is a process that removes, through selective enzyme-catalyzed reactions, sulphur, nitrogen and metals. The mild operating conditions, the specificity of reactions and the quality of coproducts (particularly the organo sulphur compounds, a source for the petrochemical industry) are just a few of the attractive aspects of this new technology which could open a new world of possibilities in the technology and in the environmental impact of fuels. The paper shows the state-of-the-art of the research and applications of bioprocesses to the petroleum field [it

An Intelligent Automation Platform for Rapid Bioprocess Design.

Science.gov (United States)

Wu, Tianyi; Zhou, Yuhong

2014-08-01

Bioprocess development is very labor intensive, requiring many experiments to characterize each unit operation in the process sequence to achieve product safety and process efficiency. Recent advances in microscale biochemical engineering have led to automated experimentation. A process design workflow is implemented sequentially in which (1) a liquid-handling system performs high-throughput wet lab experiments, (2) standalone analysis devices detect the data, and (3) specific software is used for data analysis and experiment design given the user's inputs. We report an intelligent automation platform that integrates these three activities to enhance the efficiency of such a workflow. A multiagent intelligent architecture has been developed incorporating agent communication to perform the tasks automatically. The key contribution of this work is the automation of data analysis and experiment design and also the ability to generate scripts to run the experiments automatically, allowing the elimination of human involvement. A first-generation prototype has been established and demonstrated through lysozyme precipitation process design. All procedures in the case study have been fully automated through an intelligent automation platform. The realization of automated data analysis and experiment design, and automated script programming for experimental procedures has the potential to increase lab productivity. © 2013 Society for Laboratory Automation and Screening.

An Intelligent Automation Platform for Rapid Bioprocess Design

Science.gov (United States)

Wu, Tianyi

2014-01-01

Bioprocess development is very labor intensive, requiring many experiments to characterize each unit operation in the process sequence to achieve product safety and process efficiency. Recent advances in microscale biochemical engineering have led to automated experimentation. A process design workflow is implemented sequentially in which (1) a liquid-handling system performs high-throughput wet lab experiments, (2) standalone analysis devices detect the data, and (3) specific software is used for data analysis and experiment design given the user’s inputs. We report an intelligent automation platform that integrates these three activities to enhance the efficiency of such a workflow. A multiagent intelligent architecture has been developed incorporating agent communication to perform the tasks automatically. The key contribution of this work is the automation of data analysis and experiment design and also the ability to generate scripts to run the experiments automatically, allowing the elimination of human involvement. A first-generation prototype has been established and demonstrated through lysozyme precipitation process design. All procedures in the case study have been fully automated through an intelligent automation platform. The realization of automated data analysis and experiment design, and automated script programming for experimental procedures has the potential to increase lab productivity. PMID:24088579

Contact Geometry of Hyperbolic Equations of Generic Type

Directory of Open Access Journals (Sweden)

Dennis The

2008-08-01

Full Text Available We study the contact geometry of scalar second order hyperbolic equations in the plane of generic type. Following a derivation of parametrized contact-invariants to distinguish Monge-Ampère (class 6-6, Goursat (class 6-7 and generic (class 7-7 hyperbolic equations, we use Cartan's equivalence method to study the generic case. An intriguing feature of this class of equations is that every generic hyperbolic equation admits at most a nine-dimensional contact symmetry algebra. The nine-dimensional bound is sharp: normal forms for the contact-equivalence classes of these maximally symmetric generic hyperbolic equations are derived and explicit symmetry algebras are presented. Moreover, these maximally symmetric equations are Darboux integrable. An enumeration of several submaximally symmetric (eight and seven-dimensional generic hyperbolic structures is also given.

Generic penetration in the retail atypical antipsychotic market.

Science.gov (United States)

Lenderts, Susan; Kalali, Amir H; Buckley, Peter

2010-03-01

In this article, we explore the penetration of generic atypical antipsychotics in the United States market before and after the availability of generic risperidone in July 2008. Analysis suggests that, overall, generic penetration into the atypical antipsychotic market has grown from approximately three percent in January 2008 to more than 25 percent in December 2009. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty.

40 CFR 721.2083 - Polysubstituted carbomonocyclic hydroxylamine (generic).

Science.gov (United States)

2010-07-01

... hydroxylamine (generic). 721.2083 Section 721.2083 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.2083 Polysubstituted carbomonocyclic hydroxylamine (generic). (a... generically as a polysubstituted carbomonocyclic hydroxylamine (PMN P-97-878) is subject to reporting under...

Sharing, samples, and generics: an antitrust framework.

Science.gov (United States)

Carrier, Michael A

Rising drug prices are in the news. By increasing price, drug companies have placed vital, even life-saving, medicines out of the reach of consumers. In a recent development, brand firms have prevented generics even from entering the market. The ruse for this strategy involves risk-management programs known as Risk Evaluation and Mitigation Strategies ("REMS"). Pursuant to legislation enacted in 2007, the FDA requires REMS when a drug's risks (such as death or injury) outweigh its rewards. Brands have used this regime, intended to bring drugs to the market, to block generic competition. Regulations such as the federal Hatch-Waxman Act and state substitution laws foster widespread generic competition. But these regimes can only be effectuated through generic entry. And that entry can take place only if a generic can use a brand's sample to show that its product is equivalent. More than 100 generic firms have complained that they have not been able to access needed samples. One study of 40 drugs subject to restricted access programs found that generics' inability to enter cost more than $5 billion a year. Brand firms have contended that antitrust law does not compel them to deal with their competitors and have highlighted concerns related to safety and product liability in justifying their refusals. This Article rebuts these claims. It highlights the importance of samples in the regulatory regime and the FDA's inability to address the issue. It shows how a sharing requirement in this setting is consistent with Supreme Court caselaw. And it demonstrates that the brands' behavior fails the defendant-friendly "no economic sense" test because the conduct literally makes no sense other than by harming generics. Brands' denial of samples offers a textbook case of monopolization. In the universe of pharmaceutical antitrust behavior, other conduct--such as "pay for delay" settlements between brands and generics and "product hopping" from one drug to a slightly modified

Associations between generic substitution and patients' attitudes, beliefs and experience

DEFF Research Database (Denmark)

Østergaard Rathe, Jette; Larsen, Pia Veldt; Andersen, Morten

2013-01-01

Abstract Background Generic substitution has been implemented in many countries, but knowledge about patients’ attitudes, beliefs and experiences is still sparse. Aim To assess associations between generic switching and patients’ attitudes, beliefs and experiences with previous generic switching...... on generic medicine and confidence in the healthcare system. Only prescriptions issued by the general practitioners were included. For each patient we focused on one purchase of a generically substitutable drug (index drug). Patients were identified by means of a dispensing database. Results Earlier generic...... switches within the index ATC code were statistically significantly associated with experience of a generic switch (adjusted OR 5.93 95% CI 4.70; 7.49). Having had more than 5 earlier switches within other ATC codes and having negative views on generic medicines reduced the odds of experiencing a generic...

Generics, Supergenerics and Patent Strategies--SMi's 13th Annual Meeting.

Science.gov (United States)

Edwards, Catherine

2010-07-01

SMi's 13th Annual Meeting on Generics, Supergenerics and Patent Strategies, held in London, included topics covering new trends in the generics field, the difficulties faced by companies in entering the generics market and recent developments in IP. This conference report highlights selected presentations on generics in India, protecting pharmaceutical products in China, changes in generics law and litigation in the US and Europe, challenges for market selection and entry for generics companies, the influence of changes in the healthcare market on the generics industry, supergenerics, and biosimilars.

PROBLEM OF GENERIC REPLACEMENT: ADVANTAGES AND DISADVANTAGES

Directory of Open Access Journals (Sweden)

S. N. Tolpygina

2009-01-01

Full Text Available The main differences between original and generic drugs as well as registration criteria for generics are described. Possible reasons of discrepancy in bioequivalence and therapeutic equivalence of original and generic drugs are reviewed. The examples of such a discrepancy as a result of comparative clinical trails (enalapril maleate are discussed. Approaches to planning of comparative trails on drug therapeutic equivalence are presented. 

A generic coordinate system and a set of generic variables for MFE database

International Nuclear Information System (INIS)

Miner, W.H. Jr.; Ross, D.W.; Solano, E.R.; Valanju, P.M.; Wiley, J.C.

1993-01-01

Over the last several years, profile data from nine different tokamaks have been stored in the magnetic fusion energy database (MFEDB). These data sets have come from a variety of sources and most are given in different coordinate systems. In order to attempt any intermachine analysis, it is convenient to transform these data sets into one generic coordinate system and to choose a uniform set of variable names. The authors describe the data sets from each tokamak indicating the source of the data and the coordinate system in which it is given. Next, they discuss the generic coordinate that has been adopted and show how it is implemented for each tokamak. Finally, the generic naming convention that has been adopted is discussed. It follows closely that which was used by Christiansen et al. for the ITER Global Energy Confinement H-Mode Database. For further clarification, they discuss the characteristics of the magnetic geometry given a Fourier representation of the magnetic equilibria

Generic Software Architecture for Launchers

Science.gov (United States)

Carre, Emilien; Gast, Philippe; Hiron, Emmanuel; Leblanc, Alain; Lesens, David; Mescam, Emmanuelle; Moro, Pierre

2015-09-01

The definition and reuse of generic software architecture for launchers is not so usual for several reasons: the number of European launcher families is very small (Ariane 5 and Vega for these last decades); the real time constraints (reactivity and determinism needs) are very hard; low levels of versatility are required (implying often an ad hoc development of the launcher mission). In comparison, satellites are often built on a generic platform made up of reusable hardware building blocks (processors, star-trackers, gyroscopes, etc.) and reusable software building blocks (middleware, TM/TC, On Board Control Procedure, etc.). If some of these reasons are still valid (e.g. the limited number of development), the increase of the available CPU power makes today an approach based on a generic time triggered middleware (ensuring the full determinism of the system) and a centralised mission and vehicle management (offering more flexibility in the design and facilitating the long term maintenance) achievable. This paper presents an example of generic software architecture which could be envisaged for future launchers, based on the previously described principles and supported by model driven engineering and automatic code generation.

40 CFR 721.324 - Alkoxylated acrylate polymer (generic).

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkoxylated acrylate polymer (generic... Substances § 721.324 Alkoxylated acrylate polymer (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as alkoxylated acrylate polymer...

Generic maintenance immunosuppression in solid organ transplant recipients.

Science.gov (United States)

Ensor, Christopher R; Trofe-Clark, Jennifer; Gabardi, Steven; McDevitt-Potter, Lisa M; Shullo, Michael A

2011-11-01

Survival after solid organ transplantation has increased in the era of tacrolimus and mycophenolate. This increased survival could be due in part to the broad clinical use of these potent and specific agents for maintenance immunosuppression. These drugs have enhanced specificity and potency for T and B lymphocytes compared with their predecessors, cyclosporine and azathioprine. Between 2008 and 2010, the United States Food and Drug Administration approved several generic formulations of both tacrolimus and mycophenolate mofetil. Deciding whether generic products can be safely substituted for the innovator product is a clinical dilemma similar to that which occurred when generic formulations of cyclosporine became available. We describe the concerns regarding generic immunosuppression use, summarize expert opinion and consensus statements in transplantation, analyze the potential impact of generic substitution, and provide estimates of populations affected based on generic drug market penetration. Formulary considerations such as cost, availability, and potential drug ordering and drug selection errors are described, and transplant coordinator and patient perspectives are reviewed. Finally, general recommendations about the use of generic maintenance immunosuppression in solid organ transplant recipients are provided. Although more research is needed to confirm clinical and therapeutic equivalence and pharmacoeconomic benefit, generic immunosuppressants can be safely substituted for innovator products as long as patients consistently receive the same product, patients and clinicians are aware of when substitutions occur, and enhanced therapeutic drug monitoring is provided during the transition.

Skin rash during treatment with generic itraconazole

OpenAIRE

De Vuono, Antonio; Palleria, Caterina; Scicchitano, Francesca; Squillace, Aida; De Sarro, Giovambattista; Gallelli, Luca

2014-01-01

Generic drugs have the same active substance, the same pharmaceutical form, the same therapeutic indications and a similar bioequivalence with the reference medicinal product (branded). Although a similar efficacy is postulated, some cases of clinical inefficacy during treatment with generic formulations have been reported. In this case, we describe a woman with onychomycosis that developed a skin rash during treatment with a generic formulation of itraconazole. Drug administration and its re...

Generic medicine and prescribing: A quick assessment

Directory of Open Access Journals (Sweden)

Mainul Haque

2017-01-01

Full Text Available Generic drugs are copies of brand-name drugs that have exactly the same dosage, intended use, effects, side effects, route of administration, risks, safety, and strength as the original drug. In other words, their pharmacological effects are exactly the same as those of their brand-name counterparts. The Food and Drug Administration (FDA describes that generic drugs are essential possibilities that allow better access to healthcare for all Americans. They are replicas of brand-name drugs and are the identical as those of brand-name drugs in dosage form, safety, strength, route of administration, quality, performance features, and anticipated to use. Healthcare authorities and users can be guaranteed that FDA-approved generic drug products have met the same stiff principles as the innovator drug. The company that made Bayer aspirin fought in court enthusiastically to keep generic versions off the shelves, in the 1920s. The company lost in court, and consumers suddenly had an array of choices in generic aspirin. The Supreme Court of India uttering ‘the Supreme Court's ruling will prevent companies from further seeking unwarranted patents on HIV and other essential medicines.’ Generic medicine cannot be sold at a price higher than the branded medicine, so it is regularly a low-priced option. Thereafter, both the end user and the government who pay for part of the price of the medicine under the Pharmaceutical Benefits Scheme in Australia are benefitted. The treatment of diseases using essential drugs, prescribed by their generic names, has been emphasised by the WHO and many national health policies. Although there are some improvements in generic medicine prescribing, it has been advised by the WHO that ‘countries should intensify efforts to measure and regularly monitor medicine prices and availability, and adopt policy measures to address the issues identified.’

Mesoderm Lineage 3D Tissue Constructs Are Produced at Large-Scale in a 3D Stem Cell Bioprocess.

Science.gov (United States)

Cha, Jae Min; Mantalaris, Athanasios; Jung, Sunyoung; Ji, Yurim; Bang, Oh Young; Bae, Hojae

2017-09-01

Various studies have presented different approaches to direct pluripotent stem cell differentiation such as applying defined sets of exogenous biochemical signals and genetic/epigenetic modifications. Although differentiation to target lineages can be successfully regulated, such conventional methods are often complicated, laborious, and not cost-effective to be employed to the large-scale production of 3D stem cell-based tissue constructs. A 3D-culture platform that could realize the large-scale production of mesoderm lineage tissue constructs from embryonic stem cells (ESCs) is developed. ESCs are cultured using our previously established 3D-bioprocess platform which is amenable to mass-production of 3D ESC-based tissue constructs. Hepatocarcinoma cell line conditioned medium is introduced to the large-scale 3D culture to provide a specific biomolecular microenvironment to mimic in vivo mesoderm formation process. After 5 days of spontaneous differentiation period, the resulting 3D tissue constructs are composed of multipotent mesodermal progenitor cells verified by gene and molecular expression profiles. Subsequently the optimal time points to trigger terminal differentiation towards cardiomyogenesis or osteogenesis from the mesodermal tissue constructs is found. A simple and affordable 3D ESC-bioprocess that can reach the scalable production of mesoderm origin tissues with significantly improved correspondent tissue properties is demonstrated. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

40 CFR 721.5350 - Substituted nitrile (generic name).

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted nitrile (generic name... Substances § 721.5350 Substituted nitrile (generic name). (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified generically as a substituted nitrile (PMN P-83...

Generic Penetration of the SSRI Market.

Science.gov (United States)

Cascade, Elisa F; Kalali, Amir H

2008-04-01

In this article, we investigate the penetration of generic selective serotonin reuptake inhibitors (SSRIs) in the US market and the implications for patient out-of-pocket expense. The data suggest that generic penetration into the SSRI market has grown from approximately nine percent in 2000, the year that the patent for Prozac((R)) expired, to 72 percent in 2007. For December, 2007, the difference in patient out-of-pocket expense for branded vs. generic agents was, on average, $55.42 for patients paying by cash (i.e., they had no prescription drug insurance) and $22.39 for patients with insurance coverage.

Consolidated bioprocessing for production of polyhydroxyalkanotes from red algae Gelidium amansii.

Science.gov (United States)

Sawant, Shailesh S; Salunke, Bipinchandra K; Kim, Beom Soo

2018-04-01

Noncompetitive carbon sources such as algae are unconventional and promising raw material for sustainable biofuel production. The capability of one marine bacterium, Saccharophagus degradans 2-40 to degrade red seaweed Gelidium amansii for production of polyhydroxyalkanoates (PHA) was evaluated in this study. S. degradans can readily attach to algae, degrade algal carbohydrates, and utilize that material as main carbon source. Minimal media containing 8g/L G. amansii were used for the growth of S. degradans. The PHA content obtained was 17-27% of dry cell weight by pure culture of S. degradans and co-culture of S. degradans and Bacillus cereus, a contaminant found with S. degradans cultures. The PHA type was found to be poly(3-hydroxybutyrate) by gas chromatography and Fourier transform-infrared spectroscopy. This work demonstrates PHA production through consolidated bioprocessing of insoluble, untreated red algae by bacterial pure culture and co-culture. Copyright © 2017 Elsevier B.V. All rights reserved.

Bioprocess systems engineering: transferring traditional process engineering principles to industrial biotechnology.

Science.gov (United States)

Koutinas, Michalis; Kiparissides, Alexandros; Pistikopoulos, Efstratios N; Mantalaris, Athanasios

2012-01-01

The complexity of the regulatory network and the interactions that occur in the intracellular environment of microorganisms highlight the importance in developing tractable mechanistic models of cellular functions and systematic approaches for modelling biological systems. To this end, the existing process systems engineering approaches can serve as a vehicle for understanding, integrating and designing biological systems and processes. Here, we review the application of a holistic approach for the development of mathematical models of biological systems, from the initial conception of the model to its final application in model-based control and optimisation. We also discuss the use of mechanistic models that account for gene regulation, in an attempt to advance the empirical expressions traditionally used to describe micro-organism growth kinetics, and we highlight current and future challenges in mathematical biology. The modelling research framework discussed herein could prove beneficial for the design of optimal bioprocesses, employing rational and feasible approaches towards the efficient production of chemicals and pharmaceuticals.

Bioprocess systems engineering: transferring traditional process engineering principles to industrial biotechnology

Directory of Open Access Journals (Sweden)

Michalis Koutinas

2012-10-01

Full Text Available The complexity of the regulatory network and the interactions that occur in the intracellular environment of microorganisms highlight the importance in developing tractable mechanistic models of cellular functions and systematic approaches for modelling biological systems. To this end, the existing process systems engineering approaches can serve as a vehicle for understanding, integrating and designing biological systems and processes. Here, we review the application of a holistic approach for the development of mathematical models of biological systems, from the initial conception of the model to its final application in model-based control & optimisation. We also discuss the use of mechanistic models that account for gene regulation, in an attempt to advance the empirical expressions traditionally used to describe micro-organism growth kinetics, and we highlight current and future challenges in mathematical biology. The modelling research framework discussed herein could prove beneficial for the design of optimal bioprocesses, employing rational and feasible approaches towards the efficient production of chemicals and pharmaceuticals.

BIOPROCESS SYSTEMS ENGINEERING: TRANSFERRING TRADITIONAL PROCESS ENGINEERING PRINCIPLES TO INDUSTRIAL BIOTECHNOLOGY

Directory of Open Access Journals (Sweden)

Michalis Koutinas

2012-10-01

Full Text Available The complexity of the regulatory network and the interactions that occur in the intracellular environment of microorganisms highlight the importance in developing tractable mechanistic models of cellular functions and systematic approaches for modelling biological systems. To this end, the existing process systems engineering approaches can serve as a vehicle for understanding, integrating and designing biological systems and processes. Here, we review the application of a holistic approach for the development of mathematical models of biological systems, from the initial conception of the model to its final application in model-based control and optimisation. We also discuss the use of mechanistic models that account for gene regulation, in an attempt to advance the empirical expressions traditionally used to describe micro-organism growth kinetics, and we highlight current and future challenges in mathematical biology. The modelling research framework discussed herein could prove beneficial for the design of optimal bioprocesses, employing rational and feasible approaches towards the efficient production of chemicals and pharmaceuticals.

40 CFR 721.555 - Alkyl amino nitriles (generic).

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkyl amino nitriles (generic). 721... Substances § 721.555 Alkyl amino nitriles (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as alkyl amino nitriles (PMNs P-96...

Postprandial glucose metabolism and SCFA after consuming wholegrain rye bread and wheat bread enriched with bioprocessed rye bran in individuals with mild gastrointestinal symptoms

DEFF Research Database (Denmark)

Lappi, J; Mykkänen, H; Knudsen, Knud Erik Bach

2014-01-01

BackgroundRye bread benefits glucose metabolism. It is unknown whether the same effect is achieved by rye bran-enriched wheat bread. We tested whether white wheat bread enriched with bioprocessed rye bran (BRB + WW) and sourdough wholegrain rye bread (WGR) have similar effects on glucose metabolism...... and plasma level of short chain fatty acids (SCFAs).  MethodsTwenty-one (12 women) of 23 recruited subjects completed an intervention with a four-week run-in and two four-week test periods in cross-over design. White wheat bread (WW; 3% fibre) was consumed during the run-in, and WGR and BRB + WW (10% fibre.......05) and propionate (p = 0.009) at 30 min increased during both rye bread periods.ConclusionsBeneficial effects of WGR over white wheat bread on glucose and SCFA production were confirmed. The enrichment of the white wheat bread with bioprocessed rye bran (BRB + WW) yielded similar but not as pronounced effects than...

A Generic Approach to Parameter Control

NARCIS (Netherlands)

Karafotias, G.; Smit, S.K.; Eiben, A.E.

2012-01-01

On-line control of EA parameters is an approach to parameter setting that offers the advantage of values changing during the run. In this paper, we investigate parameter control from a generic and parameter-independent perspective. We propose a generic control mechanism that is targeted to

Developing competitive and sustainable Polish generic medicines market.

Science.gov (United States)

Simoens, Steven

2009-10-01

To descriptively analyze the policy environment surrounding the Polish generic medicines retail market. The policy analysis was based on an international literature review. Also, a simulation exercise was carried out to compute potential savings from substituting generic for originator medicines in Poland using IMS Health pharmaceutical intelligence data. Poland has a mature, high-volume, low-value generic medicines market, primarily driven by the establishment of the reference price at the price of the cheapest medicine in combination with pricing regulation and the low level of medicine prices. The practice of discounting in the distribution chain implies that the National Health Fund and patients do not capture the potential savings from a generic medicines market where companies compete on price. This high-volume market has benefited in the past from the limited availability of originator medicines and a short data exclusivity period, even though there are no incentives for physicians to prescribe generic medicines and a financial disincentive for pharmacists to dispense generic medicines. Increased generic substitution would be expected to reduce public expenditure on originator medicines by 21%. To develop a competitive and sustainable market, Poland needs to consider moving away from competition by discount to competition by price. This could be achieved by replacing maximum distribution margins by fixed margins. Also, Poland may wish to raise reference prices as a temporary measure to boost market entry for medicine classes with few generic medicines.

The Generic Data Capture Facility

Science.gov (United States)

Connell, Edward B.; Barnes, William P.; Stallings, William H.

1987-01-01

The Generic Data Capture Facility, which can provide data capture support for a variety of different types of spacecraft while enabling operations costs to be carefully controlled, is discussed. The data capture functions, data protection, isolation of users from data acquisition problems, data reconstruction, and quality and accounting are addressed. The TDM and packet data formats utilized by the system are described, and the development of generic facilities is considered.

Does educational intervention improve doctors’ knowledge and perceptions of generic medicines and their generic prescribing rate? A study from Malaysia

Science.gov (United States)

Wong, Zhi Yen; Alrasheedy, Alian A.; Saleem, Fahad; Mohamad Yahaya, Abdul Haniff; Aljadhey, Hisham

2014-01-01

Objectives: To investigate the impact of an educational intervention on doctors’ knowledge and perceptions towards generic medicines and their generic (international non-proprietary name) prescribing practice. Methods: This is a single-cohort pre-/post-intervention pilot study. The study was conducted in a tertiary care hospital in Perak, Malaysia. All doctors from the internal medicine department were invited to participate in the educational intervention. The intervention consisted of an interactive lecture, an educational booklet and a drug list. Doctors’ knowledge and perceptions were assessed by using a validated questionnaire, while the international non-proprietary name prescribing practice was assessed by screening the prescription before and after the intervention. Results: The intervention was effective in improving doctors’ knowledge towards bioequivalence, similarity of generic medicines and safety standards required for generic medicine registration (p = 0.034, p = 0.034 and p = 0.022, respectively). In terms of perceptions towards generic medicines, no significant changes were noted (p > 0.05). Similarly, no impact on international non-proprietary name prescribing practice was observed after the intervention (p > 0.05). Conclusion: Doctors had inadequate knowledge and misconceptions about generic medicines before the intervention. Moreover, international non-proprietary name prescribing was not a common practice. However, the educational intervention was only effective in improving doctors’ knowledge of generic medicines. PMID:26770747

A developmental analysis of generic nouns in Southern Peruvian Quechua.

Science.gov (United States)

Mannheim, Bruce; Gelman, Susan A; Escalante, Carmen; Huayhua, Margarita; Puma, Rosalía

2010-01-01

Generic noun phrases (e.g., "Cats like to drink milk") are a primary means by which adults express generalizations to children, yet they pose a challenging induction puzzle for learners. Although prior research has established that English speakers understand and produce generic noun phrases by preschool age, little is known regarding the cross-cultural generality of generic acquisition. Southern Peruvian Quechua provides a valuable comparison because, unlike English, it is a highly inflected language in which generics are marked by the absence rather than the presence of any linguistic markers. Moreover, Quechua is spoken in a cultural context that differs markedly from the highly educated, middle-class contexts within which earlier research on generics was conducted. We presented participants from 5 age groups (3-6, 7-9, 10-12, 14-35, and 36-90 years of age) with two tasks that examined the ability to distinguish generic from non-generic utterances. In Study 1, even the youngest children understood generics as applying broadly to a category (like "all") and distinct from indefinite reference ("some"). However, there was a developmental lag before children understood that generics, unlike "all", can include exceptions. Study 2 revealed that generic interpretations are more frequent for utterances that (a) lack specifying markers and (b) are animate. Altogether, generic interpretations are found among the youngest participants, and may be a default mode of quantification. These data demonstrate the cross-cultural importance of generic information in linguistic expression.

Associations between generic substitution and patient-related factors

DEFF Research Database (Denmark)

Østergaard Rathe, Jette

Associations between generic substitution and patient-related factors Jette Østergaard Rathe1, Pia V. Larsen1, Morten Andersen2, Janus L. Thomsen3, Maja S. Paulsen1, Jens Søndergaard1 1. Research Unit of General Practice, Institute of Public Health, University of Southern Denmark 2. Centre...... for Pharmacoepidemiology, Karolinska Institutet, Department of Medicine Solna, Stockholm, Sweden 3. Danish Quality Unit of General Practice, Odense, Denmark Background Generic substitution means that chemically equivalent but less expensive drugs are dispensed in place of a brand name product. Although generic medicines...... by definition are bioequivalent to their brand name counterparts there are concerns about whether generic substitution is always accompanied by clinical equivalence in terms of effectiveness and that it may cause concerns and thereby causing some skepticism towards generic substitution. There is, however...

Commercial viability of CNS drugs: balancing the risk/reward profile.

Science.gov (United States)

Johnson, Ginger S

2014-01-01

CNS has historically been a formidable therapeutic area in which to innovate owing to biological (e.g., complex neurobiology, difficulty reaching the target), as well as clinical (e.g., subjective clinical endpoints, high placebo response, lack of biomarkers) challenges. In the current market where many of the larger diseases are dominated by a generic standard of care, commercial challenges now make the triple threat of scientific-clinical-commercial risk too much for many players to tackle. However, opportunities do exist for smaller biotech companies to concentrate on narrowly focused patient populations associated with high unmet need for which risk can be tightly defined. In CNS, there are two major areas to balance the risk/reward profile and create commercially viable opportunities: To realize value, all companies (start-ups and big players) must define, measure and quantify clear and meaningful value to all stakeholders: physicians, patients, caregivers and payers. © 2013.

Consumer choice between common generic and brand medicines in a country with a small generic market.

Science.gov (United States)

Fraeyman, Jessica; Peeters, Lies; Van Hal, Guido; Beutels, Philippe; De Meyer, Guido R Y; De Loof, Hans

2015-04-01

Generic medicines offer an opportunity for governments to contain pharmaceutical expenditures, since generics are generally 10%-80% lower in price than brand medicines. Belgium has a small generic market that takes up 15% of the total pharmaceutical market in packages sold. To determine the knowledge of consumers about the different available packages of a common over-the-counter medicine (acetaminophen) with regard to price advantage, quality, and effectiveness in a country with a small generic market. We conducted an online survey in the general Flemish population using a questionnaire with 25 statements. The questionnaire also contained 2 informative interventions. First, we showed the price per package and per tablet that the patient would pay in the pharmacy. Second, we provided the respondent with general information about generic medication (equivalence, effectiveness, price, and recognition). Before and after the interventions, we probed for preferences and knowledge about the different packages. Multivariate logistic models were used to examine the independent effects of consumer characteristics on responses to the survey statements. We obtained a sample of 1,636 respondents. The general attitude towards generic medication was positive-only 5% would rather not use a generic. Nevertheless, only 17% of the respondents were able to recognize a generic medicine. Older consumers (aged 60 years and above) were more often confused about the different packages (OR = 2.59, 95% CI = 1.76-3.80, P ≤ 0.001). Consumers without a higher education degree tended to be more doubtful about the difference in effectiveness and quality between the different brands (OR = 0.59, 95% CI = 0.44-0.79, P ≤ 0.001). Consumer recognition of the name of the active substance of acetaminophen was poor. When different brands were displayed, possible price advantage seemed to be an important motive to switch to a cheaper brand. Consumers generally found medicines

Human pluripotent stem cell-derived products: advances towards robust, scalable and cost-effective manufacturing strategies.

Science.gov (United States)

Jenkins, Michael J; Farid, Suzanne S

2015-01-01

The ability to develop cost-effective, scalable and robust bioprocesses for human pluripotent stem cells (hPSCs) will be key to their commercial success as cell therapies and tools for use in drug screening and disease modelling studies. This review outlines key process economic drivers for hPSCs and progress made on improving the economic and operational feasibility of hPSC bioprocesses. Factors influencing key cost metrics, namely capital investment and cost of goods, for hPSCs are discussed. Step efficiencies particularly for differentiation, media requirements and technology choice are amongst the key process economic drivers identified for hPSCs. Progress made to address these cost drivers in hPSC bioprocessing strategies is discussed. These include improving expansion and differentiation yields in planar and bioreactor technologies, the development of xeno-free media and microcarrier coatings, identification of optimal bioprocess operating conditions to control cell fate and the development of directed differentiation protocols that reduce reliance on expensive morphogens such as growth factors and small molecules. These approaches offer methods to further optimise hPSC bioprocessing in terms of its commercial feasibility. © 2014 The Authors. Biotechnology Journal published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Family Genericity

DEFF Research Database (Denmark)

Ernst, Erik

2006-01-01

Type abstraction in object-oriented languages embody two techniques, each with its own strenghts and weaknesses. The first technique is extension, yielding abstraction mechanisms with good support for gradual specification. The prime example is inheritance. The second technique is functional abst...... the result as family genericity. The presented language design has been implemented....

Hanford Generic Interim Safety Basis

International Nuclear Information System (INIS)

Lavender, J.C.

1994-01-01

The purpose of this document is to identify WHC programs and requirements that are an integral part of the authorization basis for nuclear facilities that are generic to all WHC-managed facilities. The purpose of these programs is to implement the DOE Orders, as WHC becomes contractually obligated to implement them. The Hanford Generic ISB focuses on the institutional controls and safety requirements identified in DOE Order 5480.23, Nuclear Safety Analysis Reports

Hanford Generic Interim Safety Basis

Energy Technology Data Exchange (ETDEWEB)

Lavender, J.C.

1994-09-09

The purpose of this document is to identify WHC programs and requirements that are an integral part of the authorization basis for nuclear facilities that are generic to all WHC-managed facilities. The purpose of these programs is to implement the DOE Orders, as WHC becomes contractually obligated to implement them. The Hanford Generic ISB focuses on the institutional controls and safety requirements identified in DOE Order 5480.23, Nuclear Safety Analysis Reports.

Advances on generic exemption levels and generic clearance levels in the argentinean regulatory field

International Nuclear Information System (INIS)

Muñiz, C.C.; Bossio, M.C.

2011-01-01

With the aim of optimizing the regulatory effort in Argentina, the Nuclear Regulatory Authority (ARN) evaluated two worldwide concepts used in the radioactive waste management field: “Generic Exemption Levels” and “Generic Clearance Levels”. The objective of this paper is to present the progress made in the past two years in relation to these topics and to present the results of the specific requests received from users of radioactive material. Since the approval of both Generic Levels, the ARN received two exemption requests. The first one, regarding the practice of dismantling lighting rods with 241 Am. The other case regards the international trade, distribution, usage and final disposal of lighting products with radioactive material ( 85 Kr and 232 Th). Concerning clearance, there has not been any request yet. However, in the future the ARN expects to receive this kind of requests from nuclear power plants and other facilities related to the nuclear fuel cycle. (authors) [es

Generic medications for you, but brand-name medications for me.

Science.gov (United States)

Keenum, Amy J; Devoe, Jennifer E; Chisolm, Deena J; Wallace, Lorraine S

2012-01-01

Because generic medications are less expensive than brand-name medications, government and private insurers have encouraged and/or mandated the use of generics. This study aimed at evaluating perceptions about generic medications among English-speaking women of childbearing age currently enrolled in U.S. TennCare (Medicaid). We recruited a convenience sample of patients from the waiting room of a primary care/gynecology health clinic, with 80% recruitment rate among those approached. We orally administered a 25-item questionnaire to gather sociodemographic information and to assess beliefs regarding the efficacy, safety, cost, and preferences for personal use of generic medications. The average age of the women (n=172) was 28.8 ± 6.4 years, and most were white (82.0%) and currently married (58.1%). Nearly one-fifth (19.2%) had not completed high school. Most women believed that generic medications were less expensive (97.6%) and better value (60.5%) than brand-name medications, but only 45.3% preferred to take generics themselves. About a quarter (23.3%) believed that brand-name medications were more effective than generics, whereas 13.4% believed that generics caused more side effects. Few women reported that their doctor (29.7%) and/or pharmacist (35.5%) had ever talked to them about taking generics. Awareness of the benefits of generics did not equal preferences for personal use of generics among this sample of women enrolled in U.S. TennCare. Furthermore, women reported that providers-both physicians and pharmacists-infrequently discussed generic substitution with them. Copyright © 2012 Elsevier Inc. All rights reserved.

Towards Using a Generic Robot as Training Partner

DEFF Research Database (Denmark)

Sørensen, Anders Stengaard; Savarimuthu, Thiusius Rajeeth; Nielsen, Jacob

2014-01-01

In this paper, we demonstrate how a generic industrial robot can be used as a training partner, for upper limb training. The motion path and human/robot interaction of a non-generic upper-arm training robot is transferred to a generic industrial robot arm, and we demonstrate that the robot arm can...... implement the same type of interaction, but can expand the training regime to include both upper arm and shoulder training. We compare the generic robot to two affordable but custom-built training robots, and outline interesting directions for future work based on these training robots....

Innovation strategies for generic drug companies: moving into supergenerics.

Science.gov (United States)

Ross, Malcolm S F

2010-04-01

Pharmaceutical companies that market generic products generally are not regarded as innovators, but rather as companies that produce copies of originator products to be launched at patent expiration. However, many generics companies have developed excellent scientific innovative skills in an effort to circumvent the defense patents of originator companies. More patents per product, in terms of both drug substances (process patents and polymorph patents) and formulations, are issued to generics companies than to companies that are traditionally considered to be 'innovators'. This quantity of issued patents highlights the technical knowledge and skill sets that are available in generics companies. In order to adopt a completely innovative model (ie, the development of NCEs), a generics company would require a completely new set of skills in several fields, including a sufficient knowledge base, project and risk management experience, and capability for clinical data evaluation. However, with relatively little investment, generics companies should be able to progress into the so-called 'supergeneric' drug space - an area of innovation that reflects the existing competencies of both innovative and generics companies.

78 FR 22553 - Generic Drug Facilities, Sites, and Organizations

Science.gov (United States)

2013-04-16

...] Generic Drug Facilities, Sites, and Organizations AGENCY: Food and Drug Administration, HHS. ACTION.... Generic drug facilities, certain sites, and organizations identified in a generic drug submission are... active pharmaceutical ingredients and certain other sites and organizations that support the manufacture...

STS-69 flight day 6 highlights

Science.gov (United States)

1995-09-01

After being awakened by the Beatles song, 'A Hard Days Night', the flightcrew of the STS-69 mission, Cmdr. Dave Walker, Pilot Ken Cockrell, and Mission Specialists Jim Voss, Jim Newman, and Mike Gernhardt, began their sixth day in orbit by monitoring the free orbiting Wake Shield Facility (WSF). Later Cmdr. Walker conducted an interview with television reporters from Atlanta and Boston, answering questions about the mission and general questions about NASA's space program. The crew filmed a video fo themselves performing daily routines (eating, shaving, exercising), as well as some of the physiological experiments, and shuttle equipment maintenance and checkout. One of the secondary experiments included the Commercial Generic Bioprocessing Apparatus-7 (CGBA-7), which served as an incubator and experiment station for a variety of tests (agricultural, pharmaceutical, biomedical, and environmental). Earth views included some cloud cover, the Gulf of Mexico, Texas, and the Atlantic Ocean.

Integration of generic issues

International Nuclear Information System (INIS)

Thatcher, D.

1989-01-01

The NRC has recognized the need to integrate generic issues (GIs). The GI process includes a number of phases, all of which should recognize the potential for overlap and conflict among related issues. In addition to the issues themselves, other related NRC and industry programs and activities need to be factored into the GI process. Integration has taken place, or is taking place, for a number of GIs. Each case of integration involves a specific set of circumstances and, as a result, the way in which integration proceeds can vary. This paper discusses the integration of issues in the generic issue process and provides a number of examples

Development of a new bioprocess scheme using frozen seed train intermediates to initiate CHO cell culture manufacturing campaigns.

Science.gov (United States)

Seth, Gargi; Hamilton, Robert W; Stapp, Thomas R; Zheng, Lisa; Meier, Angela; Petty, Krista; Leung, Stephenie; Chary, Srikanth

2013-05-01

Agility to schedule and execute cell culture manufacturing campaigns quickly in a multi-product facility will play a key role in meeting the growing demand for therapeutic proteins. In an effort to shorten campaign timelines, maximize plant flexibility and resource utilization, we investigated the initiation of cell culture manufacturing campaigns using CHO cells cryopreserved in large volume bags in place of the seed train process flows that are conventionally used in cell culture manufacturing. This approach, termed FASTEC (Frozen Accelerated Seed Train for Execution of a Campaign), involves cultivating cells to high density in a perfusion bioreactor, and cryopreserving cells in multiple disposable bags. Each run for a manufacturing campaign would then come from a thaw of one or more of these cryopreserved bags. This article reviews the development and optimization of individual steps of the FASTEC bioprocess scheme: scaling up cells to greater than 70 × 10(6) cells/mL and freezing in bags with an optimized controlled rate freezing protocol and using a customized rack configuration. Flow cytometry analysis was also employed to understand the recovery of CHO cells following cryopreservation. Extensive development data were gathered to ensure that the quantity and quality of the drug manufactured using the FASTEC bioprocess scheme was acceptable compared to the conventional seed train process flow. The result of offering comparable manufacturing options offers flexibility to the cell culture manufacturing network. Copyright © 2012 Wiley Periodicals, Inc.

South African patient's acceptance of generic drugs

African Journals Online (AJOL)

mechanism in this regard for final consumers, insurance providers, and ... facilities are viewed as inferior, treated with sus- picion and ... to choose a generic drug if the decision was supported by their doctor ... The effect of brand to generic and ...

Impact of generic substitution decision support on electronic prescribing behavior.

Science.gov (United States)

Stenner, Shane P; Chen, Qingxia; Johnson, Kevin B

2010-01-01

To evaluate the impact of generic substitution decision support on electronic (e-) prescribing of generic medications. The authors analyzed retrospective outpatient e-prescribing data from an academic medical center and affiliated network for July 1, 2005-September 30, 2008 using an interrupted time-series design to assess the rate of generic prescribing before and after implementing generic substitution decision support. To assess background secular trends, e-prescribing was compared with a concurrent random sample of hand-generated prescriptions. Proportion of generic medications prescribed before and after the intervention, evaluated over time, and compared with a sample of prescriptions generated without e-prescribing. The proportion of generic medication prescriptions increased from 32.1% to 54.2% after the intervention (22.1% increase, 95% CI 21.9% to 22.3%), with no diminution in magnitude of improvement post-intervention. In the concurrent control group, increases in proportion of generic prescriptions (29.3% to 31.4% to 37.4% in the pre-intervention, post-intervention, and end-of-study periods, respectively) were not commensurate with the intervention. There was a larger change in generic prescribing rates among authorized prescribers (24.6%) than nurses (18.5%; adjusted OR 1.38, 95% CI 1.17 to 1.63). Two years after the intervention, the proportion of generic prescribing remained significantly higher for e-prescriptions (58.1%; 95% CI 57.5% to 58.7%) than for hand-generated prescriptions ordered at the same time (37.4%; 95% CI 34.9% to 39.9%) (p<0.0001). Generic prescribing increased significantly in every specialty. Implementation of generic substitution decision support was associated with dramatic and sustained improvements in the rate of outpatient generic e-prescribing across all specialties.

Bioprocessing of lignite coals using reductive microorganisms. Final technical report, September 30, 1988--March 29, 1992

Energy Technology Data Exchange (ETDEWEB)

Crawford, D.L.

1992-03-29

In order to convert lignite coals into liquid fuels, gases or chemical feedstock, the macromolecular structure of the coal must be broken down into low molecular weight fractions prior to further modification. Our research focused on this aspect of coal bioprocessing. We isolated, characterized and studied the lignite coal-depolymerizing organisms Streptomyces viridosporus T7A, Pseudomonas sp. DLC-62, unidentified bacterial strain DLC-BB2 and Gram-positive Bacillus megaterium strain DLC-21. In this research we showed that these bacteria are able to solubilize and depolymerize lignite coals using a combination of biological mechanisms including the excretion of coal solublizing basic chemical metabolites and extracellular coal depolymerizing enzymes.

Generic Graph Grammar: A Simple Grammar for Generic Procedural Modelling

DEFF Research Database (Denmark)

Christiansen, Asger Nyman; Bærentzen, Jakob Andreas

2012-01-01

in a directed cyclic graph. Furthermore, the basic productions are chosen such that Generic Graph Grammar seamlessly combines the capabilities of L-systems to imitate biological growth (to model trees, animals, etc.) and those of split grammars to design structured objects (chairs, houses, etc.). This results...

The importance of being first: evidence from Canadian generic pharmaceuticals.

Science.gov (United States)

Hollis, Aidan

2002-12-01

This paper uses pooled cross-section data on Canadian ethical drug sales to examine the effect of entry timing on sales of generic drugs. The data is for all drugs for which the first generic competitor entered during the years 1994-1997. It is found that the first generic entrant has a lasting competitive advantage: being first into the market appears to lead to an increase of around 30% in market share (among generics) over a period of at least 4 years. This finding has considerable implications for the current policy of allowing brandname drug companies to issue pseudo-generic equivalents as a preemptive strike against true generic competitors. Copyright 2002 John Wiley & Sons, Ltd.

Generic substitution of antiretrovirals: patients' and health care providers' opinions.

Science.gov (United States)

Kieran, Jennifer A; O'Reilly, Eimear; O'Dea, Siobhan; Bergin, Colm; O'Leary, Aisling

2017-10-01

There is interest in introducing generic antiretroviral drugs (ARVs) into high-income countries in order to maximise efficiency in health care budgets. Studies examining patients' and providers' knowledge and attitudes to generic substitution in HIV are few. This was a cross-sectional, observational study with a convenience sample of adult HIV-infected patients and health care providers (HCPs). Data on demographics, knowledge of generic medicine and facilitators of generic substitution were collected. Descriptive and univariate analysis was performed using SPSS V.23™. Questionnaires were completed by 66 patients. Seventy-one per cent would have no concerns with the introduction of generic ARVs. An increase in frequency of administration (61%) or pill burden (53%) would make patients less likely to accept generic ARVs. There were 30 respondents to the HCP survey. Concerns included the supply chain of generics, loss of fixed dose combinations, adherence and use of older medications. An increase in dosing frequency (76%) or an increase in pill burden (50%) would make HCPs less likely to prescribe a generic ARV. The main perceived advantage was financial. Generic substitution of ARVs would be acceptable to the majority of patients and HCPs. Reinvesting savings back into HIV services would facilitate the success of such a programme.

Development and application of an excitation ratiometric optical pH sensor for bioprocess monitoring.

Science.gov (United States)

Badugu, Ramachandram; Kostov, Yordan; Rao, Govind; Tolosa, Leah

2008-01-01

The development of a fluorescent excitation ratiometric pH sensor (AHQ-PEG) using a novel allylhydroxyquinolinium (AHQ) derivative copolymerized with polyethylene glycol dimethacrylate (PEG) is described. The AHQ-PEG sensor film is shown to be suitable for real-time, noninvasive, continuous, online pH monitoring of bioprocesses. Optical ratiometric measurements are generally more reliable, robust, inexpensive, and insensitive to experimental errors such as fluctuations in the source intensity and fluorophore photobleaching. The sensor AHQ-PEG in deionized water was shown to exhibit two excitation maxima at 375 and 425 nm with a single emission peak at 520 nm. Excitation spectra of AHQ-PEG show a decrease in emission at the 360 nm excitation and an increase at the 420 nm excitation with increasing pH. Accordingly, the ratio of emission at 420:360 nm excitation showed a maximum change between pH 5 and 8 with an apparent pK(a) of 6.40. The low pK(a) value is suitable for monitoring the fermentation of most industrially important microorganisms. Additionally, the AHQ-PEG sensor was shown to have minimal sensitivity to ionic strength and temperature. Because AHQ is covalently attached to PEG, the film shows no probe leaching and is sterilizable by steam and alcohol. It shows rapid (approximately 2 min) and reversible response to pH over many cycles without any photobleaching. Subsequently, the AHQ-PEG sensor film was tested for its suitability in monitoring the pH of S. cereviseae (yeast) fermentation. The observed pH using AHQ-PEG film is in agreement with a conventional glass pH electrode. However, unlike the glass electrode, the present sensor is easily adaptable to noninvasive monitoring of sterilized, closed bioprocess environments without the awkward wire connections that electrodes require. In addition, the AHQ-PEG sensor is easily miniaturized to fit in microwell plates and microbioreactors for high-throughput cell culture applications.

Methodological Considerations for Comparison of Brand Versus Generic Versus Authorized Generic Adverse Event Reports in the US Food and Drug Administration Adverse Event Reporting System (FAERS).

Science.gov (United States)

Rahman, Md Motiur; Alatawi, Yasser; Cheng, Ning; Qian, Jingjing; Peissig, Peggy L; Berg, Richard L; Page, David C; Hansen, Richard A

2017-12-01

The US Food and Drug Administration Adverse Event Reporting System (FAERS), a post-marketing safety database, can be used to differentiate brand versus generic safety signals. To explore the methods for identifying and analyzing brand versus generic adverse event (AE) reports. Public release FAERS data from January 2004 to March 2015 were analyzed using alendronate and carbamazepine as examples. Reports were classified as brand, generic, and authorized generic (AG). Disproportionality analyses compared reporting odds ratios (RORs) of selected known labeled serious adverse events stratifying by brand, generic, and AG. The homogeneity of these RORs was compared using the Breslow-Day test. The AG versus generic was the primary focus since the AG is identical to brand but marketed as a generic, therefore minimizing generic perception bias. Sensitivity analyses explored how methodological approach influenced results. Based on 17,521 US event reports involving alendronate and 3733 US event reports involving carbamazepine (immediate and extended release), no consistently significant differences were observed across RORs for the AGs versus generics. Similar results were obtained when comparing reporting patterns over all time and just after generic entry. The most restrictive approach for classifying AE reports yielded smaller report counts but similar results. Differentiation of FAERS reports as brand versus generic requires careful attention to risk of product misclassification, but the relative stability of findings across varying assumptions supports the utility of these approaches for potential signal detection.

Generic implications of the Chernobyl accident

International Nuclear Information System (INIS)

Sege, G.

1989-01-01

The US Nuclear Regulatory Commission (NRC) staff's assessment of the generic implications of the Chernobyl accident led to the conclusion that no immediate changes in the NRC's regulations regarding design or operation of US commercial reactors are needed. However, further consideration of certain issues was recommended. This paper discusses those issues and the studies being addressed to them. Although 24 tasks relating to light water reactor issues are identified in the Chernobyl follow-up research program, only four are new initiatives originating from Chernobyl implications. The remainder are limited modifications of ongoing programs designed to ensure that those programs duly reflect any lessons that may be drawn from the Chernobyl experience. The four new study tasks discussed include a study of reactivity transients, to reconfirm or bring into question the adequacy of potential reactivity accident sequences hitherto selected as a basis for design approvals; analysis of risk at low power and shutdown; a study of procedure violations; and a review of current NRC testing requirements for balance of benefits and risks. Also discussed, briefly, are adjustments to ongoing studies in the areas of operational controls, design, containment, emergency planning, and severe accident phenomena

Process integration in bioprocess indystry: waste heat recovery in yeast and ethyl alcohol plant

International Nuclear Information System (INIS)

Raskovic, P.; Anastasovski, A.; Markovska, Lj.; Mesko, V.

2010-01-01

The process integration of the bioprocess plant for production of yeast and alcohol was studied. Preliminary energy audit of the plant identified the huge amount of thermal losses, caused by waste heat in exhausted process streams, and reviled the great potential for energy efficiency improvement by heat recovery system. Research roadmap, based on process integration approach, is divided on six phases, and the primary tool used for the design of heat recovery network was Pinch Analysis. Performance of preliminary design are obtained by targeting procedure, for three process stream sets, and evaluated by the economic criteria. The results of process integration study are presented in the form of heat exchanger networks which fulfilled the utilization of waste heat and enable considerable savings of energy in short payback period.

Policies and perceptions on generic drugs: The case of Greece.

Science.gov (United States)

Xanthopoulou, Sofia-Sotiria; Katsaliaki, Korina

2018-01-01

The increase in the consumption of generic drugs to reduce pharmaceutical expenditure is a challenge for many countries, especially during the economic crisis. The purpose of the present study is to review the Greek market of generic drugs and the decisions that shape it, to determine the factors that affect Greek patients' and doctors' attitudes about generic substitution and present a set of measures for all stakeholders based on the findings of the secondary and primary analysis. The study includes (a) an analysis of international and national reports and legislation on drugs policies and (b) a questionnaire survey of 242 hospital patients and 85 doctors regarding their perceptions on generics. A small increase in the volume of generics is recorded, yet not followed by sales value, over the recent years that the measures for promoting generics prescription took effect. Distrust from both patients and doctors was observed toward generics' effectiveness and toward the appropriateness of the regulatory authorities' quality controls. The study presents a structured set of viable measures, applicable to many countries, for promoting generic drug consumption that can lead to economic efficiency without degrading the health care quality.

Encouraging the use of generic medicines: implications for transition economies.

Science.gov (United States)

King, Derek R; Kanavos, Panos

2002-08-01

Generic drugs have a key role to play in the efficient allocation of financial resources for pharmaceutical medicines. Policies implemented in the countries with a high rate of generic drug use, such as Canada, Denmark, Germany, the Netherlands, the United Kingdom, and the United States, are reviewed, with consideration of the market structures that facilitate strong competition. Savings in these countries are realized through increases in the volume of generic drugs used and the frequently significant differences in the price between generic medicines and branded originator medicines. Their policy tools include the mix of supply-side measures and demand-side measures that are relevant for generic promotion and higher generic use. On the supply-side, key policy measures include generic drug marketing regulation that facilitates market entry soon after patent expiration, reference pricing, the pricing of branded originator products, and the degree of price competition in pharmaceutical markets. On the demand-side, measures typically encompass influencing prescribing and dispensing patterns as well as introducing a co-payment structure for consumers/patients that takes into consideration the difference in cost between branded and generic medicines. Quality of generic medicines is a pre-condition for all other measures discussed to take effect. The paper concludes by offering a list of policy options for decision-makers in Central and Eastern European economies in transition.

HTGR generic technology program plan (FY 80)

International Nuclear Information System (INIS)

1980-01-01

Purpose of the program is to develop base technology and to perform design and development common to the HTGR Steam Cycle, Gas Turbine, and Process Heat Plants. The generic technology program breaks into the base technology, generic component, pebble-bed study, technology transfer, and fresh fuel programs

Societal value of generic medicines beyond cost-saving through reduced prices.

Science.gov (United States)

Dylst, Pieter; Vulto, Arnold; Simoens, Steven

2015-01-01

This paper aims to provide an overview of the added societal value of generic medicines beyond their cost-saving potential through reduced prices. In addition, an observational case study will document the impact of generic entry on access to pharmacotherapy in The Netherlands and an illustrative exercise was carried out to highlight the budget impact of generic entry. A narrative literature review was carried out to explore the impact of generic medicines on access to pharmacotherapy, innovation and medication adherence. Data from the Medicines and Medical Devices Information Project database in The Netherlands were used for the case study in which the impact of generic medicine entrance on the budget and the number of users was calculated as an illustrative exercise. Generic medicines have an additional societal value beyond their cost-saving potential through reduced prices. Generic medicines increase access to pharmacotherapy, provide a stimulus for innovation by both originator companies and generic companies and, under the right circumstances, have a positive impact on medication adherence. Generic medicines offer more to society than just their cost-saving potential through reduced prices. As such, governments must not focus only on the prices of generic medicines as this will threaten their long-term sustainability. Governments must therefore act appropriately and implement a coherent set of policies to increase the use of generic medicines.

Generic switching of warfarin and risk of excessive anticoagulation

DEFF Research Database (Denmark)

Hellfritzsch, Maja; Rathe, Jette; Stage, Tore Bjerregaard

2016-01-01

PURPOSE: Generic switching of warfarin was recently repealed in Denmark, as adverse drug reaction (ADR) reports suggested risk of excessive anticoagulation following switches from branded to generic warfarin. We investigated this putative association in a formalized pharmacoepidemiological analysis....... METHODS: We conducted a nationwide cohort study based on Danish healthcare registries, including data from the introduction of generic warfarin until the repeal (January 2011-April 2015). We followed Danish warfarin users over time and compared the rate of incident hospitalizations due to excessive...... anticoagulation (i.e. increased INR or any bleeding requiring hospitalization) in periods following a recent switch to generic warfarin to the rate in periods without a recent switch. RESULTS: We included 105,751 warfarin users, filling a total of 1,539,640 prescriptions for warfarin (2.5% for generic warfarin...

Generic communications index. Listings of communications 1971-1989

Energy Technology Data Exchange (ETDEWEB)

Hagemeyer, D; Towle, H

1991-05-01

As part of its program to feed back information on operating experience to industry, the U.S. Nuclear Regulatory Commission (NRC) issues generic communications called bulletins (about 5/yr), circulars (now discontinued), generic letters (about 20/yr), and information notices (about 100/yr). The report presents an updated Generic Communications Index (GCI; previously published in NUREG/CR-4690, Vol. 1, December 1987) of all such communications from 1971, when such documentation started, to 1989. The GCI consists of records, one for each communication, containing fields for identification number, title, NRC technical contact, general system or topic, specific component or topic, cause or defect, potential effect, remarks, and vendors involved. To facilitate information retrieval, the report also contains topical listings of generic communications numbers. (author)

A generic model for glucose production from various cellulose sources by a commercial cellulase complex

NARCIS (Netherlands)

Drissen, R.E.T.; Maas, R.H.W.; Maarel, M.J.E.C. van der; Kabel, M.A.; Schols, H.A.; Tramper, J.; Beeftink, H.H.

2007-01-01

The kinetics of cellulose hydrolysis by commercially available Cellubrix were described mathematically, with Avicel and wheat straw as substrates. It was demonstrated that hydrolysis could be described by three reactions: direct glucose formation and indirect glucose formation via cellobiose.

The short-term impact of Ontario's generic pricing reforms.

Directory of Open Access Journals (Sweden)

Michael R Law

Full Text Available Canadians pay amongst the highest generic drug prices in the world. In July 2010, the province of Ontario enacted a policy that halved reimbursement for generic drugs from the public drug plan, and substantially lowered prices for private purchases. We quantified the impact of this policy on overall generic drug expenditures in the province, and projected the impact in other provinces had they mimicked this pricing change.We used quarterly prescription generic drug dispensing data from the IMS-Brogan CompuScript Audit. We used the price per unit in both the pre- and post-policy period and two economics price indexes to estimate the expenditure reduction in Ontario. Further, we used the post-policy Ontario prices to estimate the potential reduction in other provinces.We estimate that total expenditure on generic drugs in Ontario during the second half of 2010 was between $181 and $194 million below what would be expected if prices had remained at pre-policy level. Over half of the reduction in spending was due to savings on just 10 generic ingredients. If other provinces had matched Ontario's prices, their expenditures over during the latter half of 2010 would have been $445 million lower.We found that if Ontario's pricing scheme were adopted nationally, overall spending on generic drugs in Canada would drop at least $1.28 billion annually--a 5% decrease in total prescription drug expenditure. Other provinces should seriously consider both changes to their generic drug prices and the use of more competitive bulk purchasing policies.

Induction of fungal laccase production under solid state bioprocessing of new agroindustrial waste and its application on dye decolorization.

Science.gov (United States)

Akpinar, Merve; Ozturk Urek, Raziye

2017-06-01

Lignocellulosic wastes are generally produced in huge amounts worldwide. Peach waste of these obtained from fruit juice industry was utilized as the substrate for laccase production by Pleurotus eryngii under solid state bioprocessing (SSB). Its chemical composition was determined and this bioprocess was carried out under stationary conditions at 28 °C. The effects of different compounds; copper, iron, Tween 80, ammonium nitrate and manganese, and their variable concentrations on laccase production were investigated in detail. The optimum production of laccase (43,761.33 ± 3845 U L -1 ) was achieved on the day of 20 by employing peach waste of 5.0 g and 70 µM Cu 2+ , 18 µM Fe 2+ , 0.025% (v/v) Tween 80, 4.0 g L -1 ammonium nitrate, 750 µM Mn 2+ as the inducers. The dye decolorization also researched to determine the degrading capability of laccase produced from peach culture under the above-mentioned conditions. Within this scope of the study, methyl orange, tartrazine, reactive red 2 and reactive black dyes were treated with this enzyme. The highest decolorization was performed with methyl orange as 43 ± 2.8% after 5 min of treatment when compared to other dyes. Up to now, this is the first report on the induction of laccase production by P. eryngii under SSB using peach waste as the substrate.

17 CFR 230.135a - Generic advertising.

Science.gov (United States)

2010-04-01

... 17 Commodity and Securities Exchanges 2 2010-04-01 2010-04-01 false Generic advertising. 230.135a Section 230.135a Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION GENERAL RULES AND REGULATIONS, SECURITIES ACT OF 1933 General § 230.135a Generic advertising. (a) For the purposes only of...

78 FR 59911 - Generic Information Collection for Land Management Planning

Science.gov (United States)

2013-09-30

... DEPARTMENT OF AGRICULTURE Forest Service Generic Information Collection for Land Management... organizations on the proposed information collection, Generic Information Collection for Land Management... related to forest management. The intent of this generic information collection request (ICR) is to...

Generic substitution: micro evidence from register data in Norway.

Science.gov (United States)

Dalen, Dag Morten; Furu, Kari; Locatelli, Marilena; Strøm, Steinar

2011-02-01

The importance of prices, doctor and patient characteristics, and market institutions for the likelihood of choosing generic drugs instead of the more expensive original brand-name version are examined. Using an extensive dataset extracted from The Norwegian Prescription Database containing all prescriptions dispensed to individuals in February 2004 and 2006 on 23 different drugs (chemical substances) in Norway, we find strong evidence for the importance of both doctor and patient characteristics for the choice probabilities. The price difference between brand and generic versions and insurance coverage both affect generic substitution. Moreover, controlling for the retail chain affiliation of the dispensing pharmacy, we find that pharmacies play an important role in promoting generic substitution. In markets with more recent entry of generic drugs, brand-name loyalty proves to be much stronger, giving less explanatory power to our demand model.

Generic drug policy in Australia: a community pharmacy perspective

Science.gov (United States)

Beecroft, Grahame

2007-01-01

This article provides a commentary, from a community pharmacy perspective, on the policy environment for the pharmacy sector in Australia, with a particular focus on present challenges arising from proposals to achieve substantial PBS cost savings from an anticipated surge of new generic drugs. Some $2 billion of medicines currently on the PBS will come off patent in the next 4 years. This growth comes from a low base where generics currently account for only 15% of the total PBS budget. Remuneration for PBS dispensing is fixed through five year agreements with the government, so trading terms on generics are important for the cross-subsidy of other dispensing activities and professional services. These trading terms (discounts provided by generics suppliers) have become part of the overall cost and revenue structure of pharmacies. Despite these arrangements, generic substitution rates in Australia are lower than in most comparable countries, which the government views as an opportunity to promote generic use. The future of generic drug supply via the PBS is important to allow consumers access to medications at the lowest possible price and to provide space for PBS listing of new and expensive drugs. But considerations of PBS reform need to take account of the role and viability of community pharmacy sector as provider of pharmaceuticals in a timely and efficient manner to Australian residents. PMID:17543112

Do higher-priced generic medicines enjoy a competitive advantage under reference pricing?

Science.gov (United States)

Puig-Junoy, Jaume

2012-11-01

In many countries with generic reference pricing, generic producers and distributors compete by means of undisclosed discounts offered to pharmacies in order to reduce acquisition costs and to induce them to dispense their generic to patients in preference over others. The objective of this article is to test the hypothesis that under prevailing reference pricing systems for generic medicines, those medicines sold at a higher consumer price may enjoy a competitive advantage. Real transaction prices for 179 generic medicines acquired by pharmacies in Spain have been used to calculate the discount rate on acquisition versus reimbursed costs to pharmacies. Two empirical hypotheses are tested: the discount rate at which pharmacies acquire generic medicines is higher for those pharmaceutical presentations for which there are more generic competitors; and, the discount rate at which pharmacies acquire generic medicines is higher for those pharmaceutical forms for which the consumer price has declined less in relation to the consumer price of the brand drug before generic entry (higher-priced generic medicines). An average discount rate of 39.3% on acquisition versus reimbursed costs to pharmacies has been observed. The magnitude of the discount positively depends on the number of competitors in the market. The higher the ratio of the consumer price of the generic to that of the brand drug prior to generic entry (i.e. the smaller the price reduction of the generic in relation to the brand drug), the larger the discount rate. Under reference pricing there is intense price competition among generic firms in the form of unusually high discounts to pharmacies on official ex-factory prices reimbursed to pharmacies. However, this effect is highly distorting because it favours those medicines with a higher relative price in relation to the brand price before generic entry.

Comparative effectiveness of generic versus brand-name antiepileptic medications.

Science.gov (United States)

Gagne, Joshua J; Kesselheim, Aaron S; Choudhry, Niteesh K; Polinski, Jennifer M; Hutchins, David; Matlin, Olga S; Brennan, Troyen A; Avorn, Jerry; Shrank, William H

2015-11-01

The objective of this study was to compare treatment persistence and rates of seizure-related events in patients who initiate antiepileptic drug (AED) therapy with a generic versus a brand-name product. We used linked electronic medical and pharmacy claims data to identify Medicare beneficiaries who initiated one of five AEDs (clonazepam, gabapentin, oxcarbazepine, phenytoin, zonisamide). We matched initiators of generic versus brand-name versions of these drugs using a propensity score that accounted for demographic, clinical, and health service utilization variables. We used a Cox proportional hazards model to compare rates of seizure-related emergency room (ER) visit or hospitalization (primary outcome) and ER visit for bone fracture or head injury (secondary outcome) between the matched generic and brand-name initiators. We also compared treatment persistence, measured as time to first 14-day treatment gap, between generic and brand-name initiators. We identified 19,760 AED initiators who met study eligibility criteria; 18,306 (93%) initiated a generic AED. In the matched cohort, we observed 47 seizure-related hospitalizations and ER visits among brand-name initiators and 31 events among generic initiators, corresponding to a hazard ratio of 0.53 (95% confidence interval, 0.30 to 0.96). Similar results were observed for the secondary clinical endpoint and across sensitivity analyses. Mean time to first treatment gap was 124.2 days (standard deviation [sd], 125.8) for brand-name initiators and 137.9 (sd, 148.6) for generic initiators. Patients who initiated generic AEDs had fewer adverse seizure-related clinical outcomes and longer continuous treatment periods before experiencing a gap than those who initiated brand-name versions. Copyright © 2015 Elsevier Inc. All rights reserved.

Generic Assessment Criteria for human health risk assessment of potentially contaminated land in China.

Science.gov (United States)

Cheng, Yuanyuan; Nathanail, Paul C

2009-12-20

Generic Assessment Criteria (GAC) are derived using widely applicable assumptions about the characteristics and behaviour of contaminant sources, pathways and receptors. GAC provide nationally consistent guidance, thereby saving money and time. Currently, there are no human health based Generic Assessment Criteria (GAC) for contaminated sites in China. Protection of human health is therefore difficult to ensure and demonstrate; and the lack of GAC makes it difficult to tell if there is potential significant risk to human health unless site-specific criteria are derived. This paper derived Chinese GAC (GAC) for five inorganic and eight organic substances for three regions in China for three land uses: urban residential without plant uptake, Chinese cultivated land, and commercial/industrial using the SNIFFER model. The SNIFFER model has been further implemented with a dermal absorption algorithm and the model default input values have been changed to reflect the Chinese exposure scenarios. It is envisaged that the modified SNIFFER model could be used to derive GAC for more contaminants, more Regions, and more land uses. Further research to enhance the reliability and acceptability of the GAC is needed in regional/national surveys in diet and working patterns.

Assessment of the critical engineering data needs for the commercialization of magnetic confinement fusion

International Nuclear Information System (INIS)

Waganer, L.M.; Zuckerman, D.S.

1983-01-01

A survey of twenty-two recent conceptual fusion reactor designs was conducted to ascertain both generic and specific engineering data needs critical for the commercialization of magnetic confinement fusion (MCF). Design experts or advocates for each concept were queried as to the more critical engineering issues and data needs affecting the achievement of commercialization. For each concept, the technical issues were identified and the data needs quantified. Issues and data needs were then ranked based upon the experts' perceptions of the relative importance of each to the concept. The issues encompassed all aspects of the fusion reactor plant design including materials, performance, maintainability, operability, cost, safety and resources

Generic drugs: Review and experiences from South India

Directory of Open Access Journals (Sweden)

Philip Mathew

2015-01-01

Full Text Available The cost of pharmaceuticals, as a percentage of total healthcare spending, has been rising worldwide. This has resulted in strained national budgets and a high proportion of people without access to essential medications. Though India has become a global hub of generic drug manufacturing, the expected benefits of cheaper drugs are not translating into savings for ordinary people. This is in part due to the rise of branded generics, which are marketed at a price point close to the innovator brands. Unbranded generic medicines are not finding their way into prescriptions due to issues of confidence and perception, though they are proven to be much cheaper and comparable in efficacy to branded medicines. The drug inventory of unbranded generic manufacturers fares reasonably when reviewed using the World Health Organization-Health Action International (WHO-HAI tool for analysing drug availability. Also, unbranded generic medicines are much cheaper when compared to the most selling brands and they can bring down the treatment costs in primary care and family practice. We share our experience in running a community pharmacy for an urban health center in the Pathanamthitta district of Kerala State, which is run solely on generic medicines. The drug availability at the community pharmacy was 73.3% when analyzed using WHO-HAI tool and the savings for the final consumers were up to 93.1%, when compared with most-selling brand of the same formulation.

What do people really think of generic medicines? A systematic review and critical appraisal of literature on stakeholder perceptions of generic drugs.

LENUS (Irish Health Repository)

Dunne, Suzanne S

2015-07-01

Considerable emphasis is presently being placed on usage of generic medicines by governments focussed on the potential economic benefits associated with their use. Concurrently, there is increasing discussion in the lay media of perceived doubts regarding the quality and equivalence of generic medicines. The objective of this paper is to report the outcomes of a systematic search for peer-reviewed, published studies that focus on physician, pharmacist and patient\\/consumer perspectives of generic medicines.

How Abbott’s Fenofibrate Franchise Avoided Generic Competition

Science.gov (United States)

Downing, Nicholas S.; Ross, Joseph S.; Jackevicius, Cynthia A.; Krumholz, Harlan M.

2013-01-01

The ongoing debate concerning the efficacy of fenofibrate has overshadowed an important aspect of the drug’s history: Abbott, the maker of branded fenofibrate, has produced several bioequivalent reformulations, which dominate the market even though generic fenofibrate has been available for almost a decade. This continued use of branded formulations, which cost twice as much as generic versions of fenofibrate, imposes an annual cost of approximately $700 million on our healthcare system. Abbott maintained its dominance of the fenofibrate market, in part, through a complex switching strategy involving the sequential launch of branded reformulations that had not been shown to be superior to the first generation product and patent litigation that delayed the approval of generic formulations. The small differences in dose of the newer branded formulations prevented substitution with generics of older generation products. As soon as direct generic competition seemed likely at the new dose level where substitution would be allowed, Abbott would launch another reformulation and the cycle would repeat. Our objective, using the fenofibrate example, is to describe how current policy can allow pharmaceutical companies to maintain market share using reformulations of branded medications without demonstrating the superiority of next generation products. PMID:22493409

Once more the generic name Passerina Vieillot

NARCIS (Netherlands)

Oort, van E.D.

1910-01-01

The note on the generic name of the Snow-bunting by Dr. E. Hartert in this part of our periodical gives me cause to revert to the subject of my note on the generic name Passerina Vieillot and to state here, that I stand to what I have said about the rejection of this name in Zoology (Notes Leyden

[Generic drugs and the consumption trends of antihypertensives in Morocco].

Science.gov (United States)

Berrada El Azizi, Ghizlane; Ahid, Samir; Ghanname, Imane; Ghannam, Imane; Belaiche, Abdelmajid; Hassar, Mohammed; Cherrah, Yahia

2013-01-01

To evaluate the evolution of consumption of antihypertensive drugs generic among 1991-2010, to assess the impacts after the institution of Mandatory Health Insurance and the marketing of generic drugs. We used sales data from the Moroccan subsidiary of IMS Health Intercontinental Marketing Service. Consumption of generic antihypertensive drugs increased from 0.08 to 10.65 DDD/1 000 inhabitants/day between 1991 and 2010. In 2010, generic of the calcium channel blockers (CCBs) represented 4.08 DDD/1 000 inhabitants/day (82.09%), followed by angiotensin converting enzyme inhibitors (ACEI) by 2.40 DDD/1 000 inhabitants/day (48.29%). The generics market of CCBs is the most dominant and represented in 2010, 79.21% in volume and 62.58% in value. In developing countries like Morocco, the generic drug is a key element for access to treatment especially for the poor population. © 2013 Société Française de Pharmacologie et de Thérapeutique.

[Analysis of generic drug supply in France].

Science.gov (United States)

Taboulet, F; Haramburu, F; Latry, Ph

2003-09-01

The list of generic medicines (LGM), published since 1997 by the Agence Française de Sécurité Sanitaire des Produits de Santé (AFFSSaPS), the French Medicine Agency, concerns a special part of the medicines reimbursed by the National Health Insurance (Social Security). The objectives of the present study were: i) to describe the components of this list, based on pharmaceutical, economical and therapeutic characteristics, ii) to study differences between generic and reference products (formulations, excipients, prices, etc.), iii) to analyze information on excipients provided to health care professionals. The 21st version of the LGM (April 2001) was used. Therapeutic value was retrieved from the 2001 AFSSaPS report on the therapeutic value of 4490 reimbursed medicines. Information on excipients in the LGM and the Vidal dictionary (reference prescription book in France) was compared. The products included in the LGM represent 20% of all reimbursed medicines. The mean price differences between generics and their reference products vary between 30 and 50% for more than two thirds of the generic groups. The therapeutic value of the products of the LGM was judged important in 71% of cases (vs 63% for the 4409 assessed medicines) and insufficient in 13% of cases (vs 19%). Information on excipients is often missing and sometimes erroneous. Although the LGM is regularly revised and thus the generic market in perpetual change, the 2001 cross description of this pharmaceutical market provides much informations and raises some concern.

Evaluation of generic and branded herbicides : technical report.

Science.gov (United States)

2015-03-01

As with other generic brand products in the marketplace, generic herbicides often have a lower initial product cost than : their brand-name counterparts. While the purchase price of herbicides is important to TxDOT, it is essential to look at : more ...

Investigations on a global environment improving technology utilizing biological functions. 2. Structuring a ligno-bioprocess; Seibutsu kino wo riyoshita chikyu kankyo kaizen gijutsu ni kansuru chosa. 2. Riguno bio process no kochiku

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-03-01

Discussions were given to reserve global environments on reducing dependence on fossil resources and more effectively utilizing wood resources. Economically utilizable amount of wastes from lumbering factories reaches about five million tons annually. Discussions were made on a ligno-bioprocess that uses these wastes. The current quantitative production efficiency of cellulase by means of bacterial breeding is very high. A problem is production of ligninolytic enzymes, to which application of the recombinant DNA method is indispensable. Combination of steam explosion with biological decomposition or the organosolv process is an effective method for lignin decomposition. Decomposition of cellulose by using the ultra critical water method is worth noticing. With respect to hemicellulose utilization, production of cellulose derivatives, biodegradable polymers and oligosaccharides would be conceivable by means of esterification and etherification. Vanillinic acid, adhesives, resins and lignin-based polymer materials could be manufactured from lignin. Material cost for these products accounts for about 35% of the product price, thus making the lignochemicals promising commercial products. 301 refs., 71 figs., 39 tabs.

Automated analysis in generic groups

Science.gov (United States)

Fagerholm, Edvard

This thesis studies automated methods for analyzing hardness assumptions in generic group models, following ideas of symbolic cryptography. We define a broad class of generic and symbolic group models for different settings---symmetric or asymmetric (leveled) k-linear groups --- and prove ''computational soundness'' theorems for the symbolic models. Based on this result, we formulate a master theorem that relates the hardness of an assumption to solving problems in polynomial algebra. We systematically analyze these problems identifying different classes of assumptions and obtain decidability and undecidability results. Then, we develop automated procedures for verifying the conditions of our master theorems, and thus the validity of hardness assumptions in generic group models. The concrete outcome is an automated tool, the Generic Group Analyzer, which takes as input the statement of an assumption, and outputs either a proof of its generic hardness or shows an algebraic attack against the assumption. Structure-preserving signatures are signature schemes defined over bilinear groups in which messages, public keys and signatures are group elements, and the verification algorithm consists of evaluating ''pairing-product equations''. Recent work on structure-preserving signatures studies optimality of these schemes in terms of the number of group elements needed in the verification key and the signature, and the number of pairing-product equations in the verification algorithm. While the size of keys and signatures is crucial for many applications, another aspect of performance is the time it takes to verify a signature. The most expensive operation during verification is the computation of pairings. However, the concrete number of pairings is not captured by the number of pairing-product equations considered in earlier work. We consider the question of what is the minimal number of pairing computations needed to verify structure-preserving signatures. We build an

Performance measures in the earth observations commercialization applications program

Science.gov (United States)

Macauley, Molly K.

1996-03-01

Performance measures in the Earth Observations Commercialization Application Program (EOCAP) are key to its success and include net profitability; enhancements to industry productivity through generic innovations in industry practices, standards, and protocols; and documented contributions to public policy governing the newly developing remote sensing industry. Because EOCAP requires company co-funding, both parties to the agreement (the government and the corporate partner) have incentives to pursue these goals. Further strengthening progress towards these goals are requirements for business plans in the company's EOCAP proposal, detailed scrutiny given these plans during proposal selection, and regularly documented progress reports during project implementation.

Impact of alternative interventions on changes in generic dispensing rates.

Science.gov (United States)

O'Malley, A James; Frank, Richard G; Kaddis, Atheer; Rothenberg, Barbara M; McNeil, Barbara J

2006-10-01

To evaluate the effectiveness of four alternative interventions (member mailings, advertising campaigns, free generic drug samples to physicians, and physician financial incentives) used by a major health insurer to encourage its members to switch to generic drugs. Using claim-level data from Blue Cross Blue Shield of Michigan, we evaluated the success of four interventions implemented during 2000-2003 designed to increase the use of generic drugs among its members. Around 13 million claims involving seven important classes of drugs were used to assess the effectiveness of the interventions. For each intervention a control group was developed that most closely resembled the corresponding intervention group. Logistic regression models with interaction effects between the treatment group (intervention versus control) and the status of the intervention (active versus not active) were used to evaluate if the interventions had an effect on the generic dispensing rate (GDR). Because the mail order pharmacy was considered more aggressive at converting prescriptions to generics, separate generic purchasing models were fitted to retail and mail order claims. In secondary analyses separate models were also fitted to claims involving a new condition and claims refilled for preexisting conditions. The interventions did not appear to increase the market penetration of generic drugs for either retail or mail order claims, or for claims involving new or preexisting conditions. In addition, we found that the ratio of copayments for brand name to generic drugs had a large positive effect on the GDR. The interventions did not appear to directly influence the GDR. Financial incentives expressed to consumers through benefit designs have a large influence on their switching to generic drugs and on the less-costly mail-order mode of purchase.

Radiation analysis for a generic centralized interim storage facility

International Nuclear Information System (INIS)

Gillespie, S.G.; Lopez, P.; Eble, R.G.

1997-01-01

This paper documents the radiation analysis performed for the storage area of a generic Centralized Interim Storage Facility (CISF) for commercial spent nuclear fuel (SNF). The purpose of the analysis is to establish the CISF Protected Area and Restricted Area boundaries by modeling a representative SNF storage array, calculating the radiation dose at selected locations outside the storage area, and comparing the results with regulatory radiation dose limits. The particular challenge for this analysis is to adequately model a large (6000 cask) storage array with a reasonable amount of analysis time and effort. Previous analyses of SNF storage systems for Independent Spent Fuel Storage Installations at nuclear plant sites (for example in References 5.1 and 5.2) had only considered small arrays of storage casks. For such analyses, the dose contribution from each storage cask can be modeled individually. Since the large number of casks in the CISF storage array make such an approach unrealistic, a simplified model is required

Bio-processing of solid wastes and secondary resources for metal extraction - A review.

Science.gov (United States)

Lee, Jae-Chun; Pandey, Banshi Dhar

2012-01-01

Metal containing wastes/byproducts of various industries, used consumer goods, and municipal waste are potential pollutants, if not treated properly. They may also be important secondary resources if processed in eco-friendly manner for secured supply of contained metals/materials. Bio-extraction of metals from such resources with microbes such as bacteria, fungi and archaea is being increasingly explored to meet the twin objectives of resource recycling and pollution mitigation. This review focuses on the bio-processing of solid wastes/byproducts of metallurgical and manufacturing industries, chemical/petrochemical plants, electroplating and tanning units, besides sewage sludge and fly ash of municipal incinerators, electronic wastes (e-wastes/PCBs), used batteries, etc. An assessment has been made to quantify the wastes generated and its compositions, microbes used, metal leaching efficiency etc. Processing of certain effluents and wastewaters comprising of metals is also included in brief. Future directions of research are highlighted. Copyright © 2011 Elsevier Ltd. All rights reserved.

Invitro Study on the Fluid From Banana Stem Bioprocess as Direct Fed Microbial

Science.gov (United States)

Mutaqin, B. K.; Tanuwiria, U. H.; Hernawan, E.

2018-02-01

The purpose of this research was to study the liquid produced by the bioprocess of banana stem as a Direct Fed Microbial (DFM) in order to enhance local sheep productivity invitro. Studying was the use of DFM in two invitro feeds. The object observed in this research was fermentability and digestibility value. The method was experimental with the experimental design, i.e. factorial experimental design with two factors. The first factor was DFM, the levels of which were 0, 0,2, 0,4 and 0,6%, while the second factor was two feed types (complete feed and Pennisetum purpureum only) with the treatment of threefold repetition. This research showed that fermentability and digestibility value were influenced by the DFM in the invitro complete feed. The research result analyzed using MANOVA with further testing using Duncan Test. The conclusion of the research result were shows the interaction DFM in the complete feed improve fermentability and digestibility values and DFM 0,6% shows the highest value.

Commercial/industrial photovoltaic module and array requirement study. Low-cost solar array project engineering area

Science.gov (United States)

1981-01-01

Design requirements for photovoltaic modules and arrays used in commercial and industrial applications were identified. Building codes and referenced standards were reviewed for their applicability to commercial and industrial photovoltaic array installation. Four general installation types were identified - integral (replaces roofing), direct (mounted on top of roofing), stand-off (mounted away from roofing), and rack (for flat or low slope roofs, or ground mounted). Each of the generic mounting types can be used in vertical wall mounting systems. This implies eight mounting types exist in the commercial/industrial sector. Installation costs were developed for these mounting types as a function of panel/module size. Cost drivers were identified. Studies were performed to identify optimum module shapes and sizes and operating voltage cost drivers. The general conclusion is that there are no perceived major obstacles to the use of photovoltaic modules in commercial/industrial arrays.

Leveraging consumer's behaviour to promote generic drugs in Italy.

Science.gov (United States)

Zerbini, Cristina; Luceri, Beatrice; Vergura, Donata Tania

2017-04-01

The aim of this study was to fill the lack of knowledge regarding a more grounded exploration of the consumer's decision-making process in the context of generic drugs. In this perspective, a model, within the theoretical framework of the Theory of Planned Behaviour (TPB), for studying the consumers' purchase intention of generic drugs was developed. An online survey on 2,222 Italian people who bought drugs in the past was conducted. The proposed model was tested through structural equation modelling (SEM). Almost all the constructs considered in the model, except the perceived behavioural control, contribute to explain the consumer's purchase intention of generic drugs, after controlling for demographic variables (age, income, education). Specifically, attitude, subjective norm, past behaviour, self-identity and trust in the pharmacist have a positive influence on the intention to buy generic drugs. On the contrary, perceived risk towards products and brand sensitivity act negatively. The results of the present study could be useful to public policy makers in developing effective policies and educational campaigns aimed at promoting generic drugs. Specifically, marketing efforts should be directed to inform consumers about the generic drugs' characteristics to mitigate the perceived risk towards these products and to raise awareness during their decision-making process. Copyright © 2017 Elsevier B.V. All rights reserved.

Simultaneous production of lipases and biosurfactants by submerged and solid-state bioprocesses.

Science.gov (United States)

Colla, Luciane Maria; Rizzardi, Juliana; Pinto, Marta Heidtmann; Reinehr, Christian Oliveira; Bertolin, Telma Elita; Costa, Jorge Alberto Vieira

2010-11-01

Lipases and biosurfactants are compounds produced by microorganisms generally involved in the metabolization of oil substrates. However, the relationship between the production of lipases and biosurfactants has not been established yet. Therefore, this study aimed to evaluate the correlation between production of lipases and biosurfactants by submerged (SmgB) and solid-state bioprocess (SSB) using Aspergillus spp., which were isolated from a soil contaminated by diesel oil. SSB had the highest production of lipases, with lipolytic activities of 25.22U, while SmgB had 4.52U. The production of biosurfactants was not observed in the SSB. In the SmgB, correlation coefficients of 91% and 87% were obtained between lipolytic activity and oil in water and water in oil emulsifying activities, respectively. A correlation of 84% was obtained between lipolytic activity and reduction of surface tension in the culture medium. The surface tension decreased from 50 to 28mNm(-1) indicating that biosurfactants were produced in the culture medium. Copyright 2010 Elsevier Ltd. All rights reserved.

Bioprocess iterative batch-to-batch optimization based on hybrid parametric/nonparametric models.

Science.gov (United States)

Teixeira, Ana P; Clemente, João J; Cunha, António E; Carrondo, Manuel J T; Oliveira, Rui

2006-01-01

This paper presents a novel method for iterative batch-to-batch dynamic optimization of bioprocesses. The relationship between process performance and control inputs is established by means of hybrid grey-box models combining parametric and nonparametric structures. The bioreactor dynamics are defined by material balance equations, whereas the cell population subsystem is represented by an adjustable mixture of nonparametric and parametric models. Thus optimizations are possible without detailed mechanistic knowledge concerning the biological system. A clustering technique is used to supervise the reliability of the nonparametric subsystem during the optimization. Whenever the nonparametric outputs are unreliable, the objective function is penalized. The technique was evaluated with three simulation case studies. The overall results suggest that the convergence to the optimal process performance may be achieved after a small number of batches. The model unreliability risk constraint along with sampling scheduling are crucial to minimize the experimental effort required to attain a given process performance. In general terms, it may be concluded that the proposed method broadens the application of the hybrid parametric/nonparametric modeling technique to "newer" processes with higher potential for optimization.

Predictors of generic substitution: The role of psychological, sociodemographic, and contextual factors.

Science.gov (United States)

Drozdowska, Aleksandra; Hermanowski, Tomasz

2016-01-01

Escalating pharmaceutical costs have become a global challenge for both governments and patients. Generic substitution is one way of decreasing these costs. The aim of this study was to investigate factors associated with patients' choice between generic drugs and innovator drugs. The survey was conducted in June 2013, 1000 people from across Poland were chosen as a representative population sample. The outcome (a preference for generics/a preference for innovator pharmaceuticals/no preference) was modeled by multinomial logistic regression, adjusted for several variables describing patients' sensitivity to selected generic features (price, brand, and country of origin), to third-party opinions about generics (information on generics in the mass media, opinions of health professionals (i.e. physicians, pharmacists), relatives/friends), as well as patients' personal experiences and income per household. The results supported the predictive capacity of most independent variables (except for patient sensitivity to the country of origin and to the information on generics in the mass media), denoting patients' preferences toward generic substitution. Patient sensitivity to recommendations by physicians, generic brand, and household income were the strongest predictors of the choice between generic and innovator pharmaceuticals (P brand or their physician's opinion, as well as in respondents who were sensitive to recommendations by pharmacists or attached a greater value to a past experience with generics (their own experience or that of relatives/friends). In consideration of the foregoing, awareness-raising campaigns may be recommended, supported by a variety of systemic solutions and tools to encourage generic substitution. Copyright © 2016 Elsevier Inc. All rights reserved.

Generic nuclear power plant component failure data bank

International Nuclear Information System (INIS)

Araujo Goes, A.G. de; Gibelli, S.M.O.

1988-11-01

This report consist in the development of a generic nuclear power plant component failure data bank. This data bank was implemented in a PC-XT microcomputer, IBM compatible, using the Open Access II program. Generic failure data tables for Westinghouse nuclear power plants and for general PWR power plants are presented. They are the final product of a research which included a preselection and a selection of data collected from the available sources in the library of CNEN (National Nuclear Energy Commission) and from the CIN/CNEN (Neclear Information Center). Futhermore, a proposal of evaluating models of average failure rates of pumps and valves are also presented. Through the electronic data bank one can easily have a generic view of failure rate ranges as well as failure models foe a certain component. It is very importante to develop procedures to collect and store generic failure data that can be quickly accessed, in order to update the Probabilistic Safety Study of Angra-1 and to used in studies which may have component failures of nuclear power plant safety systems. In the future, data specialization can be achieved by means of statistical calculations involving specific data collected from the operational experience of Angra-1 nuclear power plant and the generic data bank. (author) [pt

Simplex-based optimization of numerical and categorical inputs in early bioprocess development: Case studies in HT chromatography.

Science.gov (United States)

Konstantinidis, Spyridon; Titchener-Hooker, Nigel; Velayudhan, Ajoy

2017-08-01

Bioprocess development studies often involve the investigation of numerical and categorical inputs via the adoption of Design of Experiments (DoE) techniques. An attractive alternative is the deployment of a grid compatible Simplex variant which has been shown to yield optima rapidly and consistently. In this work, the method is combined with dummy variables and it is deployed in three case studies wherein spaces are comprised of both categorical and numerical inputs, a situation intractable by traditional Simplex methods. The first study employs in silico data and lays out the dummy variable methodology. The latter two employ experimental data from chromatography based studies performed with the filter-plate and miniature column High Throughput (HT) techniques. The solute of interest in the former case study was a monoclonal antibody whereas the latter dealt with the separation of a binary system of model proteins. The implemented approach prevented the stranding of the Simplex method at local optima, due to the arbitrary handling of the categorical inputs, and allowed for the concurrent optimization of numerical and categorical, multilevel and/or dichotomous, inputs. The deployment of the Simplex method, combined with dummy variables, was therefore entirely successful in identifying and characterizing global optima in all three case studies. The Simplex-based method was further shown to be of equivalent efficiency to a DoE-based approach, represented here by D-Optimal designs. Such an approach failed, however, to both capture trends and identify optima, and led to poor operating conditions. It is suggested that the Simplex-variant is suited to development activities involving numerical and categorical inputs in early bioprocess development. © 2017 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Addition of generic medication vouchers to a pharmacist academic detailing program: effects on the generic dispensing ratio in a physician-hospital organization.

Science.gov (United States)

Bhargava, Vinay; Greg, Mark E; Shields, Mark C

2010-01-01

Generic dispensing ratio (GDR) is an important measure of efficiency in pharmacy benefit management. A few studies have examined the effects of academic detailing or generic drug samples on GDR. On July 1, 2007, a physician-hospital organization (PHO) with a pay-for-performance incentive for generic utilization initiated a pilot generic medication voucher program that augmented its existing pharmacist-led academic detailing efforts. No published studies have examined the role of generic medication vouchers in promoting generic drug utilization. To determine if supplementing an existing academic detailing initiative in a PHO with a generic medication voucher program would be more effective in increasing the GDR compared with academic detailing alone. The intervention took place over the 9-month period from July 1, 2007, through March 31, 2008. Vouchers provided patients with the first fill of a 30-day supply of a generic drug at no cost to the patient for 8 specific generic medications obtained through a national community pharmacy chain. The study was conducted in a PHO composed of 7 hospitals and approximately 2,900 physicians (900 primary care providers [PCPs] and 2,000 specialists). Of the approximately 300 PCP practices, 21 practices with at least 2 physicians each were selected on the basis of high prescription volume (more than 500 pharmacy claims for the practice over a 12-month pre-baseline period) and low GDR (practice GDR less than 55% in the 12-month pre-baseline period). These 21 practices were then randomized to a control group of academic detailing alone or the intervention group that received academic detailing plus generic medication vouchers. One of 10 intervention groups declined to participate, and 2 of 11 control groups dropped out of the PHO. GDR was calculated monthly for all pharmacy claims including the 8 voucher medications. GDR was defined as the ratio of the total number of paid generic pharmacy claims divided by the total number of paid

Using Service Oriented Architecture in a Generic Virtual Power Plant

DEFF Research Database (Denmark)

Andersen, Peter Bach; Poulsen, Bjarne; Træholt, Chresten

2009-01-01

The purpose of this paper is to find and describe a suitable software framework that can be used to help implement the concept of a Generic Virtual Power Plant in the future power system. The Generic Virtual Power Plant concept, along with the utilization of distributed energy resources, has many...... the Generic Virtual Power Plant, an array of different software design principles, patterns and architectures must be applied. Especially Service Oriented Architecture (SOA) can aid in implementing the Generic Virtual Power Plant.......The purpose of this paper is to find and describe a suitable software framework that can be used to help implement the concept of a Generic Virtual Power Plant in the future power system. The Generic Virtual Power Plant concept, along with the utilization of distributed energy resources, has many...... interesting properties that can influence the future shape of power markets. The concept holds many promises including cheaper power to the consumer, a more flexible and responsive power production and the support of a more environment-friendly development. In order to realize a software solution supporting...

Generic tacrolimus in solid organ transplantation

DEFF Research Database (Denmark)

Taube, D; Jones, G; O'Beirne, J

2014-01-01

The availability of a wide range of immunosuppressive therapies has revolutionized the management of patients who have undergone solid organ transplantation (SOT). However, the cost of immunosuppressive drugs remains high. This situation has led to the development of generic equivalents, which...... innovator tacrolimus drug (Prograf) in both healthy volunteers and kidney transplant patients. Clinical experience with this generic tacrolimus formulation has also been established in both de novo and conversion patients who have undergone kidney and liver transplantation, as well as in conversion of other...

Generic immunosuppression in transplantation: current evidence and controversial issues.

Science.gov (United States)

El Hajj, Sandra; Kim, Miae; Phillips, Karen; Gabardi, Steven

2015-05-01

The overall success of organ transplantation in the 21st century has been predicated, in part, on the use of newer, more potent, and selective immunosuppressive agents. However, the high cost of lifelong immunosuppression represents a financial burden for many patients. In the past 15 years, regulatory agencies in Europe and America have approved several generic immunosuppressants. One concern is whether the conversion between innovator and generic immunosuppressants will prove to be problematic. This manuscript aims to compare and contrast the bioequivalence requirements among regulatory authorities in the USA, Europe, and Canada, evaluate published studies of generic immunosuppressants in transplant recipients, summarize consensus statements made by transplant organizations and discuss how to engage patients in discussion regarding the choice between innovator and generic immunosuppressants.

Lawsuits allege price fixing by generic drug makers

Directory of Open Access Journals (Sweden)

Robbins RA

2016-12-01

Full Text Available No abstract available. Article truncated at 150 words. Two years after high generic drug prices became a public controversy, Reuters is reporting that 20 states filed a lawsuit Thursday against Mylan, Teva Pharmaceuticals and four other generic drug makers (1. The suit alleges the companies conspired to fix prices or allocated markets to prop up prices. The civil lawsuit, led by antitrust investigators in Connecticut, comes one day after the U.S. Department of Justice filed criminal charges against two former executives of the generic drug maker, Heritage. The states attorneys general asked the court to order the companies to disgorge ill-gotten gains, which were not defined, pay attorneys' fees and stop collusion. Of the states in the Southwest only Nevada is participating in the lawsuit. The cases are part of a broader generic drug pricing probe that remains under way at the state and federal level, as well as in the U.S. Congress. In 2014, media reports of …

Influence of multiple bioprocess parameters on production of lipase from Pseudomonas sp. BWS-5

Directory of Open Access Journals (Sweden)

Balwinder Singh Sooch

2013-10-01

Full Text Available The aim of the present work was to study the influence of multiple bioprocess parameters for the maximum production of lipase from Pseudomonas sp. BWS-5. The culture reached the stationary phase of growth after 36h of incubation when the maximum lipase production was obtained at flask level. The different media components such as carbon sources, nitrogen sources, trace elements and process parameters such as the pH of the medium, temperature and time of incubation, agitation/stationary conditions, etc. were optimized at flask level and at bioreactor level. The maximum enzyme production of 298 IU/mL was obtained with the use of simple medium with pH 6.5 containing glucose (1 %, w/v, peptone (3 %, w/v and KCl (0.05 %, w/v after 30h of incubation at 37°C under agitation (200 rpm conditions with 0.75 vvm of air supply.

Mixed WTO ruling on generic drug development.

Science.gov (United States)

Elliott, R

2000-01-01

On 17 March 2000, the World Trade Organization upheld the provision in Canada's patent laws that allows generic drug manufacturers to develop (but not sell) their cheaper versions of patented medicines before the 20-year patients expire. The decision prevents pharmaceutical companies from enjoying market monopolies beyond their patent terms, avoiding what would otherwise be even lengthier delays in the sale of cheaper, generic drugs in Canada. This decision is of significance not only to Canada, but also to other WTO member countries and to all individuals who use pharmaceutical products. However, the decision is not all positive: the WTO also ruled that Canada is violating international agreements by letting generic manufacturers stockpile their versions of patented drugs before patents expire. This article explains the issues, the arguments, and the decision.

40 CFR 721.10036 - Acetaldehyde based polymer (generic).

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Acetaldehyde based polymer (generic... Specific Chemical Substances § 721.10036 Acetaldehyde based polymer (generic). (a) Chemical substance and... based polymer (PMN P-02-406) is subject to reporting under this section for the significant new uses...

Enhancing Safety through Generic Competencies

Directory of Open Access Journals (Sweden)

S. Mockel

2014-03-01

Full Text Available This article provides insights into proactive safety management and mitigation. An analysis of accident reports reveals categories of supervening causes of accidents which can be directly linked to the concept of generic competencies (information management, communication and coordination, problem solving, and effect control. These findings strongly suggest adding the human element as another safety-constituting pillar to the concept of ship safety next to technology and regulation. We argue that the human element has unique abilities in dealing with critical and highly dynamic situations which can contribute to the system's recovery from non-routine or critical situations. By educating seafarers in generic competencies we claim to enable the people onboard to successfully deal with critical situations.

Generic magnetic fusion reactor cost assessment

International Nuclear Information System (INIS)

Sheffield, J.

1985-01-01

The Fusion Energy Division of the Oak Ridge National Laboratory discusses ''generic'' magnetic fusion reactors. The author comments on DT burning magnetic fusion reactor models being possibly operational in the 21st century. Representative parameters from D-T reactor studies are given, as well as a shematic diagram of a generic fusion reactor. Values are given for winding pack current density for existing and future superconducting coils. Topics included are the variation of the cost of electricity (COE), the dependence of the COE on the net electric power of the reactor, and COE formula definitions

The Draft Genome Sequence of Clostridium sp. Strain NJ4, a Bacterium Capable of Producing Butanol from Inulin Through Consolidated Bioprocessing.

Science.gov (United States)

Jiang, Yujia; Lu, Jiasheng; Chen, Tianpeng; Yan, Wei; Dong, Weiliang; Zhou, Jie; Zhang, Wenming; Ma, Jiangfeng; Jiang, Min; Xin, Fengxue

2018-05-23

A novel butanogenic Clostridium sp. NJ4 was successfully isolated and characterized, which could directly produce relatively high titer of butanol from inulin through consolidated bioprocessing (CBP). The assembled draft genome of strain NJ4 is 4.09 Mp, containing 3891 encoded protein sequences with G+C content of 30.73%. Among these annotated genes, a levanase, a hypothetical inulinase, and two bifunctional alcohol/aldehyde dehydrogenases (AdhE) were found to play key roles in the achievement of ABE production from inulin through CBP.

Generic radiation safety design for SSRL synchrotron radiation beamlines

Energy Technology Data Exchange (ETDEWEB)

Liu, James C. [Radiation Protection Department, Stanford Linear Accelerator Center (SLAC), MS 48, P.O. Box 20450, Stanford, CA 94309 (United States)]. E-mail: james@slac.stanford.edu; Fasso, Alberto [Radiation Protection Department, Stanford Linear Accelerator Center (SLAC), MS 48, P.O. Box 20450, Stanford, CA 94309 (United States); Khater, Hesham [Radiation Protection Department, Stanford Linear Accelerator Center (SLAC), MS 48, P.O. Box 20450, Stanford, CA 94309 (United States); Prinz, Alyssa [Radiation Protection Department, Stanford Linear Accelerator Center (SLAC), MS 48, P.O. Box 20450, Stanford, CA 94309 (United States); Rokni, Sayed [Radiation Protection Department, Stanford Linear Accelerator Center (SLAC), MS 48, P.O. Box 20450, Stanford, CA 94309 (United States)

2006-12-15

To allow for a conservative, simple, uniform, consistent, efficient radiation safety design for all SSRL beamlines, a generic approach has been developed, considering both synchrotron radiation (SR) and gas bremsstrahlung (GB) hazards. To develop the methodology and rules needed for generic beamline design, analytic models, the STAC8 code, and the FLUKA Monte Carlo code were used to pre-calculate sets of curves and tables that can be looked up for each beamline safety design. Conservative beam parameters and standard targets and geometries were used in the calculations. This paper presents the SPEAR3 beamline parameters that were considered in the design, the safety design considerations, and the main pre-calculated results that are needed for generic shielding design. In the end, the rules and practices for generic SSRL beamline design are summarized.

The generic strategy trap.

Science.gov (United States)

Miller, D

1992-01-01

Management experts claim that for a company to thrive, it must concentrate on a single generic strategy--on one thing it does better than its rivals. But specialization also has its disadvantages. The author suggests that a broader, mixed approach may be preferable.

Final generic environmental impact statement on decommissioning of nuclear facilities

International Nuclear Information System (INIS)

1988-08-01

This final generic environmental impact statement was prepared as part of the requirement for considering changes in regulations on decommissioning of commercial nuclear facilities. Consideration is given to the decommissioning of pressurized water reactors, boiling water reactors, research and test reactors, fuel reprocessing plants (FRPs) (currently, use of FRPs in the commercial sector is not being considered), small mixed oxide fuel fabrication plants, uranium hexafluoride conversion plants, uranium fuel fabrication plants, independent spent fuel storage installations, and non-fuel-cycle facilities for handling byproduct, source and special nuclear materials. Decommissioning has many positive environmental impacts such as the return of possibly valuable land to the public domain and the elimination of potential problems associated with increased numbers of radioactively contaminated facilities with a minimal use of resources. Major adverse impacts are shown to be routine occupational radiation doses and the commitment of nominally small amounts of land to radioactive waste disposal. Other impacts, including public radiation doses, are minor. Mitigation of potential health, safety, and environmental impacts requires more specific and detailed regulatory guidance than is currently available. Recommendations are made as to regulatory decommissioning particulars including such aspects as decommissioning alternatives, appropriate preliminary planning requirements at the time of commissioning, final planning requirements prior to termination of facility operations, assurance of funding for decommissioning, environmental review requirements. 26 refs., 7 figs., 68 tabs

A cross-sectional study examining the prevalence and risk factors for anti-microbial-resistant generic Escherichia coli in domestic dogs that frequent dog parks in three cities in south-western Ontario, Canada.

Science.gov (United States)

Procter, T D; Pearl, D L; Finley, R L; Leonard, E K; Janecko, N; Reid-Smith, R J; Weese, J S; Peregrine, A S; Sargeant, J M

2014-06-01

Anti-microbial resistance can threaten health by limiting treatment options and increasing the risk of hospitalization and severity of infection. Companion animals can shed anti-microbial-resistant bacteria that may result in the exposure of other dogs and humans to anti-microbial-resistant genes. The prevalence of anti-microbial-resistant generic Escherichia coli in the faeces of dogs that visited dog parks in south-western Ontario was examined and risk factors for shedding anti-microbial-resistant generic E. coli identified. From May to August 2009, canine faecal samples were collected at ten dog parks in three cities in south-western Ontario, Canada. Owners completed a questionnaire related to pet characteristics and management factors including recent treatment with antibiotics. Faecal samples were collected from 251 dogs, and 189 surveys were completed. Generic E. coli was isolated from 237 of the faecal samples, and up to three isolates per sample were tested for anti-microbial susceptibility. Eighty-nine percent of isolates were pan-susceptible; 82.3% of dogs shed isolates that were pan-susceptible. Multiclass resistance was detected in 7.2% of the isolates from 10.1% of the dogs. Based on multilevel multivariable logistic regression, a risk factor for the shedding of generic E. coli resistant to ampicillin was attending dog day care. Risk factors for the shedding of E. coli resistant to at least one anti-microbial included attending dog day care and being a large mixed breed dog, whereas consumption of commercial dry and home cooked diets was protective factor. In a multilevel multivariable model for the shedding of multiclass-resistant E. coli, exposure to compost and being a large mixed breed dog were risk factors, while consumption of a commercial dry diet was a sparing factor. Pet dogs are a potential reservoir of anti-microbial-resistant generic E. coli; some dog characteristics and management factors are associated with the prevalence of anti

Acceptability and confidence in antiretroviral generics of physicians and HIV-infected patients in France.

Science.gov (United States)

Allavena, Clotilde; Jacomet, Christine; Pereira, Bruno; Morand-Joubert, Laurence; Bagheri, Haleh; Cotte, Laurent; Garaffo, Rodolphe; Gerbaud, Laurent; Dellamonica, Pierre

2014-01-01

Switching brand name medications to generics is recommended in France in the interest of cost effectiveness but patients and physicians are sometimes not convinced that switching is appropriate. Some antiretroviral (ARV) generics (ZDV, 3TC, NVP) have been marketed in France since 2013. A multicentric cross-sectional survey was performed in September 2013 to evaluate the perception of generics overall and ARV generics in physicians and HIV-infected patients and factors associated to their acceptability. Adult HIV outpatients were asked to complete a self-questionnaire on their perception of generics. Physicians completed a questionnaire on the acceptability of generics and ARV generics. Socio-demographic data, medical history and HIV history were collected. 116 physicians in 33 clinics (68% in University Hospital) included 556 patients (France-native 77%, active employment 59%, covered by social Insurance 100%, homosexual/bisexual contamination 47%, median HIV duration 13 years, hepatitis coinfection 16%, on ARV therapy 95%). Overall, patients accepted and had confidence in generics in 76% and 55% of the cases, respectively. Switching ARVs for generics was accepted by 44% of the patients but only by 17% if the pill burden was going to increase. 75% of the physicians would prescribe generics, but this decreased to only 26% if the combo had to be broken. The main reasons for non-prescription of generics were previous brand name ARV-induced side effects (35%), refusal of generics overall (37%), lack of understanding of generics (26%), risk of non-observance of treatment (44%), anxiety (47%) and depressive symptoms (25%). In multivariate analysis, factors associated with the acceptability of ARV generics in patients were the use of generics overall (p<0.001) and in physicians, the absence of concern regarding the drug efficacy (p<0.001) and being aware that the patient would accept generics overall (p=0.03) and ARV generics (p=0.04). No factors related to

Introduction of developing a list of MSO generic scenarios for PHWR

Energy Technology Data Exchange (ETDEWEB)

Park, Jae Wan; Park, Jun Hyun; Bae, Hui Soo [STANDARD Testing and Engineering Ing. Ltd, Daejeon (Korea, Republic of)

2016-10-15

Multiple Spurious Operation(MSO) scenarios should contain scenarios threatening Post-fire safe shutdown function by MSO of Safe Shutdown Equipments(SSEs) as well as Non-SSEs. The list of MSO generic scenarios(NEI 00-01, Appendix G) was developed by industrial survey. Although not all scenarios of the list of MSO generic scenarios(NEI 00-01, Appendix G) are considered applicable to every reactor type, this list provides an input about MSO identification and treatment process. If NEI 00-01 is applied to other reactor type, analyst should review applicability of the list of generic scenarios(NEI 00-01, Appendix G) and consider potential MSO scenarios undescribed in the list of MSO generic scenarios(NEI 00-01, Appendix G). Especially, in PHWR case, there is no list of MSO generic scenarios in Canada or internationally. There are substantial physical variations between NPPs. So some generic scenarios(NEI 00-01, Appendix G) would need validation. Nevertheless, industrial stakeholder have not did any MSO work until now. In this paper, results of first stage research that develop the list of MSO generic scenarios for pressurized heavy water reactor(PHWR) is introduced. According to the review results, specific review of the list of MSO generic scenarios(NEI 00-01, Appendix G) is required such as how it applies to PHWR. And criteria was established for review of availability of the list of generic scenarios(NEI 00-01, Appendix G). However there are still many tasks such as potential scenario review, risk model review and expert panel review.

Design of generic coal conversion facilities: Indirect coal liquefaction, Fischer-Tropsch synthesis

Energy Technology Data Exchange (ETDEWEB)

1991-10-01

A comprehensive review of Fischer-Tropsch (F-T) technology, including fixed, fluidized, and bubble column reactors, was undertaken in order to develop an information base before initiating the design of the Fischer-Tropsch indirect liquefaction PDU as a part of the Generic Coal Conversion Facilities to be built at the Pittsburgh Energy Technology Center (PETC). The pilot plant will include a fixed bed and slurry bubble column reactor for the F-T mode of operation. The review encompasses current status of both these technologies, their key variables, catalyst development, future directions, and potential improvement areas. However, more emphasis has been placed on the slurry bubble column reactor since this route is likely to be the preferred technology for commercialization, offering process advantages and, therefore, better economics than fixed and fluidized bed approaches.

Astaxanthin-producing green microalga Haematococcus pluvialis: from single cell to high value commercial products

Directory of Open Access Journals (Sweden)

Md. Mahfuzur Rahman Shah

2016-04-01

Full Text Available Many species of microalgae have been used as source of nutrient rich food, feed and health promoting compounds. Among the commercially important microalgae, Haematococcus pluvialis is the richest source of natural astaxanthin which is considered as super anti-oxidant. Natural astaxanthin produced by H. pluvialis has significantly greater antioxidant capacity than the synthetic one. Astaxanthin has important applications in the nutraceuticals, cosmetics, food, and aquaculture industries. Thanks to many researches it is now evident, that astaxanthin can significantly reduce free radicals and oxidative stress and help human body maintain a healthy state. With extraordinary potency and increase in demand, astaxanthin is one of the high-value microalgal products of the future. Thus, this comprehensive review summarizes the most important aspects of the biology, biochemical composition, biosynthesis and astaxanthin accumulation in the cells of H. pluvialis and its wide range of applications for humans and animals. In this paper, important and recent developments ranging from cultivation, harvest and postharvest bio-processing technologies to metabolic control and genetic engineering are reviewed in detail, focusing on biomass and astaxanthin production from this biotechnologically important microalga. Simultaneously, critical bottlenecks and major challenges in commercial scale production; current and prospective global market of H. pluvialis derived astaxanthin are also presented in a critical manner. A new biorefinery concept for H. pluvialis has been also suggested to guide towards economically sustainable approach for microalgae cultivation and processing. This report could serve as a useful guide to present current status of knowledge in the field and highlight key areas for future development of H. pluvialis astaxanthin technology and its large scale commercial implementation.

Frequency and Informativeness of Gestural Cues Accompanying Generic and Particular Reference

Science.gov (United States)

Meyer, Meredith; Gelman, Susan A.; Stilwell, Sarah M.

2015-01-01

Generic noun phrases, or generics, refer to abstract categories ("Dogs" bark) rather than particular individuals ("Those dogs" bark). Study 1 investigated how parents use gestures in association with generic versus particular reference during naturalistic interactions with their 2- and 3-year-old children. Parents provided…

A GENERIC PACKAGING TECHNIQUE USING FLUIDIC ISOLATION FOR LOW-DRIFT IMPLANTABLE PRESSURE SENSORS.

Science.gov (United States)

Kim, A; Powell, C R; Ziaie, B

2015-06-01

This paper reports on a generic packaging method for reducing drift in implantable pressure sensors. The described technique uses fluidic isolation by encasing the pressure sensor in a liquid-filled medical-grade polyurethane balloon; thus, isolating it from surrounding aqueous environment that is the major source of baseline drift. In-vitro tests using commercial micromachined piezoresistive pressure sensors show an average baseline drift of 0.006 cmH 2 O/day (0.13 mmHg/month) for over 100 days of saline soak test, as compared to 0.101 cmH 2 O/day (2.23 mmHg/month) for a non-fluidic-isolated one soaked for 18 days. To our knowledge, this is the lowest reported drift for an implantable pressure sensor.

An audit of generic prescribing in a general surgical department.

LENUS (Irish Health Repository)

Gleeson, M

2013-01-17

BACKGROUND: The Health Service Executive introduced a generic prescription policy to reduce costs. Despite this, generic prescription rates remain low. AIM: To audit in-patient prescription practice in a single surgical department and identify potential savings which could be realised by adherence to the generic prescribing policy. METHODS: Surgical in-patient charts were obtained at the point of discharge and their drug prescription information was recorded. RESULTS: 51 % of prescriptions involved a trade-name prescription where an appropriate generic equivalent existed. The cost implications for hospital and community patients were found to be greatly affected by substitution policies that exist at hospital pharmacy level. CONCLUSION: There is a need to promote greater adherence to generic prescribing amongst hospital doctors in line with international best practice. It can have a positive impact in terms of safe prescribing and can have cost implications at both hospital and community level.

A fast and systematic procedure to develop dynamic models of bioprocesses: application to microalgae cultures

Directory of Open Access Journals (Sweden)

J. Mailier

2010-09-01

Full Text Available The purpose of this paper is to report on the development of a procedure for inferring black-box, yet biologically interpretable, dynamic models of bioprocesses based on sets of measurements of a few external components (biomass, substrates, and products of interest. The procedure has three main steps: (a the determination of the number of macroscopic biological reactions linking the measured components; (b the estimation of a first reaction scheme, which has interesting mathematical properties, but might lack a biological interpretation; and (c the "projection" (or transformation of this reaction scheme onto a biologically-consistent scheme. The advantage of the method is that it allows the fast prototyping of models for the culture of microorganisms that are not well documented. The good performance of the third step of the method is demonstrated by application to an example of microalgal culture.

Exploring community pharmacists' views on generic medicines: a nationwide study from Malaysia.

Science.gov (United States)

Chong, Chee Ping; Hassali, Mohamed Azmi; Bahari, Mohd Baidi; Shafie, Asrul Akmal

2011-02-01

To evaluate the Malaysian community pharmacists' views on generic medicines. A sample of 1419 Malaysian community pharmacies with resident pharmacists. A cross-sectional nationwide survey using a self-completed mailing questionnaire. Pharmacists' views on generic medicines including issues surrounding efficacy, safety, quality and bioequivalence. Responses were received from 219 pharmacies (response rate 15.4%). Only 50.2% of the surveyed pharmacists agreed that all products that are approved as generic equivalents can be considered therapeutically equivalent with the innovator medicines. Around 76% of respondents indicated that generic substitution of narrow therapeutic index medicines is inappropriate. The majority of the pharmacists understood that a generic medicine must contain the same amount of active ingredient (84.5%) and must be in the same dosage form as the innovator brand (71.7%). About 21% of respondents though that generic medicines are of inferior quality compared to innovator medicines. Most of the pharmacists (61.6%) disagreed that generic medicines produce more side-effects than innovator brand. Pharmacists graduated from Malaysian universities, twinning program and overseas universities were not differed significantly in their views on generic medicines. Additionally, the respondents appeared to have difficulty in ascertaining the bioequivalent status of the marketed generic products in Malaysia. The Malaysian pharmacists' have lack of information and/or trust in the generic manufacturing and/or approval system in Malaysia. This issue should be addressed by pharmacy educators and relevant government agencies.

Contribution to draft generic environmental impact statement on commercial waste management: radioactive waste isolation in geologic formations

International Nuclear Information System (INIS)

1978-04-01

This document concentrates on deep geologic isolation of wastes in bedded salt, granite, shale, and basalt with emphasis on wastes from three fuel cycles: reprocessing wastes from uranium and plutonium recycling, reprocessing wastes from uranium-only recycling, and spent unreprocessed fuel with no recycling. The analyses presented in this document are based on preconceptual repository designs. As the repository designs progress through future phases, refinements will occur which might modify some of these results. The 12 sections in the report are: introduction; selection and description of generic repository sites; LWR wastes to be isolated in geologic formations; description of waste isolation facilities; effluents from the waste isolation facility; assessment of environment impacts for various geographical locations of a waste isolation facility; environmental monitoring; decommissioning; mine decommissioning site restoration; deep geologic alternative actions; potential mechanisms of containment failure; and considerations relevant to provisional versus final storage

A generic coding approach for the examination of meal patterns.

Science.gov (United States)

Woolhead, Clara; Gibney, Michael J; Walsh, Marianne C; Brennan, Lorraine; Gibney, Eileen R

2015-08-01

Meal pattern analysis can be complex because of the large variability in meal consumption. The use of aggregated, generic meal data may address some of these issues. The objective was to develop a meal coding system and use it to explore meal patterns. Dietary data were used from the National Adult Nutrition Survey (2008-2010), which collected 4-d food diary information from 1500 healthy adults. Self-recorded meal types were listed for each food item. Common food group combinations were identified to generate a number of generic meals for each meal type: breakfast, light meals, main meals, snacks, and beverages. Mean nutritional compositions of the generic meals were determined and substituted into the data set to produce a generic meal data set. Statistical comparisons were performed against the original National Adult Nutrition Survey data. Principal component analysis was carried out by using these generic meals to identify meal patterns. A total of 21,948 individual meals were reduced to 63 generic meals. Good agreement was seen for nutritional comparisons (original compared with generic data sets mean ± SD), such as fat (75.7 ± 29.4 and 71.7 ± 12.9 g, respectively, P = 0.243) and protein (83.3 ± 26.9 and 80.1 ± 13.4 g, respectively, P = 0.525). Similarly, Bland-Altman plots demonstrated good agreement (<5% outside limits of agreement) for many nutrients, including protein, saturated fat, and polyunsaturated fat. Twelve meal types were identified from the principal component analysis ranging in meal-type inclusion/exclusion, varying in energy-dense meals, and differing in the constituents of the meals. A novel meal coding system was developed; dietary intake data were recoded by using generic meal consumption data. Analysis revealed that the generic meal coding system may be appropriate when examining nutrient intakes in the population. Furthermore, such a coding system was shown to be suitable for use in determining meal-based dietary patterns. © 2015

Pointing As a Socio-Pragmatic Cue to Particular vs.Generic Reference

Science.gov (United States)

Meyer, Meredith; Baldwin, Dare A.

2013-01-01

Generic noun phrases, or generics, refer to abstract kind categories ("Dogs" bark) rather than particular individuals ("Those dogs" bark). How do children distinguish these distinct kinds of reference? We examined the role of one socio-pragmatic cue, namely pointing, in producing and comprehending generic versus particular…

[Users sceptical about generic drugs: an anthropological approach].

Science.gov (United States)

Sarradon-Eck, A; Blanc, M-A; Faure, M

2007-06-01

Since the enactment of the 2002 legislative measures favoring the prescription of generic drugs, various quantitative studies have shown that approval by prescribers and users has risen in France. Nevertheless, scepticism remains as well as distrust towards these drugs focusing on their effectiveness compared with brand-name drugs, on potential dangers, and on the interruption they cause in prescription and consumption habits. Using a comprehensive approach, this article analyzes the social and cultural logic behind the negative image of generic drugs. The materials issued from an ethnographic study on the prescription of drugs for high blood pressure. Sixty-eight interviews were undertaken between April 2002 and October 2004 with people (39 women and 29 men, between the age of 40 and 95, 52 over the age of 60) treated for over a year for high blood pressure in rural areas in the Southeast of France. Thirteen people provided unsolicited opinions about generic drugs. Analysis of the information collected shows that users have various representations of generic drugs, including the idea of counterfeited and foreign drugs. These representations interfere with the adjustment process and the development of consumer loyalty. They are part of a set of social representations about drugs which form and express the user's reality. In these representations, the drug is an ambivalent object, carrier of both biological effectiveness and toxicity; it is also the metonymical extension of the prescriber, bestowing upon the prescription a symbolic value. By placing the generic drug in its network of symbolic and social meaning, this study highlights the coherence of the scepticism towards generic drugs by consumers (and prescribers) with a system of common opinion in which drugs are everyday things, personalized and compatible with users, symbolic exchange carriers in the physician-patient relationship, and in which confidence in the drug is also that given to the health care

An evaluation of consumers' knowledge, perceptions and attitudes regarding generic medicines in Auckland.

Science.gov (United States)

Babar, Zaheer-Ud-Din; Stewart, Joanna; Reddy, Shiwangni; Alzaher, Woroud; Vareed, Prateeka; Yacoub, Nineweh; Dhroptee, Bandhana; Rew, Anne

2010-08-01

The aim of this project was to evaluate the perceptions, knowledge and attitudes regarding generic medicines. A cross-sectional study, with self administered questionnaires, was conducted to survey consumers visiting pharmacies in four regions of Auckland (North Shore, Waitakere, Central Auckland and South Auckland). Through stratified random sampling, approximately 10% of pharmacies from each region were selected, which turn out to be 30 pharmacies. Every alternate customer coming to the pharmacy, who was eligible to participate in the study, was asked by the researchers to complete the questionnaire. A total of 441 questionnaires were included in the analysis. Different response rates were obtained in different regions of Auckland. Of all respondents, 51.6% had previous knowledge of generic medicines. Pharmacists were the main source of information regarding generic medicines followed by doctors and media. A higher level of education had a direct relationship with having correct knowledge of generics (P = .002). Attitude of participants toward the use of generic medicines was determined by their knowledge of generics, whether it was recommended by a pharmacist and their type of illness. Participants were more prepared to change to a generic for a minor illness (79%) than for a major illness (58.7%). Those who had better knowledge were more likely than those with poor knowledge to say they would to use a generic in major illness (P = .001) as well as minor illness (P < .0001). Previous positive experiences with generics also determined consumers' willingness to use generics. Many consumers have misconceptions regarding generic medicines. Having knowledge about generics and the advice by doctors and pharmacists are key indicators to improve the quality use of generic medicines.

Patients' concern about their medicine after a generic switch

DEFF Research Database (Denmark)

Østergaard Rathe, Jette; Søndergaard, Jens; Jarbøl, Dorte E

2014-01-01

PURPOSE: This study aims to investigate the possible association between patients' concerns about their medicine and generic switch. METHODS: Cross-sectional survey was carried out comprising responses from 2217 randomly selected persons aged 20 years or older and living in the Region of Southern...... Denmark, who had redeemed generically substitutable drugs in September 2008. For each patient, we focused on the purchase of one generically substitutable drug (index drug). We applied the specific concerns subscale from the Beliefs about Medicine Questionnaire (BMQ) to analyse lack of confidence....... RESULTS: No statistically significant associations were found between concerns about the index medicine and the generic switch (-0.02 95% CI: -0.10; 0.05). Viewing medicines as harmful in general was associated with increased concerns (BMQ general harm: 0.39 95% CI: 0.30; 0.47 and BMQ general overuse: 0...

Generic Drugs: Questions and Answers

Science.gov (United States)

... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Drugs Home Drugs Resources for You Information for Consumers (Drugs) Questions & Answers Generic Drugs: Questions & Answers Share Tweet Linkedin Pin it More ...

A Domain-Specific Language for Generic Interlocking Models and Their Properties

DEFF Research Database (Denmark)

Vu, Linh Hong; Haxthausen, Anne Elisabeth; Peleska, Jan

2017-01-01

of this work is to provide a domain-specific language for generic models and an instantiator tool taking not only configuration data but also a generic model as input instead of using a hard-coded generator for instantiating only one fixed generic model and its properties with configuration data....

Bioequivalence and in vitro antimicrobial activity between generic and brand-name levofloxacin.

Science.gov (United States)

Sun, Hsin-Yun; Liao, Hsiao-Wei; Sheng, Meng-Huei; Tai, Hui-Min; Kuo, Ching-Hua; Sheng, Wang-Huei

2016-07-01

Generic agents play a crucial role in reducing the cost of medical care in many countries. However, the therapeutic equivalence remains a great concern. Our study aims to assess the in vitro antimicrobial activity and bioequivalence between generic and brand-name levofloxacin. Enantiomeric purity test, dissolution test, and in vitro antimicrobial susceptibility against seven clinically important pathogens by the agar dilution method were employed to assess the similarity between four generic products and brand-name levofloxacin (Daiichi Sankyo). All the generic and brand-name levofloxacin passed enantiomeric purity test. The results of dissolution tests were not similar among the generic products and the brand-name levofloxacin. Compared with the generic products, the brand-name levofloxacin had the smallest mean variations (-25% to 13%) with reference standard (United States Pharmacopeia levofloxacin Reference Standards). Variations were observed particularly in dissolution profiles and in vitro activity between generic products and brand-name levofloxacin. Copyright © 2016 Elsevier Inc. All rights reserved.

Increased Topical Generic Prices by Manufacturers: An Isolated Trend or Worrisome Future?

Science.gov (United States)

Bhatt, Mehul D; Bhatt, Birju D; Dorrian, James T; McLellan, Beth N

2018-03-12

There is limited data regarding generic medication prices. Recent studies have shown price changes at the retail level, but much is not known about the pharmaceutical supply chain or price changes at the manufacturer level. We sought to examine the extent of price changes for topical generic medications. A comprehensive review of average wholesale prices (AWP) and manufacturers of topical generics and available corresponding branded medications was conducted for 2005 and 2016. A total of 51 topical chemical entities were examined. Between 2005 and 2016, the AWP of topical generics increased by 273% and the AWP of topical branded increased by 379%. The topical generic with the most price change increased by 2529%. Eight of the top twenty topical generics with the highest increase in AWP also had an increase in the number of manufacturers. These findings are not generalizable to medications used in other areas of medicine CONCLUSIONS: Topical generic prices are rapidly increasing at the manufacturer level. Copyright © 2018. Published by Elsevier Inc.

Optimising the design and operation of semi-continuous affinity chromatography for clinical and commercial manufacture.

Science.gov (United States)

Pollock, James; Bolton, Glen; Coffman, Jon; Ho, Sa V; Bracewell, Daniel G; Farid, Suzanne S

2013-04-05

This paper presents an integrated experimental and modelling approach to evaluate the potential of semi-continuous chromatography for the capture of monoclonal antibodies (mAb) in clinical and commercial manufacture. Small-scale single-column experimental breakthrough studies were used to derive design equations for the semi-continuous affinity chromatography system. Verification runs with the semi-continuous 3-column and 4-column periodic counter current (PCC) chromatography system indicated the robustness of the design approach. The product quality profiles and step yields (after wash step optimisation) achieved were comparable to the standard batch process. The experimentally-derived design equations were incorporated into a decisional tool comprising dynamic simulation, process economics and sizing optimisation. The decisional tool was used to evaluate the economic and operational feasibility of whole mAb bioprocesses employing PCC affinity capture chromatography versus standard batch chromatography across a product's lifecycle from clinical to commercial manufacture. The tool predicted that PCC capture chromatography would offer more significant savings in direct costs for early-stage clinical manufacture (proof-of-concept) (∼30%) than for late-stage clinical (∼10-15%) or commercial (∼5%) manufacture. The evaluation also highlighted the potential facility fit issues that could arise with a capture resin (MabSelect) that experiences losses in binding capacity when operated in continuous mode over lengthy commercial campaigns. Consequently, the analysis explored the scenario of adopting the PCC system for clinical manufacture and switching to the standard batch process following product launch. The tool determined the PCC system design required to operate at commercial scale without facility fit issues and with similar costs to the standard batch process whilst pursuing a process change application. A retrofitting analysis established that the direct cost

Generic policy in Bulgaria: a policy of failure or success?

Directory of Open Access Journals (Sweden)

Assena Stoimenova

2016-09-01

Full Text Available Generic medicines play a key role in managing the financial resources for pharmaceuticals in every country. This study analysed the generic policy legislative framework in Bulgaria with the aim to identify whether the policy implementation can be considered successful in the light of an international review of such policies introduced in other countries, or on the contrary, it has failed to deliver the main benefits. Legislative analysis, desktop study and macroeconomic overview of the Bulgarian pharmaceutical market were included. The study showed that only 3 out of 11 important policy elements are implemented in the country. Bulgaria has one of the highest shares of generics, an average of 81.39% (volume, for the studied period (2006–2014. However, further research is needed to evaluate the success of the existing generic policy in Bulgaria, as the market share of generic drugs is not the only measure of the policy efficiency.

The Impact of Information on Doctors’ Attitudes Toward Generic Drugs

Directory of Open Access Journals (Sweden)

Aggeliki V. Tsaprantzi MD

2016-03-01

Full Text Available The objective of this study is to assess the impact of information on doctors’ attitudes and perceptions toward generics. A cross-sectional survey based on a specially designed 21-item questionnaire was conducted. The survey involved doctors of different specialties working in a public hospital in Greece. The analysis includes descriptive and inferential statistics, reliability and validity tests, as well as structural equation modeling to evaluate the causal model. Statistical analysis was accomplished by using SPSS 20 and Amos 20. A total of 134 questionnaires out of 162 were received, providing a response rate of 82.71%. A number of significant associations were found between information and perceptions about generic medicines with demographic characteristics. It seems that the provision of quality information on generic drugs influences doctors’ attitudes and prescription practices toward generic drugs. This is not a static process but a rather dynamic issue involving information provision policies for strengthening the proper doctors’ attitudes toward generic drugs.

Guide for generic application of Reliability Centered Maintenance (RCM) recommendations

International Nuclear Information System (INIS)

Schwan, C.A.; Toomey, G.E.; Morgan, T.A.; Darling, S.S.

1991-02-01

Previously completed reliability centered maintenance (RCM) studies form the basis for developing or refining a preventive maintenance program. This report describes a generic methodology that will help utilities optimize nuclear plant maintenance programs using RCM techniques. This guide addresses the following areas: history of the generic methodology development process, and use of the generic methodology for conducting system-to-system and component-to-component evaluations. 2 refs., 2 figs., 5 tabs

When Does an Argument Use a Generic Example?

Science.gov (United States)

Yopp, David A.; Ely, Rob

2016-01-01

We offer criteria that an observer can use to determine whether an argument that uses an example to argue for a general claim appeals to that example generically. We review existing literature on generic example and note the strengths of each contribution, as well as inconsistencies among uses of the term. We offer several examples from the…

The generics in transplantation and the rules on their use.

Science.gov (United States)

Masri, Marwan

2003-06-01

By definition a product identified by its official chemical name rather than an advertised brand name is called a generic. If a drug exert its pharmacological effects at the same site, have the same potency, same dosage form and same bioavailability as a brand name, reference listed drug (RLD), is considered as a generic. However inactive ingredients can differ between brand name and generic. It is through the regulations of the FDA that the generics gained many ground in the drug market, they currently account to more than 42% of the total prescription in the USA. These regulations include the abbreviated new drug application (ANDA) for the registration process and drug substitution at the pharmacy level without patient or physician consent. This coupled with a keen interest of third party payers and the health authorities to reduce the high transplant health budget (over 2 Billion US $) made it a necessity to introduce the generics into the field of transplantation. Using the above mentioned definition we can theoretically say that all anti-lymphocytes, produced in the same animal species, are generic of each. Moreover, monoclonal antibodies that are directed against the same target and have the same bioavailability are also consider generics to each other. Of all the immunosuppressive drugs that have been introduced into the field of transplantation none has been as dominant as Cyclosporine. Cyclosporine became and still is the backbone for any immunosuppressive protocol. In the year 1992, Consupren, the first, non-FDA approved, generic to Sandimmun was introduced. Although Consupren was not bioequivalent to Neoral, however, long-term results in kidney transplantation have been similar for both drugs. The introduction of Consupren resulted in a near 40% reduction in the total cost of immunosuppressive therapy. Interestingly the cost of the brand name drug Neoral was also reduced by 20%. The cost reduction allowed the introduction of the new immunosuppressive

The SENSEI Generic In Situ Interface

Energy Technology Data Exchange (ETDEWEB)

Ayachit, Utkarsh [Kitware, Inc., Clifton Park, NY (United States); Whitlock, Brad [Intelligent Light, Rutherford, NJ (United States); Wolf, Matthew [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Loring, Burlen [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Geveci, Berk [Kitware, Inc., Clifton Park, NY (United States); Lonie, David [Kitware, Inc., Clifton Park, NY (United States); Bethel, E. Wes [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2017-04-11

The SENSEI generic in situ interface is an API that promotes code portability and reusability. From the simulation view, a developer can instrument their code with the SENSEI API and then make make use of any number of in situ infrastructures. From the method view, a developer can write an in situ method using the SENSEI API, then expect it to run in any number of in situ infrastructures, or be invoked directly from a simulation code, with little or no modification. This paper presents the design principles underlying the SENSEI generic interface, along with some simplified coding examples.

Comparison of Outcomes Following a Switch From a Brand to an Authorized Versus Independent Generic Drug.

Science.gov (United States)

Hansen, R A; Qian, J; Berg, R L; Linneman, J G; Seoane-Vazquez, E; Dutcher, S; Raofi, S; Page, C D; Peissig, P L

2018-02-01

Authorized generics are identical in formulation to brand drugs, manufactured by the brand company but marketed as a generic. Generics, marketed by generic manufacturers, are required to demonstrate pharmaceutical and bioequivalence to the brand drug, but repetition of clinical trials is not required. This retrospective cohort study compared outcomes for generics and authorized generics, which serves as a generic vs. brand proxy that minimizes bias against generics. For the seven drugs studied between 1999 and 2014, 5,234 unique patients were on brand drugs prior to generic entry and 4,900 (93.6%) switched to a generic. During the 12 months following the brand-to-generic switch, patients using generics vs. authorized generics were similar in terms of outpatient visits, urgent care visits, hospitalizations, and medication discontinuation. The likelihood of emergency department (ED) visits was slightly higher for authorized generics compared with generics. These data suggest that generics were clinically no worse than their proxy brand comparators. © 2017 American Society for Clinical Pharmacology and Therapeutics.

40 CFR 721.10146 - Partially fluorinated condensation polymer (generic).

Science.gov (United States)

2010-07-01

... polymer (generic). 721.10146 Section 721.10146 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10146 Partially fluorinated condensation polymer (generic). (a) Chemical... as partially fluorinated condensation polymer (PMN P-07-87) is subject to reporting under this...

40 CFR 721.10151 - Modified styrene, divinylbenzene polymer (generic).

Science.gov (United States)

2010-07-01

... polymer (generic). 721.10151 Section 721.10151 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10151 Modified styrene, divinylbenzene polymer (generic). (a) Chemical... as modified styrene, divinylbenzene polymer (PMN P-07-642) is subject to reporting under this section...

Generic task problem descriptions: Category B, C, and D tasks

International Nuclear Information System (INIS)

1978-06-01

This document contains information relating to Category B, C, and D generic technical activities. The specific information provided for each task includes the reactor type to which the generic issue applies, the NRC division with lead responsibility and a description of the problem to be addressed by the task. Also provided in this document is a listing of Category A generic technical activities and definitions of Priority Categories A, B, C, and D

Treatment of supermarket vegetable wastes to be used as alternative substrates in bioprocesses.

Science.gov (United States)

Díaz, Ana Isabel; Laca, Amanda; Laca, Adriana; Díaz, Mario

2017-09-01

Fruits and vegetables have the highest wastage rates at retail and consumer levels. These wastes have promising potential for being used as substrates in bioprocesses. However, an effective hydrolysis of carbohydrates that form these residues has to be developed before the biotransformation. In this work, vegetable wastes from supermarket (tomatoes, green peppers and potatoes) have been separately treated by acid, thermal and enzymatic hydrolysis processes in order to maximise the concentration of fermentable sugars in the final broth. For all substrates, thermal and enzymatic processes have shown to be the most effective. A new combined hydrolysis procedure including these both treatments was also assayed and the enzymatic step was successfully modelled. With this combined hydrolysis, the percentage of reducing sugars extracted was increased, in comparison with the amount extracted from non-hydrolysed samples, approximately by 30% in the case of tomato and green peeper wastes. For potato wastes this percentage increased from values lower than 1% to 77%. In addition, very low values of fermentation inhibitors were found in the final broth. Copyright © 2017. Published by Elsevier Ltd.

Factors influencing the preference for purchasing generic drugs in a Southern Brazilian city.

Science.gov (United States)

Guttier, Marília Cruz; Silveira, Marysabel Pinto Telis; Luiza, Vera Lucia; Bertoldi, Andréa Dâmaso

2017-06-26

The objective of this study is to identify factors associated with the preference for purchasing generic drugs in a medium-sized municipality in Southern Brazil. We have analyzed data from a population-based cross-sectional study conducted in 2012 with a sample of 2,856 adults (≥ 20 years old). The preference for purchasing generic drugs was the main outcome. The explanatory variables were the demographic and socioeconomic variables. Statistical analyses included Poisson regressions. The preference for purchasing generic drugs was 63.2% (95%CI 61.4-64.9). The variables correlated with this preference in the fully adjusted models were: male (prevalence ratio [PR] = 1.08; 95%CI 1.03-1.14), age of 20-39 years (PR = 1.10; 95%CI 1.02-1.20), low socioeconomic status (PR = 1.15; 95%CI 1.03-1.28), and good knowledge about generic drugs (PR= 4.66; 95%CI 2.89-7.52). Among those who preferred to purchase generic drugs, 55.1% have reported accepting to replace the prescribed drug (if not a generic) with the equivalent generic drug. Another correlate of the preference for purchasing generic drugs was because individuals consider their quality equivalent to reference medicines (PR = 2.15; 95%CI 1.93-2.41). Knowledge about generic drugs was the main correlate of the preference for purchasing generic drugs. The greater the knowledge or positive perception about generic drugs, the greater is the preference to purchase them. Therefore, educational campaigns for healthcare professionals and consumers appear to be the best strategy for expanding the use of generic drugs in Brazil.

Analysis of Knowledge Level and Perception on Singkawang City Community towards Generic Medicines

Directory of Open Access Journals (Sweden)

Forid Morison

2015-03-01

Full Text Available Survey data show that the use of generic medicines in Indonesia is relatively very small, which only amounted 7%. This is due to lack of knowledge and poor perceptions towards generic medicines. Knowledge level and perceptions towards generic medicines are inflenced by community characteristics and information resource regarding generic medicines. The aim of this study was to determine the association between community characteristic and information resources with knowledge level and perception towards generic medicines. This study was an analytical survey with cross-sectional descriptive approach on 142 selected respondents who were fulfi inclusion and exclusion criteria. This study was conducted in June 2014 at several randomly selected locations on Singkawang City. The study show that 76 respondents (53.5% had inadequate knowledge and 123 respondents (86.6% had a good perception towards generic medicines. There is signifiant relationship between ethnicity (p=0.000 and information resources (p=0.009 with knowledge level regarding generic medicines at signifiance level of p<0.05. Although good perceptions were noted among the respondents, widespread dissemination of information regarding generic medicines should be continued to increase generic medicines used.

Developing a mesophilic co-culture for direct conversion of cellulose to butanol in consolidated bioprocess.

Science.gov (United States)

Wang, Zhenyu; Cao, Guangli; Zheng, Ju; Fu, Defeng; Song, Jinzhu; Zhang, Junzheng; Zhao, Lei; Yang, Qian

2015-01-01

Consolidated bioprocessing (CBP) of butanol production from cellulosic biomass is a promising strategy for cost saving compared to other processes featuring dedicated cellulase production. CBP requires microbial strains capable of hydrolyzing biomass with enzymes produced on its own with high rate and high conversion and simultaneously produce a desired product at high yield. However, current reported butanol-producing candidates are unable to utilize cellulose as a sole carbon source and energy source. Consequently, developing a co-culture system using different microorganisms by taking advantage of their specific metabolic capacities to produce butanol directly from cellulose in consolidated bioprocess is of great interest. This study was mainly undertaken to find complementary organisms to the butanol producer that allow simultaneous saccharification and fermentation of cellulose to butanol in their co-culture under mesophilic condition. Accordingly, a highly efficient and stable consortium N3 on cellulose degradation was first developed by multiple subcultures. Subsequently, the functional microorganisms with 16S rRNA sequences identical to the denaturing gradient gel electrophoresis (DGGE) profile were isolated from consortium N3. The isolate Clostridium celevecrescens N3-2 exhibited higher cellulose-degrading capability was thus chosen as the partner strain for butanol production with Clostridium acetobutylicum ATCC824. Meanwhile, the established stable consortium N3 was also investigated to produce butanol by co-culturing with C. acetobutylicum ATCC824. Butanol was produced from cellulose when C. acetobutylicum ATCC824 was co-cultured with either consortium N3 or C. celevecrescens N3-2. Co-culturing C. acetobutylicum ATCC824 with the stable consortium N3 resulted in a relatively higher butanol concentration, 3.73 g/L, and higher production yield, 0.145 g/g of glucose equivalent. The newly isolated microbial consortium N3 and strain C. celevecrescens N3

77 FR 60125 - Generic Drug Facilities, Sites and Organizations

Science.gov (United States)

2012-10-02

...] Generic Drug Facilities, Sites and Organizations AGENCY: Food and Drug Administration, HHS. ACTION: Notice..., and certain sites and organizations identified in a generic drug submission, that they must provide... and Innovation Act (FDASIA). This notice is intended to help organizations ascertain if they need to...

Comparison of Generic Drug Reviews for Marketing Authorization between Japan and Canada.

Science.gov (United States)

Kuribayashi, Ryosuke; Appleton, Scott

2017-09-01

Generic drugs are assuming an increasingly important role in sustaining modern healthcare systems, as the cost of healthcare, including drug usage, is gradually expanding around the world. To date, published articles comparing generic drug reviews between different countries are scarce. The objective of this study was to examine generic drug reviews in Japan and Canada. We surveyed generic drug reviews from Japan and Canada and compared the following points: general matter (application types, type of partial change or Supplement to an Abbreviated New Drug Submission, application and approval numbers, review period, application format, review report, responsibility for review), bioequivalence studies for solid oral dosage forms, and bioequivalence guidelines, guidance, or basic principles regarding various dosage forms. This survey described the many similarities and differences in generic drug reviews between the two countries and points that should be improved to promote better generic drug reviews. In particular, regulations for the definition of the same or different active pharmaceutical ingredients (APIs) are similar for both authorities. The results clarified the future challenges of generic drug reviews, and the differences highlighted by this survey will be important considerations for the future. This is the first article to present and discuss the details of generic drug reviews between Japan and Canada.

Avoidance of generic competition by Abbott Laboratories' fenofibrate franchise.

Science.gov (United States)

Downing, Nicholas S; Ross, Joseph S; Jackevicius, Cynthia A; Krumholz, Harlan M

2012-05-14

The ongoing debate concerning the efficacy of fenofibrate has overshadowed an important aspect of the drug's history: Abbott Laboratories, the maker of branded fenofibrate, has produced several bioequivalent reformulations that dominate the market, although generic fenofibrate has been available for almost a decade. This continued use of branded formulations, which cost twice as much as generic versions of fenofibrate, imposes an annual cost of approximately $700 million on the US health care system. Abbott Laboratories maintained its dominance of the fenofibrate market in part through a complex switching strategy involving the sequential launch of branded reformulations that had not been shown to be superior to the first-generation product and patent litigation that delayed the approval of generic formulations. The small differences in dose of the newer branded formulations prevented their substitution with generics of older-generation products. As soon as direct generic competition seemed likely at the new dose level, where substitution would be allowed, Abbott would launch another reformulation, and the cycle would repeat. Based on the fenofibrate example, our objective is to describe how current policy can allow pharmaceutical companies to maintain market share using reformulations of branded medications, without demonstrating the superiority of next-generation products.

Generic legislation of new psychoactive drugs.

Science.gov (United States)

van Amsterdam, Jan; Nutt, David; van den Brink, Wim

2013-03-01

New psychoactive drugs (NPDs, new psychoactive substances) enter the market all the time. However, it takes several months to ban these NPDs and immediate action is generally not possible. Several European countries and drug enforcement officers insist on a faster procedure to ban NPDs. Introduction of generic legislation, in which clusters of psychotropic drugs are banned in advance, has been mentioned as a possible solution. Here we discuss the pros and cons of such an approach. First, generic legislation could unintentionally increase the expenditures of enforcement, black market practices, administrative burden and health risks for users. Second, it may have a negative impact on research and the development of new treatments. Third, due to the complexity of generic legislation, problems in the enforcement are anticipated due to lack of knowledge about the chemical nomenclature. Finally, various legal options are already available to ban the use, sale and trade of NPDs. We therefore conclude that the currently used scientific benefit-risk evaluation should be continued to limit the adverse health effects of NPDs. Only in emergency cases, where fatal incidents (may) occur, should this approach be overruled.

Elm Tree (Ulmus parvifolia) Bark Bioprocessed with Mycelia of Shiitake (Lentinus edodes) Mushrooms in Liquid Culture: Composition and Mechanism of Protection against Allergic Asthma in Mice.

Science.gov (United States)

Kim, Sung Phil; Lee, Sang Jong; Nam, Seok Hyun; Friedman, Mendel

2016-02-03

Mushrooms can break down complex plant materials into smaller, more digestible and bioactive compounds. The present study investigated the antiasthma effect of an Ulmus parvifolia bark extract bioprocessed in Lentinus edodes liquid mycelium culture (BPUBE) against allergic asthma in chicken egg ovalbumin (OVA)-sensitized/challenged mice. BPUBE suppressed total IgE release from U266B1 cells in a dose-dependent manner without cytotoxicity. Inhibitory activity of BPUBE against OVA-specific IgE secretion in bronchoalveolar lavage fluid (BALF) was observed in OVA-sensitized/challenged asthmatic mice. BPUBE also inhibited OVA-specific IgG and IgG1 secretion into serum from the allergic mice, suggesting the restoration of a Th2-biased immune reaction to a Th1/Th2-balanced status, as indicated by the Th1/Th2 as well as regulatory T cell (Treg) cytokine profile changes caused by BPUBE in serum or BALF. Inflammatory cell counts in BALF and lung histology showed that leukocytosis and eosinophilia induced by OVA-sensitization/challenge were inhibited by the oral administration of BPUBE. Amelioration of eosinophil infiltration near the trachea was associated with reduced eotaxin and vascular cell adhesion molecule-1 (VCAM-1) levels. Changes in proinflammatory mediator levels in BALF suggest that BPUBE decreased OVA-sensitization-induced elevation of leukotriene C4 (LTC4) and prostaglandin D2 (PGD2). The finding that asthma-associated biomarker levels of OVA-sensitized/challenged mice were much more inhibited with BPUBE treatment than NPUBE (not-bioprocessed Ulmus parvifolia extract) treatment suggested the production of new bioactive compounds by the mushroom mycelia that may be involved in enhancing the observed antiasthmatic properties. The possible relation of the composition determined by proximate analysis and GC/MS to observed bioactivity is discussed. The results suggest that the elm tree (Ulmus parvifolia) bark bioprocessed with mycelia of shiitake (Lentinus edodes

A Generic Danish Distribution Grid Model for Smart Grid Technology Testing

DEFF Research Database (Denmark)

Cha, Seung-Tae; Wu, Qiuwei; Østergaard, Jacob

2012-01-01

This paper describes the development of a generic Danish distribution grid model for smart grid technology testing based on the Bornholm power system. The frequency dependent network equivalent (FDNE) method has been used in order to accurately preserve the desired properties and characteristics...... as a generic Smart Grid benchmark model for testing purposes....... by comparing the transient response of the original Bornholm power system model and the developed generic model under significant fault conditions. The results clearly show that the equivalent generic distribution grid model retains the dynamic characteristics of the original system, and can be used...

Comparing Generic Drug Markets in Europe and the United States: Prices, Volumes, and Spending.

Science.gov (United States)

Wouters, Olivier J; Kanavos, Panos G; McKEE, Martin

2017-09-01

Policy Points: Our study indicates that there are opportunities for cost savings in generic drug markets in Europe and the United States. Regulators should make it easier for generic drugs to reach the market. Regulators and payers should apply measures to stimulate price competition among generic drugmakers and to increase generic drug use. To meaningfully evaluate policy options, it is important to analyze historical context and understand why similar initiatives failed previously. Rising drug prices are putting pressure on health care budgets. Policymakers are assessing how they can save money through generic drugs. We compared generic drug prices and market shares in 13 European countries, using data from 2013, to assess the amount of variation that exists between countries. To place these results in context, we reviewed evidence from recent studies on the prices and use of generics in Europe and the United States. We also surveyed peer-reviewed studies, gray literature, and books published since 2000 to (1) outline existing generic drug policies in European countries and the United States; (2) identify ways to increase generic drug use and to promote price competition among generic drug companies; and (3) explore barriers to implementing reform of generic drug policies, using a historical example from the United States as a case study. The prices and market shares of generics vary widely across Europe. For example, prices charged by manufacturers in Switzerland are, on average, more than 2.5 times those in Germany and more than 6 times those in the United Kingdom, based on the results of a commonly used price index. The proportion of prescriptions filled with generics ranges from 17% in Switzerland to 83% in the United Kingdom. By comparison, the United States has historically had low generic drug prices and high rates of generic drug use (84% in 2013), but has in recent years experienced sharp price increases for some off-patent products. There are policy

Endogenous versus exogenous generic reference pricing for pharmaceuticals.

Science.gov (United States)

Antoñanzas, F; Juárez-Castelló, C A; Rodríguez-Ibeas, R

2017-12-01

In this paper we carry out a vertical differentiation duopoly model applied to pharmaceutical markets to analyze how endogenous and exogenous generic reference pricing influence competition between generic and branded drugs producers. Unlike the literature, we characterize for the exogenous case the equilibrium prices for all feasible relevant reference prices. Competition is enhanced after the introduction of a reference pricing system. We also compare both reference pricing systems on welfare grounds, assuming two different objective functions for health authorities: (i) standard social welfare and (ii) gross consumer surplus net of total pharmaceutical expenditures. We show that regardless of the objective function, health authorities will never choose endogenous reference pricing. When health authorities are paternalistic, the exogenous reference price that maximizes standard social welfare is such that the price of the generic drug is the reference price while the price of the branded drug is higher than the reference price. When health authorities are not paternalistic, the optimal exogenous reference price is such that the price of the branded drug is the reference price while the price of the generic drug is lower than the reference price.

Development of a generic virus behavioural detector: a preview ...

African Journals Online (AJOL)

The Generic Virus Behavioral Detector (GVBD) is a system (program) that monitors various system activities; reading and writing block of disks and memory and the use of Interrupts. A technique for its realisation is presented. Key Words: Computer virus, interrupts, handlers, GVBD (Generic Virus Behavioral Detector).

Factors influencing the preference for purchasing generic drugs in a Southern Brazilian city

Directory of Open Access Journals (Sweden)

Marília Cruz Guttier

Full Text Available ABSTRACT OBJECTIVE The objective of this study is to identify factors associated with the preference for purchasing generic drugs in a medium-sized municipality in Southern Brazil. METHODS We have analyzed data from a population-based cross-sectional study conducted in 2012 with a sample of 2,856 adults (≥ 20 years old. The preference for purchasing generic drugs was the main outcome. The explanatory variables were the demographic and socioeconomic variables. Statistical analyses included Poisson regressions. RESULTS The preference for purchasing generic drugs was 63.2% (95%CI 61.4–64.9. The variables correlated with this preference in the fully adjusted models were: male (prevalence ratio [PR] = 1.08; 95%CI 1.03–1.14, age of 20–39 years (PR = 1.10; 95%CI 1.02–1.20, low socioeconomic status (PR = 1.15; 95%CI 1.03–1.28, and good knowledge about generic drugs (PR= 4.66; 95%CI 2.89–7.52. Among those who preferred to purchase generic drugs, 55.1% have reported accepting to replace the prescribed drug (if not a generic with the equivalent generic drug. Another correlate of the preference for purchasing generic drugs was because individuals consider their quality equivalent to reference medicines (PR = 2.15; 95%CI 1.93–2.41. CONCLUSIONS Knowledge about generic drugs was the main correlate of the preference for purchasing generic drugs. The greater the knowledge or positive perception about generic drugs, the greater is the preference to purchase them. Therefore, educational campaigns for healthcare professionals and consumers appear to be the best strategy for expanding the use of generic drugs in Brazil.

40 CFR 721.10017 - Amine terminated bisphenol A diglycidyl ether polymer (generic).

Science.gov (United States)

2010-07-01

... diglycidyl ether polymer (generic). 721.10017 Section 721.10017 Protection of Environment ENVIRONMENTAL... ether polymer (generic). (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substances identified generically as amine terminated bisphenol A diglycidyl ether polymer (PMNs P...

GENERIC DRUG IN GLOBAL MARKET AND REGULATORY ENVIRONMENT

OpenAIRE

Pankaj Kumar*, Bharti Mangla2, Satbir Singh, Arapna Rana

2017-01-01

Different regulatory authorities regulate the drug development in various countries of the world. Various Regulatory authority for generic drug application Food and Drug Administration (FDA), European Medicines Agency (EMA), Pharmaceutical and Medical Devices Agency (PMDA), Health Product and Food Branch (HPFB) Central Drug Standard of Organization (CDSO). Generic manufacturers may file an abbreviated New Drug Application (ANDA) that incorporates the safety/effectiveness data submitted by ori...

Building the Commercial Education Professional Competency Profile

Directory of Open Access Journals (Sweden)

Isabel Araya-Muñoz

2012-12-01

Full Text Available This paper provides a complete description of the Commercial Education Professional Competency Profile that resulted from the curricular diagnosis of the Licenciatura en Educación Comercial , at the Universidad Nacional, Costa Rica.  The methodological strategy used relies on the principles of research on education. Upon expert validation, written questionnaires were applied to first-year students, students of the licenciatura, practicing professionals and employers. The objective was to describe a particular education situation. Data was analyzed according to two categories: intentions/principles and scope/development. The findings resulted in the characteristics of the Commercial Education professionals, i.e. characteristics related to the discipline, characteristics related to the administrative management of teaching, specific and general characteristics of education and pedagogy, and characteristics associated to human development. Based on those criteria, on the curricular requirements of the information sources and on the curricular perspectives of the Academic Unit, ideas were put into practice to build the competency profile. The ideas proposed comprise the curricular fundamentals of the educational project on which the profile is set out, which include the subject of the study program, the global competency or training goal, the generic competencies as cross-cutting approaches, as well as the –pedagogical and disciplinary− specific competencies. The specific competencies of the discipline are focused on four competency areas: document production, organizational support, technological resources and information management. (1 Translator’s Note: One-year post-Bachelor study program in Commercial Education.

Generic information can retrieve known biological associations: implications for biomedical knowledge discovery.

Directory of Open Access Journals (Sweden)

Herman H H B M van Haagen

Full Text Available MOTIVATION: Weighted semantic networks built from text-mined literature can be used to retrieve known protein-protein or gene-disease associations, and have been shown to anticipate associations years before they are explicitly stated in the literature. Our text-mining system recognizes over 640,000 biomedical concepts: some are specific (i.e., names of genes or proteins others generic (e.g., 'Homo sapiens'. Generic concepts may play important roles in automated information retrieval, extraction, and inference but may also result in concept overload and confound retrieval and reasoning with low-relevance or even spurious links. Here, we attempted to optimize the retrieval performance for protein-protein interactions (PPI by filtering generic concepts (node filtering or links to generic concepts (edge filtering from a weighted semantic network. First, we defined metrics based on network properties that quantify the specificity of concepts. Then using these metrics, we systematically filtered generic information from the network while monitoring retrieval performance of known protein-protein interactions. We also systematically filtered specific information from the network (inverse filtering, and assessed the retrieval performance of networks composed of generic information alone. RESULTS: Filtering generic or specific information induced a two-phase response in retrieval performance: initially the effects of filtering were minimal but beyond a critical threshold network performance suddenly drops. Contrary to expectations, networks composed exclusively of generic information demonstrated retrieval performance comparable to unfiltered networks that also contain specific concepts. Furthermore, an analysis using individual generic concepts demonstrated that they can effectively support the retrieval of known protein-protein interactions. For instance the concept "binding" is indicative for PPI retrieval and the concept "mutation abnormality" is

Commercializing Government-sponsored Innovations: Twelve Successful Buildings Case Studies

Science.gov (United States)

Brown, M. A.; Berry, L. G.; Goel, R. K.

1989-01-01

This report examines the commercialization and use of R and D results funded by DOE's Office of Buildings and Community Systems (OBCS), an office that is dedicated to improving the energy efficiency of the nation's buildings. Three goals guided the research described in this report: to improve understanding of the factors that hinder or facilitate the transfer of OBCS R and D results, to determine which technology transfer strategies are most effective and under what circumstances each is appropriate, and to document the market penetration and energy savings achieved by successfully-commercialized innovations that have received OBCS support. Twelve successfully-commercialized innovations are discussed here. The methodology employed involved a review of the literature, interviews with innovation program managers and industry personnel, and data collection from secondary sources. Six generic technology transfer strategies are also described. Of these, contracting R and D to industrial partners is found to be the most commonly used strategy in our case studies. The market penetration achieved to date by the innovations studied ranges from less than 1% to 100%. For the three innovations with the highest predicted levels of energy savings (i.e., the flame retention head oil burner, low-E windows, and solid-state ballasts), combined cumulative savings by the year 2000 are likely to approach 2 quads. To date the energy savings for these three innovations have been about 0.2 quads. Our case studies illustrate the important role federal agencies can play in commercializing new technologies.

Potential cost savings from generic medicines – protecting the ...

African Journals Online (AJOL)

the difference between brand and generic medicines listed for that algorithm, and also as the median of differences between generic medicines for the same condition. Results: Three of the algorithms .... Protecting the PMBs, as a key element of the new community-rated medical schemes environment, is therefore vital.

Does the market share of generic medicines influence the price level?: a European analysis.

Science.gov (United States)

Dylst, Pieter; Simoens, Steven

2011-10-01

After the expiry of patents for originator medicines, generic medicines can enter the market, and price competition may occur. This process generates savings to the healthcare payer and to patients, but knowledge about the factors affecting price competition in the pharmaceutical market following patent expiry is still limited. This study aimed to investigate the relationship between the market share of generic medicines and the change of the medicine price level in European off-patent markets. Data on medicine volumes and values for 35 active substances were purchased from IMS Health. Ex-manufacturer prices were used, and the analysis was limited to medicines in immediate-release, oral, solid dosage forms. Countries included were Austria, Belgium, Denmark, Germany, France, Italy, the Netherlands, Spain, Sweden and the UK, which constitute a mix of countries with low and high generic medicines market shares. Data were available from June 2002 until March 2007. Market volume has risen in both high and low generic market share countries (+29.27% and +27.40%, respectively), but the cause of the rise is different for the two markets. In low generic market share countries, the rise was caused by the increased use of generic medicines, while in high market share countries, the rise was driven by the increased use of generic medicines and a shift of use from originator to generic medicines. Market value was substantially decreased in high generic market share countries (-26.6%), while the decrease in low generic market share countries was limited (-0.06%). In high generic market share countries, medicine prices dropped by -43.18% versus -21.56% in low market share countries. The extent to which price competition from generic medicines leads to price reductions appears to vary according to the market share of generic medicines. High generic market share countries have seen a larger decrease in medicine prices than low market share countries.

Cisplatin-induced hyponatremia in malignancy: comparison between brand-name and generic formulation.

Science.gov (United States)

Ochi, Nobuaki; Yamane, Hiromichi; Hotta, Katsuyuki; Fujii, Hiromi; Isozaki, Hideko; Honda, Yoshihiro; Yamagishi, Tomoko; Kubo, Toshio; Tanimoto, Mitsune; Kiura, Katsuyuki; Takigawa, Nagio

2014-01-01

Widespread use of generic drugs is considered to be indispensable if reductions in total health care costs are to be achieved, but the market share of such drugs remains low. In general, generic drugs have the same active ingredients as brand-name drugs, but this is not always the case. Thus, toxicity profiles may vary when brand-name and generic drugs are compared. We retrospectively investigated the incidence of hyponatremia in patients receiving brand-name cisplatin (CDDP) and a generic counterpart thereof. We reviewed the medical records of patients treated with brand-name CDDP (n=53) and a generic formulation (n=26), and compared the incidences of hyponatremia and renal toxicity. Toxicities were graded using the Common Terminology Criteria for Adverse Events, version 4.0. Differences between groups were evaluated using the Student's t-test, and the odds ratio for hyponatremia was estimated via logistic regression analysis. Serum creatinine levels after chemotherapy increased significantly in both the brand-name and generic CDDP groups; no significant difference was evident between the two groups. Hyponatremia of grade 3 or above developed in 30.7% of the generic CDDP group compared to 15.1% of the brand-name CDDP group (P=0.011). Multivariate analysis showed that the use of generic CDDP increased the incidence of hyponatremia (odds ratio =5.661, 95% confidence interval =1.403-22.839; P=0.015). Oncologists should be aware that use of a generic CDDP might be associated with more hyponatremia than would use of brand-name CDDP.

Development of the generic drug industry in the US after the Hatch-Waxman Act of 1984

Directory of Open Access Journals (Sweden)

Garth Boehm

2013-09-01

Full Text Available The key events in the development of the US generic drug industry after the Hatch-Waxman Act of 1984 are systematically reviewed, including the process of approval for generic drugs, bioequivalence issues including “switchability”, bioequivalence for complicated dosage forms, patent extension, generic drug safety, generic substitution and low-cost generics. The backlog in generic review, generic drug user fees, and “quality by design” for generic drugs is also discussed. The evolution of the US generic drug industry after the Hatch-Waxman Act in 1984 has afforded several lessons of great benefit to other countries wishing to establish or re-establish a domestic generic drug industry.

Factors influencing anti-asthmatic generic drug consumption in Morocco: 1999-2010.

Science.gov (United States)

Ghanname, Imane; Ahid, Samir; Berrada, Ghizlane; Belaiche, Abdelmjid; Hassar, Mohammed; Cherrah, Yahia

2014-01-01

The increasing availability of generic drugs (GD) resulted in a remarkable reduction in treatment costs that allowed a better access to health care.The aim of this study is to evaluate the share of anti-asthmatic generic drugs during the period 1999-2010 in Morocco and to look at the factors influencing generic development. In this study, we used Moroccan sales data from IMS Health (Intercontinental Marketing Services). The consumption of the drugs was expressed in DDD/1000 inhabitants/day according to the WHO ATC/DDD methodology. Between 1999 and 2010, anti-asthmatic consumption increased from 3.91 to 14.43 DDD/1000 inhabitants/day. The market of anti-asthmatic generic drugs progressed from 1.83 (47%) to 2.18 (23%) DDD/1000 inhabitants/day from 1999 to 2010. In 2010, inhaled glucocorticosteroids ranked first (0.83 DDD/1000 inhabitants/day), followed by inhaled short acting beta agonists (0.73 DDD/1000 inhabitants/day). The number of brands went from 27 in 1999 to 34 in 2010, with a generic share increasing from 55.55% to 70.59%. The number of anti-asthmatic pharmaceutical preparations increased from 57 to 64 during the same period, of which 31 and 42 were generic preparations. In 2010, the total cost of anti-asthmatic dugs was about 22 million euro, the generics representing 14 million euro. Despite the introduction of a compulsory insurance scheme called "AMO", that allows a refund for 69.5% of anti-asthmatic specialties marketed in Morocco, anti-asthmatic generic drug consumption remains limited. The Moroccan market is still largely dominated by the originator drugs with still valid patents.

Generic ICT Skills Profiles: Future Skills for Tomorrow's World.

Science.gov (United States)

International Co-operation Europe Ltd. (ICEL), Brussels, Belgium.

This document describes generic skills profiles relevant to key jobs in information and communications technology (ICT). The profiles cover the main job areas for which the ICT industry is experiencing skills shortages. These types of information are provided for 18 generic job profiles: job description (vision, role, lifestyle); examples of job…

Aging management guideline for commercial nuclear power plants - heat exchangers

International Nuclear Information System (INIS)

Booker, S.; Lehnert, D.; Daavettila, N.; Palop, E.

1994-06-01

This Aging Management Guideline (AMG) describes recommended methods for effective detection and mitigation of age-related degradation mechanisms in commercial nuclear power plant heat exchangers important to license renewal. The intent of this AMG is to assist plant maintenance and operations personnel in maximizing the safe, useful life of these components. It also supports the documentation of effective aging management programs required under the License Renewal Rule 10 CFR 54. This AMG is presented in a manner that allows personnel responsible for performance analysis and maintenance to compare their plant-specific aging mechanisms (expected or already experienced) and aging management program activities to the more generic results and recommendations presented herein

Aging management guideline for commercial nuclear power plants - heat exchangers

Energy Technology Data Exchange (ETDEWEB)

Booker, S.; Lehnert, D.; Daavettila, N.; Palop, E.

1994-06-01

This Aging Management Guideline (AMG) describes recommended methods for effective detection and mitigation of age-related degradation mechanisms in commercial nuclear power plant heat exchangers important to license renewal. The intent of this AMG is to assist plant maintenance and operations personnel in maximizing the safe, useful life of these components. It also supports the documentation of effective aging management programs required under the License Renewal Rule 10 CFR 54. This AMG is presented in a manner that allows personnel responsible for performance analysis and maintenance to compare their plant-specific aging mechanisms (expected or already experienced) and aging management program activities to the more generic results and recommendations presented herein.

Aging management guideline for commercial nuclear power plants-pumps

International Nuclear Information System (INIS)

Booker, S.; Katz, D.; Daavettila, N.; Lehnert, D.

1994-03-01

This Aging Management Guideline (AMG) describes recommended methods for effective detection and mitigation of age-related degradation mechanisms in BWR and PWR commercial nuclear power plant pumps important to license renewal. The intent of this AMG is to assist plant maintenance and operations personnel in maximizing the safe, useful life of these components. It also supports the documentation of effective aging management programs required under the License Renewal Rule 10 CFR Part 54. This AMG is presented in a manner that allows personnel responsible for performance analysis and maintenance to compare their plant-specific aging mechanisms (expected or already experienced) and aging management program activities to the more generic results and recommendations presented herein

Aging management guideline for commercial nuclear power plants-pumps

Energy Technology Data Exchange (ETDEWEB)

Booker, S.; Katz, D.; Daavettila, N.; Lehnert, D. [MDC-Ogden Environmental and Energy Services, Southfield, MI (United States)

1994-03-01

This Aging Management Guideline (AMG) describes recommended methods for effective detection and mitigation of age-related degradation mechanisms in BWR and PWR commercial nuclear power plant pumps important to license renewal. The intent of this AMG is to assist plant maintenance and operations personnel in maximizing the safe, useful life of these components. It also supports the documentation of effective aging management programs required under the License Renewal Rule 10 CFR Part 54. This AMG is presented in a manner that allows personnel responsible for performance analysis and maintenance to compare their plant-specific aging mechanisms (expected or already experienced) and aging management program activities to the more generic results and recommendations presented herein.

U.S. NRC's generic issues program

International Nuclear Information System (INIS)

Kauffman, J.V.; Foster, J.W.

2008-01-01

The United States Nuclear Regulatory Commission (NRC) has a Generic Issues Program (GIP) to address Generic Issues (GI). A GI is defined as 'a regulatory matter involving the design, construction, operation, or decommissioning of several, or a class of, NRC licensees or certificate holders that is not sufficiently addressed by existing rules, guidance, or programs'. This rather legalistic definition has several practical corollaries: First, a GI must involve safety. Second, the issue must involve at least two plants, or it would be a plant-specific issue rather than a GI. Third, the potential safety question must not be covered by existing regulations and guidance (compliance). Thus, the effect of a GI is to potentially change the body of regulations and associated guidance (e.g., regulatory guides). The GIP was started in 1976, thus it is a relatively mature program. Approximately 850 issues have been processed by the program to date. More importantly, even after 30 years, new GIs continue to be proposed. The entire set of Generic Issues (GIs) is updated annually in NUREG-0933, 'A Prioritization of Generic Safety Issues'. GIs normally involve complex questions of safety and regulation. Efficient and effective means of addressing these issues are very important for regulatory effectiveness. If an issue proves to pose a genuine, significant safety question, then swift, effective, enforceable, and cost-effective action needs to be taken. Conversely, if an issue is of little safety significance, the issue should be dismissed in an expeditious manner, avoiding unnecessary expenditure of resources and regulatory burden or uncertainty. This paper provides a summary of the 5-stage program, from identification through the regulatory assessment stage. The paper also includes a discussion of the program's seven criteria, sources of proposed GIs, recent improvements, publicly available information, historical performance, and status of current GIs. (authors)

Consumers' views on generic medicines: a review of the literature.

Science.gov (United States)

Hassali, Mohamed A A; Shafie, Asrul A; Jamshed, Shazia; Ibrahim, Mohamed I M; Awaisu, Ahmed

2009-04-01

To review the literature on consumers' knowledge, attitudes and opinions of the use of generic medicines. A narrative review of studies conducted from 1970 to 2008 on consumers perceptions and views towards generic medicines was performed. An extensive literature search was undertaken using indexing services available at the authors' institution library. The following keywords were used for the search: brand, generic, multisource, medications, medicines, drugs, pharmaceuticals and consumers, customers, and patients. Electronic databases searched were Medline, Inside Web, ISI Web of Knowledge, Science Direct, Springer Link, JSTOR, Proquest, Ebsco Host and Google Scholar. These electronic databases were searched for full text papers published in English from 1970 to October 2008. Twenty studies were identified. Eleven were from the USA, four were from Europe, two were from Canada and one each was from Australia, Brazil and Malaysia. In general, consumers showed mixed reactions towards the use of generic medicines. This was evident from the divergence of views observed by country development level, consumers' socioeconomic characteristics, drug product characteristics, pharmaceutical reimbursement system, policy environment, contact with health care professionals, past experience with medications, and knowledge of the seriousness of a medical condition. Patient confidence and knowledge pertaining to generic medicines use have increased over the past four decades, especially in developed countries. Mass educational efforts, financial incentives, and greater communication among patients and health care professionals were seen as major drivers to the uptake of generic medicines among consumers.

IAEA's experience in compiling a generic component reliability data base

International Nuclear Information System (INIS)

Tomic, B.; Lederman, L.

1988-01-01

Reliability data are an essential part of probabilistic safety assessment. The quality of data can determine the quality of the study as a whole. It is obvious that component failure data originated from the plant being analyzed would be most appropriate. However, in few cases complete reliance on plant experience is possible, mainly because of the rather limited operating experience. Nuclear plants, although of different design, often use fairly similar components, so some of the experience could be combined and transferred from one plant to another. In addition information about component failures is available also from experts with knowledge on component design, manufacturing and operation. That bring us to the importance of assessing generic data. (Generic is meant to be everything that is not plant specific regarding the plant being analyzed). The generic data available in the open literature, can be divided in three broad categories. The first one includes data base used in previous analysis. These can be plant specific or updated from generic with plant specific information (latter case deserve special attention). The second one is based on compilation of plants' operating experience usually based on some kind of event reporting system. The third category includes data sources based on expert opinions (single or aggregate) or combination of expert opinions and other nuclear and non-nuclear experience. This paper reflects insights gained in compiling data from generic data sources and highlights advantages and pitfalls of using generic component reliability data in PSAs

[Two cases of pulmonary aspergilosis, which deteriorated with generic itraconazole].

Science.gov (United States)

Saito, Wakana; Shishikura, Yutaka; Nishimaki, Katsushi; Kikuchi, Tadashi; Sasamori, Kan; Kikuchi, Yoshihiro; Miki, Hiroshi

2014-07-01

We experienced two cases of pulmonary aspergillosis, which deteriorated during treatment with generic itraconazole (ITCZ) because of low plasma concentration. One case was chronic pulmonary aspergillosis and the other was allergic bronchopulmonary aspergillosis (ABPA). Treatment of both cases was started with a brand-name-ITCZ, and changed to a generic ITCZ. Deterioration of pulmonary aspergillosis occurred after 8 months and 9 months from change to generic ITCZ respectively. In the first case, the ITCZ-plasma concentration was 46.9 ng/mL and of OH-ITCZ 96.5 ng/mL with generic ITCZ at the dose of 300 mg/day, but increased to 1,559.7 ng/mL and to 2,485.0 ng/mL with the brand-name-ITCZ 300 mg/day, respectively. In the second case, the ITCZ-plasma concentration was 27.2 ng/mL and of OH-ITCZ 20.1 ng/mL with 150 mg/day for generic ITCZ, but reached 857.3 ng/mL and to 1,144.2 ng/ml with the brand-name-ITCZ 300 mg/day, respectively. After treatment failure, the first case was changed to voriconazole, then brand-name-ITCZ 300 mg/day, and the second case to the brand-name-ITCZ 300 mg/day, with successful clinical course. Plasma concentrations of ITCZ can differ significantly depending on the patient or type of ITCZ. The ITCZ-plasma concentration should be controlled after changing from a brand-name-ITCZ to a generic ITCZ.

Effect of generic issues program on improving safety

International Nuclear Information System (INIS)

Fard, M. R.; Kauffman, J. V.

2010-01-01

The U.S. Nuclear Regulatory Commission (NRC) identifies (by its assessment of plant operation) certain issues involving public health and safety, the common defense and security, or the environment that could affect multiple entities under NRC jurisdiction. The Generic Issues Program (GIP) addresses the resolution of these Generic Issues (GIs). The resolution of these issues may involve new or revised rules, new or revised guidance, or revised interpretation of rules or guidance that affect nuclear power plant licensees, nuclear material certificate holders, or holders of other regulatory approvals. U.S. NRC provides information related to the past and ongoing GIP activities to the general public by the use of three main resources, namely NUREG-0933, 'Resolution of Generic Safety Issues, ' Generic Issues Management Control System (GIMCS), and GIP public web page. GIP information resources provide information such as historical information on resolved GIs, current status of the open GIs, policy documents, program procedures, GIP annual and quarterly reports and the process to contact GIP and propose a GI This paper provides an overview of the GIP and several examples of safety improvements resulting from the resolution of GIs. In addition, the paper provides a brief discussion of a few recent GIs to illustrate how the program functions to improve safety. (authors)

Analysis of the Italian generic medicines retail market: recommendations to enhance long-term sustainability.

Science.gov (United States)

Dylst, Pieter; Vulto, Arnold; Simoens, Steven

2015-02-01

Italy is among the European countries with the lowest uptake of generic medicines. This paper provides a perspective on the Italian generic medicines retail market. Fast market entrance of generic medicines in Italy is hindered by several factors: the existence of Complementary Protection Certificates in the past, the large market for copies and multiple cases of patent linkage. Prices of generic medicines in Italy are low compared to other European countries. To contain pharmaceutical expenditure, pharmaceutical companies are currently forced to pay back in case of overspending, which disproportionally penalizes small and fast growing companies, to which most generic companies belong to. Current demand-side policies do not successfully stimulate the use of generic medicines. The current market environment surrounding the Italian generic medicines retail market (i.e., low prices, low volumes) threatens its long-term sustainability. Recommendations to enhance the long-term sustainability of the Italian generic medicines retail market round off this perspective paper.

Do All Ducks Lay Eggs? The Generic Overgeneralization Effect

Science.gov (United States)

Leslie, Sarah-Jane; Khemlani, Sangeet; Glucksberg, Sam

2011-01-01

Generics are statements such as "tigers are striped" and "ducks lay eggs". They express general, though not universal or exceptionless, claims about kinds (Carlson & Pelletier, 1995). For example, the generic "ducks lay eggs" seems true even though many ducks (e.g. the males) do not lay eggs. The universally quantified version of the statement…

Bioprocessing of low-level radioactive and mixed hazard wastes

International Nuclear Information System (INIS)

Stoner, D.L.

1990-01-01

Biologically-based treatment technologies are currently being developed at the Idaho National Engineering Laboratory (INEL) to aid in volume reduction and/or reclassification of low-level radioactive and mixed hazardous wastes prior to processing for disposal. The approaches taken to treat low-level radioactive and mixed wastes will reflect the physical (e.g., liquid, solid, slurry) and chemical (inorganic and/or organic) nature of the waste material being processed. Bioprocessing utilizes the diverse metabolic and biochemical characteristics of microorganisms. The application of bioadsorption and bioflocculation to reduce the volume of low-level radioactive waste are strategies comparable to the use of ion-exchange resins and coagulants that are currently used in waste reduction processes. Mixed hazardous waste would require organic as well as radionuclide treatment processes. Biodegradation of organic wastes or bioemulsification could be used in conjunction with radioisotope bioadsorption methods to treat mixed hazardous radioactive wastes. The degradation of the organic constituents of mixed wastes can be considered an alternative to incineration, while the use of bioemulsification may simply be used as a means to separate inorganic and organics to enable reclassification of wastes. The proposed technology base for the biological treatment of low-level radioactive and mixed hazardous waste has been established. Biodegradation of a variety of organic compounds that are typically found in mixed hazardous wastes has been demonstrated, degradative pathways determined and the nutritional requirements of the microorganisms are understood. Accumulation, adsorption and concentration of heavy and transition metal species and transuranics by microorganisms is widely recognized. Work at the INEL focuses on the application of demonstrated microbial transformations to process development

Analysis of treatment patterns and persistence on branded and generic medications in major depressive disorder using retrospective claims data

Directory of Open Access Journals (Sweden)

Solem CT

2016-10-01

Full Text Available Caitlyn T Solem,1 Ahmed Shelbaya,2,3 Yin Wan,1 Chinmay G Deshpande,1 Jose Alvir,2 Elizabeth Pappadopulos2 1Pharmerit International, Real World Evidence/Data Analytics, Bethesda, MD, 2Pfizer, Inc., Global Health Outcomes, New York, NY, 3Epidemiology Department of Mailman’s School of Public Health, Columbia University Mailman School of Public Health, New York, NY, USA Background: In major depressive disorder (MDD, treatment persistence is critical to optimize symptom remission, functional recovery, and health care costs. Desvenlafaxine tends to have fewer drug interactions and better tolerability than other MDD drugs; however, its use has not been assessed in the real world.Objective: The aim of the present study is to compare medication persistence and concomitant MDD drug use with branded desvenlafaxine (Pristiq® compared with antidepressant drug groups classified as 1 branded selective serotonin reuptake inhibitors (SSRIs; ie, escitalopram [Lexapro™] and selective serotonin–norepinephrine reuptake inhibitors (SNRIs; ie, venlafaxine [Effexor®], duloxetine [Cymbalta®] and 2 generic SSRIs/SNRIs (ie, escitalopram, citalopram, venlafaxine, fluvoxamine, fluoxetine, sertraline, paroxetine, and duloxetine.Patients and methods: MDD patients (ICD-9-CM codes 296.2, 296.3, with ≥2 prescription fills for study drugs and 12-month preindex continuous enrollment from the MarketScan Commercial Claims and Encounters Database (2009–2013, were included. Time-to-treatment discontinuation (prescription gap ≥45 days was assessed using the Kaplan–Meier curve and Cox model. Concomitant MDD drug use was compared.Results: Of the 273,514 patients included, 14,379 patients were initiated with branded desvenlafaxine, 50,937 patients with other branded SSRIs/SNRIs, and 208,198 patients with generic SSRIs/SNRIs. The number of weeks for treatment discontinuation for branded desvenlafaxine were longer (40.7 [95% CI: 39.3, 42.0] compared with other branded

A Generic Safety Assessment Model for a Trench Type LILW Repository

International Nuclear Information System (INIS)

Lee, Youn-Myoung; Choi, Hee-Joo

2015-01-01

This program is ready for a total system performance assessment and is able to deterministically and probabilistically evaluate the nuclide release from a repository and farther transport into the geosphere and biosphere under various normal circumstances, disruptive events, and scenarios that can occur after a failure of waste packages with associated uncertainty. Despite the conceptual design of a trench type LILW repository system, all parameter values associated with the repository system were assumed for the time being, and the generic model developed through this study should be helpful because the evaluation of such releases is very important. A simple and effective model for a safety assessment of a conceptual trench repository system, in which an LILW that arises from a nuclear power plant and other sources, has been developed. The computer program based on this model has also been developed as a GoldSim template using the commercial GoldSim development tool

A Generic Safety Assessment Model for a Trench Type LILW Repository

Energy Technology Data Exchange (ETDEWEB)

Lee, Youn-Myoung; Choi, Hee-Joo [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2015-05-15

This program is ready for a total system performance assessment and is able to deterministically and probabilistically evaluate the nuclide release from a repository and farther transport into the geosphere and biosphere under various normal circumstances, disruptive events, and scenarios that can occur after a failure of waste packages with associated uncertainty. Despite the conceptual design of a trench type LILW repository system, all parameter values associated with the repository system were assumed for the time being, and the generic model developed through this study should be helpful because the evaluation of such releases is very important. A simple and effective model for a safety assessment of a conceptual trench repository system, in which an LILW that arises from a nuclear power plant and other sources, has been developed. The computer program based on this model has also been developed as a GoldSim template using the commercial GoldSim development tool.

Development of a generic data base for failure rate

International Nuclear Information System (INIS)

Mosleh, A.; Apostolakis, G.

1985-01-01

The data analysis task in a probabilistic risk assessment (PRA) involves the assessment of data needs, the collection of information, and, finally, the analysis of the data to generate estimates for various parameters. This paper describes a framework for developing a data base for component failure rates and presents mathematical methods for the analysis of various types of information. The discussion is focused on the development of generic data bases used in PRAs. For plants without an operating history, the generic distributions are used directly to calculate component unavailability. In the case of plants that have operated for some time, the generic distributions can be used as priors in Bayesian analysis and, thus, specialized by plant-specific experience

'Genericism' in Danish welfare professions

DEFF Research Database (Denmark)

Larsen, Verner

and skills in the basic disciplines of the professions also termed as disciplinary and procedural knowledge '. Thus the main research question for this paper is: What consequences do recent reform actions in Danish welfare education concerning generic competence have on developing professional knowledge...

The impact of price-cap regulations on market entry by generic pharmaceutical firms.

Science.gov (United States)

Zhang, Wei; Sun, Huiying; Guh, Daphne; Anis, Aslam H

2017-04-01

In 1998, the province of Ontario, Canada implemented price-cap '70/90' regulations: the first generic must be priced at ≤70% of the associated brand-name price and subsequent generics must be priced at ≤90% of the first generics' price. The price-cap was further lowered to 50% in 2006 and 25% in 2010 for all generic drugs regardless of the first or subsequent generic entrants. This study assessed the impact of such price-cap regulations on market entry by generic firms using the formulary database from 9 provinces (January 2004-March 2013). A logistic regression was estimated to compare the probability of entry during the three policy periods in Ontario ('70/90', '25', versus '50'). Since different price-caps were subsequently introduced in other provinces, Alberta, British Columbia, New Brunswick and Saskatchewan, difference-in-differences was used to compare market entry. In Ontario, compared with the period '50', generic firms were 76% and 63% less likely to enter markets in the periods '25' and '70/90', respectively. The difference-in-differences showed that the entry probability decreased the most in Ontario during the '25' period from the '50' period. Lowering the price-cap level to 25% leads to a significantly lower probability of market entry by generic firms.

Policy objective of generic medicines from the investment perspective: The case of clopidogrel.

Science.gov (United States)

Elek, Péter; Harsányi, András; Zelei, Tamás; Csetneki, Kata; Kaló, Zoltán

2017-05-01

The objective of generic drug policies in most countries is defined from a disinvestment perspective: reduction in expenditures without compromising health outcomes. However, in countries with restricted access of patients to original patented drugs, the objective of generic drug policies can also be defined from an investment perspective: health gain by improved patient access without need for additional health budget. This study examines the investment aspect of generic medicines by analyzing clopidogrel utilization in European countries between 2004 and 2014 using multilevel panel data models. We find that clopidogrel consumption was strongly affected by affordability constraints before the generic entry around 2009, but this effect decayed by 2014. After controlling for other variables, utilization had a substantially larger trend increase in lower-income European countries than in the higher-income ones. Generic entry increased clopidogrel consumption only in lower- and average-income countries but not in the highest-income ones. An earlier generic entry was associated with a larger effect. The case of clopidogrel indicates that the entrance of generics may increase patient access to effective medicines, most notably in lower-income countries, thereby reducing inequalities between European patients. Policymakers should also consider this investment aspect of generic medicines when designing pharmaceutical policies. Copyright © 2017 Elsevier B.V. All rights reserved.

Potential Clinical and Economic Impact of Switching Branded Medications to Generics

Science.gov (United States)

Straka, Robert J.; Keohane, Denis J.; Liu, Larry Z.

2017-01-01

Switching branded to generic medications has become a common cost-containment measure. Although this is an important objective for health care systems worldwide, the impact of this practice on patient outcomes needs to be carefully considered. We reviewed the literature summarizing the potential clinical and economic consequences of switching from branded to generic medications on patient outcomes. A literature search of peer-reviewed articles published 2003–2013 using key words of “generic switching” or “substitution” was conducted using PubMed, OvidSP, and ScienceDirect. Of 30 articles identified and reviewed, most were related to the diseases of the central nervous system, especially epilepsy. Based on our review, potential impacts of switching fell into 3 broad categories: patient attitudes and adherence, clinical and safety outcomes, and cost and resource utilization. Although in many cases generics may represent an appropriate alternative to branded products, this may not always be the case. Specifically, several studies suggested that switching may negatively impact medication adherence, whereas other studies found that generic switching was associated with poorer clinical outcomes and more adverse events. In some instances, switching accomplished cost savings but did so at increased total cost of care because of increased physician visits or hospitalizations. Although in many cases generics may represent an appropriate alternative, mandatory generic switching may lead to unintended consequences, especially in certain therapeutic areas. Although further study is warranted, based on our review, it may be medically justifiable for physicians and patients to retain the right to request the branded product in certain cases. PMID:26099048

Systematic identification of crystallization kinetics within a generic modelling framework

DEFF Research Database (Denmark)

Abdul Samad, Noor Asma Fazli Bin; Meisler, Kresten Troelstrup; Gernaey, Krist

2012-01-01

A systematic development of constitutive models within a generic modelling framework has been developed for use in design, analysis and simulation of crystallization operations. The framework contains a tool for model identification connected with a generic crystallizer modelling tool-box, a tool...

40 CFR 721.10063 - Halo substituted hydroxy nitrophenyl amide (generic).

Science.gov (United States)

2010-07-01

... amide (generic). 721.10063 Section 721.10063 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10063 Halo substituted hydroxy nitrophenyl amide (generic). (a) Chemical... as halo substituted hydroxy nitrophenyl amide (PMN P-04-792) is subject to reporting under this...

The generic drug user fee amendments: an economic perspective

Science.gov (United States)

Berndt, Ernst R; Murphy, Stephen J

2018-01-01

Abstract Since the vast majority of prescription drugs consumed by Americans are off patent (‘generic’), their regulation and supply is of wide interest. We describe events leading up to the US Congress's 2012 passage of the Generic Drug User Fee Amendments (GDUFA I) as part of the Food and Drug Administration Safety and Innovation Act (FDASIA). Under GDUFA I, generic manufacturers agreed to pay approximately $300 million in fees each year of the five-year program. In exchange, the US Food and Drug Administration (FDA) committed to performance goals. We describe GDUFA I’s FDA commitments, provisions, goals, and annual fee structure and compare it to that entailed in the authorization and implementation of GDUFA II on October 1, 2017. We explain how user fees required under GDUFA I erected barriers to entry and created scale and scope economies for incumbent manufacturers. Congress changed user fees under GDUFA II in part to lessen these incentives. In order to initiate and sustain user fees under GDUFA legislation, FDA requires the submission of self-reported data on generic manufacturers including domestic and foreign facilities. These data are public and our examination of them provides an unprecedented window into the recent organization of generic drug manufacturers supplying the US market. Our results suggest that generic drug manufacturing is increasingly concentrated and foreign. We discuss the implications of this observed market structure for GDUFA II’s implementation among other outcomes. PMID:29707218

A randomized, double-blind, cross-over, phase IV trial of oros-methylphenidate (CONCERTA(®)) and generic novo-methylphenidate ER-C (NOVO-generic).

Science.gov (United States)

Fallu, Angelo; Dabouz, Farida; Furtado, Melissa; Anand, Leena; Katzman, Martin A

2016-08-01

Attention-deficit/hyperactivity disorder (ADHD) is a common neurobehavioral disorder with onset during childhood. Multiple aspects of a child's development are hindered, in both home and school settings, with negative impacts on social, emotional, and cognitive functioning. If left untreated, ADHD is commonly associated with poor academic achievement and low occupational status, as well as increased risk of substance abuse and delinquency. The objective of this study was to evaluate adult ADHD subject reported outcomes when switched from a stable dose of CONCERTA(®) to the same dose of generic Novo-methylphenidate ER-C(®). Randomized, double-blind, cross-over, phase IV trial consisted of two phases in which participants with a primary diagnosis of ADHD were randomized in a 1:1 ratio to 3 weeks of treatment with CONCERTA or generic Novo-Methylphenidate ER-C. Following 3 weeks of treatment, participants were crossed-over to receive the other treatment for an additional 3 weeks. Primary efficacy was assessed through the use of the Treatment Satisfaction Questionnaire for Medication, Version II (TSQM-II). Participants with ADHD treated with CONCERTA were more satisfied in terms of efficacy and side effects compared to those receiving an equivalent dose of generic Novo-Methylphenidate ER-C. All participants chose to continue with CONCERTA treatment at the conclusion of the study. Although CONCERTA and generic Novo-Methylphenidate ER-C have been deemed bioequivalent, however the present findings demonstrate clinically and statistically significant differences between generic and branded CONCERTA. Further investigation of these differences is warranted.

A two-stage bioprocess for hydrogen and methane production from rice straw bioethanol residues.

Science.gov (United States)

Cheng, Hai-Hsuan; Whang, Liang-Ming; Wu, Chao-Wei; Chung, Man-Chien

2012-06-01

This study evaluates a two-stage bioprocess for recovering hydrogen and methane while treating organic residues of fermentative bioethanol from rice straw. The obtained results indicate that controlling a proper volumetric loading rate, substrate-to-biomass ratio, or F/M ratio is important to maximizing biohydrogen production from rice straw bioethanol residues. Clostridium tyrobutyricum, the identified major hydrogen-producing bacteria enriched in the hydrogen bioreactor, is likely utilizing lactate and acetate for biohydrogen production. The occurrence of acetogenesis during biohydrogen fermentation may reduce the B/A ratio and lead to a lower hydrogen production. Organic residues remained in the effluent of hydrogen bioreactor can be effectively converted to methane with a rate of 2.8 mmol CH(4)/gVSS/h at VLR of 4.6 kg COD/m(3)/d. Finally, approximately 75% of COD in rice straw bioethanol residues can be removed and among that 1.3% and 66.1% of COD can be recovered in the forms of hydrogen and methane, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

Impact of brand or generic labeling on medication effectiveness and side effects.

Science.gov (United States)

Faasse, Kate; Martin, Leslie R; Grey, Andrew; Gamble, Greg; Petrie, Keith J

2016-02-01

Branding medication with a known pharmaceutical company name or product name bestows on the drug an added assurance of authenticity and effectiveness compared to a generic preparation. This study examined the impact of brand name and generic labeling on medication effectiveness and side effects. 87 undergraduate students with frequent headaches took part in the study. Using a within-subjects counterbalanced design, each participant took tablets labeled either as brand name "Nurofen" or "Generic Ibuprofen" to treat each of 4 headaches. In reality, half of the tablets were placebos, and half were active ibuprofen (400 mg). Participants recorded their headache pain on a verbal descriptor and visual analogue scale prior to taking the tablets, and again 1 hour afterward. Medication side effects were also reported. Pain reduction following the use of brand name labeled tablets was similar in active ibuprofen or a placebo. However, if the tablets had a generic label, placebo tablets were significantly less effective compared to active ibuprofen. Fewer side effects were attributed to placebo tablets with brand name labeling compared to the same placebo tablets with a generic label. Branding of a tablet appears to have conferred a treatment benefit in the absence of an active ingredient, while generic labeled tablets were substantially less effective if they contained no active ingredient. Branding is also associated with reduced attribution of side effects to placebo tablets. Future interventions to improve perceptions of generics may have utility in improving treatment outcomes from generic drugs. (c) 2016 APA, all rights reserved).

76 FR 24920 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

Science.gov (United States)

2011-05-03

... precision requirements or power calculations that justify the proposed sample size, the expected response... Collection; Comment Request; Generic Clearance for the Collection of Qualitative Feedback on Agency Service... Information Collection Request (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback...

76 FR 35069 - Agency Information Collection Activities; Proposed Collection; Comment Request; Generic Clearance...

Science.gov (United States)

2011-06-15

... precision requirements or power calculations that justify the proposed sample size, the expected response...; Proposed Collection; Comment Request; Generic Clearance for the Collection of Qualitative Feedback on... (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery...

78 FR 74175 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

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2013-12-10

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77 FR 52708 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

Science.gov (United States)

2012-08-30

... calculations that justify the proposed sample size, the expected response rate, methods for assessing potential...: Proposed Collection; Comment Request; Generic Clearance for the Collection of Qualitative Feedback on... Information Collection request (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback...

Generic hyper-diversity in Stachybotriaceae

Czech Academy of Sciences Publication Activity Database

Lombard, L.; Houbraken, J.; Decock, C.; Samson, R.A.; Meijer, M.; Réblová, Martina; Groenewald, J.Z.; Crous, P. W.

2016-01-01

Roč. 36, SI Jun (2016), s. 156-246 ISSN 0031-5850 R&D Projects: GA ČR GAP506/12/0038 Institutional support: RVO:67985939 Keywords : biodegraders * generic concept * human and plant pathogens Subject RIV: EF - Botanics Impact factor: 7.511, year: 2016

Safety and efficacy of generic drugs with respect to brand formulation.

Science.gov (United States)

Gallelli, Luca; Palleria, Caterina; De Vuono, Antonio; Mumoli, Laura; Vasapollo, Piero; Piro, Brunella; Russo, Emilio

2013-12-01

Generic drugs are equivalent to the brand formulation if they have the same active substance, the same pharmaceutical form and the same therapeutic indications and a similar bioequivalence respect to the reference medicinal product. The use of generic drugs is indicated from many countries in order to reduce medication price. However some points, such as bioequivalence and the role of excipients, may be clarified regarding the clinical efficacy and safety during the switch from brand to generic formulations. In conclusion, the use of generic drugs could be related with an increased days of disease (time to relapse) or might lead to a therapeutic failure; on the other hand, a higher drug concentration might expose patients to an increased risk of dose-dependent side-effects.

InP-based generic foundry platform for photonic integrated circuits

NARCIS (Netherlands)

Augustin, L.M.; Lemos Alvares Dos Santos, R.M.; den Haan, E.; Kleijn, S.E.F.; Thijs, P.J.A.; Latkowski, S.; Zhao, D.; Yao, W.; Bolk, J.; Ambrosius, H.P.M.M.; Mingaleev, S.; Richter, A.; Bakker, A.; Korthorst, T.

2017-01-01

The standardization of photonic integration processes for InP has led to versatile and easily accessible generic integration platforms. The generic integration platforms enable the realization of a broad range of applications and lead to a dramatic cost reduction in the development costs of photonic

Generic implications of ATWS events at the Salem Nuclear Power Plant: generic implications. Vol. 1

International Nuclear Information System (INIS)

1983-04-01

This report is the first of two volumes. It documents the work of an interoffice, interdisciplinary NRC Task Force established to determine the generic implications of two anticipated transients without scram (ATWS) at the Salem Nuclear Power Plant, Unit 1 on February 22 and 25, 1983. A second report will document the NRC actions to be taken based on the work of the Task Force. The Task Force was established to address three questions: (1) Is there a need for prompt action for similar equipment in other facilities. (2) Are NRC and its licensees learning the sefety-management lessons, and, (3) How should the priority and content of the ATWS rule be adjusted. A number of short-term actions were taken through Bulletins and an Information Notice. Intermediate-term actions to address the generic issues will be addressed in the separate report and implemented through appropriate regulatory mechanisms

Generic phase transitions and profit singularities in Arnol'd's model

International Nuclear Information System (INIS)

Davydov, Aleksei A; Matos, Helena Mena

2007-01-01

For a smooth one-parameter family of pairs of control systems and profit densities on a circle, the generic transitions between optimal rotations and stationary strategies are studied in the problem of maximization of the time-averaged profit on the infinite horizon. It is shown that there are only two types of such transitions, the corresponding singularities of the average profit as a function of the family parameter are found, and it is proved that these singularities are stable under small perturbations of a generic family. The classification of singularities of the maximum average profit is completed for generic families. Bibliography: 16 titles.

Business engineering. Generic Software Architecture in an Object Oriented View

Directory of Open Access Journals (Sweden)

Mihaela MURESAN

2006-01-01

Full Text Available The generic software architecture offers a solution for the the information system's development and implementation. A generic software/non-software model could be developed by integrating the enterprise blueprint concept (Zachman and the object oriented paradigm (Coad's archetype concept. The standardization of the generic software architecture for various specific software components could be a direction of crucial importance, offering the guarantee of the quality of the model and increasing the efficiency of the design, development and implementation of the software. This approach is also useful for the implementation of the ERP systems designed to fit the user’s particular requirements.

77 FR 17493 - Agency Information Collection Activities: Proposed Collection; Comment Request; DOI Generic...

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2012-03-26

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75 FR 80542 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

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2010-12-22

... calculations that justify the proposed sample size, the expected response rate, methods for assessing potential...; Comment Request; Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery... Collection Request (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback on Agency...

76 FR 12140 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

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2011-03-04

... calculations that justify the proposed sample size, the expected response rate, methods for assessing potential...; Comment Request; Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery... Information Collection Request (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback...

76 FR 19826 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

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2011-04-08

... calculations that justify the proposed sample size, the expected response rate, methods for assessing potential... Request; Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery AGENCY... (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback on Agency Service Delivery...

76 FR 17861 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

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2011-03-31

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76 FR 25693 - Agency Information Collection Activities: Proposed Collection; Comment Request; Generic Clearance...

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2011-05-05

... requirements or power calculations that justify the proposed sample size, the expected response rate, methods... Collection; Comment Request; Generic Clearance for the Collection of Qualitative Feedback on Agency Service... Collection Request (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback on Agency...

FDS simulation of the fuel fireball from a hypothetical commercial airliner crash on a generic nuclear power plant

Energy Technology Data Exchange (ETDEWEB)

Luther, Wolfgang [GRS, Forschungsinstitute, Garching (Germany); Mueller, W. Christoph [GRS, Forschungsinstitute, Garching (Germany)], E-mail: mur@grs.de

2009-10-15

In the aftermath of 9/11 events it became clear that the impact of a fast flying commercial airliner hitting the NPP could no longer be excluded as a potential external hazard threatening the nuclear power plant (NPP) safety. One of the potential consequences of the impact is the occurrence of a fireball, large enough to engulf the entire NPP. The knowledge about fireballs from air crashes is rather poor since it is only based on footage shot by chance. From careful physical and chemical examinations using first principles, it can be concluded that the physics and chemistry of the kerosene fireball are similar to BLEVE fireballs in gas tank accidents which have been studied during the last decades. The knowledge from these analyses can be applied to air crash fireball analysis. In order to obtain an adequate understanding of the potential hazards to a NPP engulfed by a fireball a detailed analysis of the fireball is necessary. It is only by a detailed analysis that the effect of the NPP structures on the evolution of the fireball can be derived. Though the safety-relevant parts of the NPP are strong concrete structures, according to IAEA regulations the hypothesized entry of combustion products into ventilation or air supply systems and the entry of fuel into buildings through normal openings have to be analyzed in detail. This requires local transient values of the safety-relevant fireball parameters. With the NPP being a very large structure an adequately detailed simulation requires large computing grids and substantial computing power. With the release of Version 5 of the Fire Dynamic Simulator (FDS) from NIST in 2007 a simulation tool is now available which is capable to perform simulations of large fireballs on sufficiently large computing grids. These fireball simulations can be performed also by any other CFD code in which the relevant models have been implemented. The FDS fireball simulation capabilities were validated with the help of a well

STS-69 postflight presentation

Science.gov (United States)

1995-10-01

A postflight conference of the STS-69 mission is presented. The flightcrew ('The Dog Team') consisted of Cmdr. David Walker, Pilot Kenneth Cockrell, Payload Cmdr. James Voss, and Mission Specialists James Newman and Michael Gernhardt. The mission's primary objective was the deployment and retrieval of the SPARTAN-201 satellite, which investigated the interaction between the Sun and it's solar wind. Other secondary experiments and shuttle payloads included the Wake Shield Facility (WSF), which grew several layers of semiconductor films, the International Extreme Ultraviolet Hitchhiker (IEH-1), the Capillary Pumped Loop-2/Gas Bridge Assembly (CAPL-2/GBA), several Get Away Specials (GAS) experiments, the Electrolysis Performance Improvement Concept Study (EPICS), the Thermal Energy Storage (TES-2) experiment, the Commercial Generic Bioprocessing Apparatus-7 (CGBA-7), the National Institutes of Health-Cells 4 (NIH-C4) experiment, and the Biological Research in Canister-6 (BRIC-6) experiment. Earth views consisted of Saudi Arabia water wells, uncommon vortices over Oman, the Amazon River, the Bahamas, Somalia, a sunset over the Earth's horizon, and two hurricanes, Luis and Marilyn.

Commercializing government-sponsored innovations: Twelve successful buildings case studies

Energy Technology Data Exchange (ETDEWEB)

Brown, M.A.; Berry, L.G.; Goel, R.K.

1989-01-01

This report examines the commercialization and use of R and D results funded by DOE's Office of Buildings and Community Systems (OBCS), an office that is dedicated to improving the energy efficiency of the nation's buildings. Three goals guided the research described in this report: to improve understanding of the factors that hinder or facilitate the transfer of OBCS R and D results, to determine which technology transfer strategies are most effective and under what circumstances each is appropriate, and to document the market penetration and energy savings achieved by successfully-commercialized innovations that have received OBCS support. Twelve successfully-commercialized innovations are discussed here. The methodology employed involved a review of the literature, interviews with innovation program managers and industry personnel, and data collection from secondary sources. Six generic technology transfer strategies are also described. Of these, contracting R and D to industrial partners is found to be the most commonly used strategy in our case studies. The market penetration achieved to date by the innovations studied ranges from less than 1% to 100%. For the three innovations with the highest predicted levels of energy savings (i.e., the flame retention head oil burner, low-E windows, and solid-state ballasts), combined cumulative savings by the year 2000 are likely to approach 2 quads. To date the energy savings for these three innovations have been about 0.2 quads. Our case studies illustrate the important role federal agencies can play in commercializing new technologies. 27 refs., 21 figs., 4 tabs.

76 FR 79198 - Generic Drug User Fee; Public Meeting; Correction

Science.gov (United States)

2011-12-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0381] Generic Drug User Fee; Public Meeting; Correction AGENCY: Food and Drug Administration, HHS. ACTION... meeting entitled ``Generic Drug User Fee.'' The document published with an inadvertent error in the Dates...

Discipline-Specific Compared to Generic Training of Teachers in Higher Education.

Science.gov (United States)

Silva-Fletcher, Ayona; May, Stephen A

A recurrent theme arising in the higher education sector is the suitability and effectiveness of generic versus discipline-specific training of university teachers, who are often recruited based on their disciplinary specialties to become teachers in higher education. We compared two groups of participants who had undergone training using a generic post-graduate certificate in higher education (PGCertGeneric) versus a discipline-specific course in veterinary education (PGCertVetEd). The study was conducted using a survey that allowed comparison of participants who completed PGCertGeneric (n=21) with PGCertVetEd (n=22). Results indicated that participants from both PGCertGeneric and PGCertVetEd considered teaching to be satisfying and important to their careers, valued the teaching observation component of the course, and identified similar training needs. However, the participants of the PGCertVetEd felt that the course made them better teachers, valued the relevance of the components taught, understood course design better, were encouraged to do further courses/reading in teaching and learning, changed their teaching as a result of the course, and were less stressed about teaching as compared to the PGCertGeneric participants (p<.05). It is likely that the PGCertVetEd, which was designed and developed by veterinarians with a wider understanding of the veterinary sector, helped the participants perceive the training course as suited to their needs.

Topological Hausdorff dimension and level sets of generic continuous functions on fractals

International Nuclear Information System (INIS)

Balka, Richárd; Buczolich, Zoltán; Elekes, Márton

2012-01-01

Highlights: ► We examine a new fractal dimension, the so called topological Hausdorff dimension. ► The generic continuous function has a level set of maximal Hausdorff dimension. ► This maximal dimension is the topological Hausdorff dimension minus one. ► Homogeneity implies that “most” level sets are of this dimension. ► We calculate the various dimensions of the graph of the generic function. - Abstract: In an earlier paper we introduced a new concept of dimension for metric spaces, the so called topological Hausdorff dimension. For a compact metric space K let dim H K and dim tH K denote its Hausdorff and topological Hausdorff dimension, respectively. We proved that this new dimension describes the Hausdorff dimension of the level sets of the generic continuous function on K, namely sup{ dim H f -1 (y):y∈R} =dim tH K-1 for the generic f ∈ C(K), provided that K is not totally disconnected, otherwise every non-empty level set is a singleton. We also proved that if K is not totally disconnected and sufficiently homogeneous then dim H f −1 (y) = dim tH K − 1 for the generic f ∈ C(K) and the generic y ∈ f(K). The most important goal of this paper is to make these theorems more precise. As for the first result, we prove that the supremum is actually attained on the left hand side of the first equation above, and also show that there may only be a unique level set of maximal Hausdorff dimension. As for the second result, we characterize those compact metric spaces for which for the generic f ∈ C(K) and the generic y ∈ f(K) we have dim H f −1 (y) = dim tH K − 1. We also generalize a result of B. Kirchheim by showing that if K is self-similar then for the generic f ∈ C(K) for every y∈intf(K) we have dim H f −1 (y) = dim tH K − 1. Finally, we prove that the graph of the generic f ∈ C(K) has the same Hausdorff and topological Hausdorff dimension as K.

The Acquisition of Generic Skills of Culturally-Diverse Student Cohorts

Science.gov (United States)

Keneley, Monica; Jackling, Beverley

2011-01-01

The changing nature of higher education and the structure of graduate labour markets have increased emphasis on employability and graduate outcomes. Universities have responded to this changed environment by embedding generic skills in the curriculum. This paper examines the generic skills that students perceived they acquired in their accounting…

Radiation doses in alternative commercial high-level waste management systems

International Nuclear Information System (INIS)

Schneider, K.J.; Pelto, P.J.; Lavender, J.C.; Daling, P.M.; Fecht, B.A.

1986-01-01

In the commercial high-level waste management system, potential changes are being considered that will augment the benefits of an integral monitored retrievable storage (MRS) facility. The US Department of Energy (DOE) has recognized that alternative options could be implemented in the authorized waste management system (i.e., without an integral MRS facility) to potentially achieve some of the same beneficial effects of the integral MRS system. This paper summarizes those DOE-sponsored analyses related to radiation doses resulting from changes in the waste management system. This report presents generic analyses of aggregated radiation dose impacts to the public and occupational workers, of nine postulated changes in the operation of a spent-fuel management system without an MRS facility

Aging management guideline for commercial nuclear power plants-stationary batteries

International Nuclear Information System (INIS)

Berg, R.; Shao, J.; Krencicki, G.; Giachetti, R.

1994-03-01

The Aging Management Guideline (AMG) describes recommended methods for effective detection and mitigation of age-related degradation mechanisms in BWR and PWR commercial nuclear power plant stationary batteries important to license renewal. The intent of this AMG is to assist plant maintenance and operations personnel in maximizing the safe, useful life of these components. It also supports the documentation of effective aging management programs required under the License Renewal Rule 10 CFR Part 54. This AMG is presented in a manner that allows personnel responsible for performance analysis and maintenance to compare their plant-specific aging mechanisms (expected or already experienced) and aging management program activities to the more generic results and recommendations presented herein

Aging Management Guideline for commercial nuclear power plants: Electrical switchgear

International Nuclear Information System (INIS)

Toman, G.; Gazdzinski, R.; Schuler, K.

1993-07-01

This Aging Management Guideline (AMG) provides recommended methods for effective detection and mitigation of age-related degradation mechanisms in BWR and PWR commercial nuclear power plant electrical switchgear important to license renewal. The latent of this AMG to assist plant maintenance and operations personnel in maximizing the safe, useful life of these components. It also supports the documentation of effective aging management programs required under the License Renewal Rule 10 CFR Part 54. This AMG is presented in a manner which allows personnel responsible for performance analysis and maintenance, to compare their plant-specific aging mechanisms (expected or already experienced) and aging management program activities to the more generic results and recommendations presented herein

Testing properties of generic functions

NARCIS (Netherlands)

Jansson, P.; Jeuring, J.T.; Cabenda, L.; Engels, G.; Kleerekoper, J.; Mak, S.; Overeem, M.; Visser, Kees

2007-01-01

A datatype-generic function is a family of functions indexed by (the structure of) a type. Examples include equality tests, maps and pretty printers. Property based testing tools like QuickCheck and Gast support the de¯nition of properties and test-data generators, and they check if a

How can pharmacist remuneration systems in Europe contribute to generic medicine dispensing?

Directory of Open Access Journals (Sweden)

Dylst P

2012-03-01

Full Text Available Generic medicines can generate larger savings to health care budgets when their use is supported by incentives on both the supply-side and the demand-side. Pharmacists’ remuneration is one factor influencing the dispensing of generic medicines.Objective: The aim of this article is to provide an overview of different pharmacist remuneration systems for generic medicines in Europe, with a view to exploring how pharmacist remuneration systems can contribute to generic medicine dispensing.Methods: Data were obtained from a literature review, a Master thesis in Pharmaceutical Care at the Catholic University of Leuven and a mailing sent to all members of the Pharmaceutical Group of the European Union with a request for information about the local remuneration systems of community pharmacists and the possible existence of reports on discounting practices.Results: Pharmacists remuneration in most European countries consists of the combination of a fixed fee per item and a certain percentage of the acquisition cost or the delivery price of the medicines. This percentage component can be fixed, regressive or capped for very high-cost medicines and acts as a disincentive for dispensing generic medicines. Discounting for generic medicines is common practice in several European countries but information on this practice tends to be confidential. Nevertheless, data for Belgium, France, the Netherlands and United Kingdom indicated that discounting percentages varied from 10% to 70% of the wholesale selling price.Conclusion: Pharmacists can play an important role in the development of a generic medicines market. Pharmacists should not be financially penalized for dispensing generic medicines. Therefore, their remuneration should move towards a fee-for-performance remuneration instead of a price-dependent reimbursement which is currently used in many European countries. Such a fee-for-performance remuneration system provides a stimulus for generic medicines

Medication persistence and the use of generic and brand-name blood pressure-lowering agents.

Science.gov (United States)

Corrao, Giovanni; Soranna, Davide; La Vecchia, Carlo; Catapano, Alberico; Agabiti-Rosei, Enrico; Gensini, Gianfranco; Merlino, Luca; Mancia, Giuseppe

2014-05-01

Because of their lower cost, healthcare systems recommend physicians to prefer generic products, rather than brand-name medicaments. There is then considerable interest and debate concerning safety and effectiveness of generic products. Few studies have compared patients treated with brand-name and generic drugs for adherence to treatment, with somewhat inconsistent results. The primary objective of this study was to compare the risk of discontinuing antihypertensive drug therapy in patients treated with generic or brand-name agents. The 101,618 beneficiaries of the Healthcare system of Lombardy, Italy, aged 18 years or older who were newly treated on monotherapy with antihypertensive generic or brand-name drugs during 2008, were followed until the earliest date among those of the occurrence of treatment discontinuation to whatever antihypertensive drug therapy (outcome), or censoring (death, emigration, 12 months after treatment initiation). Hazard ratios of discontinuation associated with starting on generic or brand-name products (intention-to-treat analysis), and incidence rate ratio of discontinuation during periods on generic and brand-name products (as-treated analysis) were respectively estimated from a cohort and self-controlled case series analyses. Patients who started on generics did not experience a different risk of discontinuation compared with those starting on brand-name agents (hazard ratio: 1.00; 95% confidence interval 0.98-1.02). Discontinuation did not occur with different rates during periods covered by generics or brand-name agents (incidence rate ratio: 1.01; 95% confidence interval 0.96-1.11) within the same individuals. A number of sensitivity and subgroup analyses confirmed the robustness of these findings. Generic products are not responsible for the high rate of discontinuation from antihypertensive drug therapy. Assuming therapeutic equivalence, clinical implication is of prescribing generic drug therapies.

[Acceptance of generic prescribing in general practice: effect of patient education and reference prices].

Science.gov (United States)

Vallès, J A; Barreiro, M; Cereza, G; Ferro, J J; Martínez, M J; Cucurull, E; Barceló, E

2002-01-01

To assess patient acceptance of the substitution of brand-name drugs for generic equivalents in the context of repeat prescriptions for chronic diseases. A prospective multicenter study of drug use was performed. Of the 31 centers included in the study, 8 were randomized to the intervention group and 23 to the control group. For 1 year, patients in the intervention group who visited the center to collect repeat prescriptions received verbal and written information on the advantages and disadvantages of generic and brand name drugs. Data on the number of patients taking brand-name drugs for which generic equivalents were available, as well as the reasons and variables related to refusal of generic drugs (age, gender, education, primary care centre, general practitioner, type of drug and total number of repeat prescriptions) were collected. The percentage of generic drugs among the total number of drugs prescribed was calculated at 2-monthly intervals. A total of 98.9% of the 4620 patients in the intervention group agreed to change to a generic formulation. The percentage of patients accepting generic drugs was significantly associated with the primary care centre, the class of drug, doctors' influence, and patient satisfaction with the drug. Generic prescriptions represented 5.9% in the intervention practices compared with 2.8% in controls. After the intervention, and before the application of reference prices, the percentages were 6.7% and 3.9%, respectively. Immediately after application of the reference prices, the percentages were 8.6% and 6.3%, respectively. Direct patient education is an effective strategy in increasing the prescription of generic equivalents. General practitioners' motivation and knowledge of generic drugs influenced their use. The application of reference prices increased the use of generic equivalents.

Survey of potential health and safety hazards of commercial-scale ethanol production facilities

Energy Technology Data Exchange (ETDEWEB)

Watson, A.P.; Smith, J.G.; Elmore, J.L.

1982-04-01

Generic safety and health aspects of commercial-scale (60 to 600 million L/y) anhydrous ethanol production were identified. Several common feedstocks (grains, roots and fibers, and sugarcane) and fuels (coal, natural gas, wood, and bagasse) were evaluated throughout each step of generic plant operation, from initial milling and sizing through saccharification, fermentation, distillation, and stillage disposal. The fermentation, digestion, or combustion phases are not particularly hazardous, although the strong acids and bases used for hydrolysis and pH adjustment should be handled with the same precautions that every industrial solvent deserves. The most serious safety hazard is that of explosion from grain dust or ethanol fume ignition and boiler/steam line overpressurization. Inhalation of ethanol and carbon dioxide vapors may cause intoxication or asphyxiation in unventilated areas, which could be particularly hazardous near equipment controls and agitating vats. Contact with low-pressure process steam would produce scalding burns. Benzene, used in stripping water from ethanol in the final distillation column, is a suspected leukemogen. Substitution of this fluid by alternative liquids is addressed.

Exploring knowledge perceptions and attitudes about generic medicines among finalyear health science students

Directory of Open Access Journals (Sweden)

Varsha Bangalee

2016-05-01

Full Text Available Background. The use of generic medicines to reduce healthcare costs has become a mandated policy in South Africa. An increase in the use of generics can be achieved through improved knowledge, attitudes and perceptions of generic medicine among healthcare professionals. Objective. To explore knowledge, attitudes and perceptions among final-year health science students on generic medication. Methods. A cross-sectional survey was carried out among the final-year audiology, dental therapy, pharmacy, physiotherapy, occupational therapy, optometry, speech-language and sport science students enrolled at the University of KwaZulu-Natal. A questionnaire was used as the study tool, developed using information adapted from literature reviews. Data analysis was completed using Statistical Package for the Social Sciences (SPSS version 21, and computed using descriptive statistics. Results. Total number of participants was 211, as follows: audiology (n=14, dental therapy (n=15, pharmacy (n=81, physiotherapy (n=41, occupational therapy (n=6, optometry (n=25, speech-language (n=6 and sport science (n=23. A total of 90.0% of students had heard of generic medicines, with 20.9% of them agreeing that generic medicines are less effective than brand-name medicines. Concerning safety, 30.4% believed that brand-name medicines are required to meet higher safety standards than generic medicines. Regarding the need for information on issues pertaining to safety and efficacy of medicines, 53.3% of participants felt that this need was not being met. Conclusion. All groups had knowledge deficits about the safety, quality and efficacy of generic medicines. The dissemination of information about generic medicines may strengthen future knowledge, attitudes and perceptions.

Formulation of Generic Simulation Models for Analyzing Construction Claims

Directory of Open Access Journals (Sweden)

Rifat Rustom

2012-11-01

Full Text Available While there are several techniques for analyzing the impact of claims on time schedule and productivity,very few are considered adequate and comprehensive to consider risks and uncertainties.A generic approach for claims analysis using simulation is proposed. The formulation of the generic methodology presented in this paper depends on three simulation models;As-Planned Model (APM,As-Built Model (ABM, and What-Would-HaveBeenModel(WWHBM. The proposed generic methodology as presented in this paper provides a good basis as a more elaborate approach to better analyze claims and their impacts on project time and productivity utilizing discrete event simulation.The approach proposed allows for scenario analysis to account for the disputed events and workflow disruptions. The proposed models will assist claimants in presenting their cases effectively and professionally.

Generic Crystalline Disposal Reference Case

Energy Technology Data Exchange (ETDEWEB)

Painter, Scott Leroy [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Chu, Shaoping [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Harp, Dylan Robert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Perry, Frank Vinton [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Wang, Yifeng [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2015-02-20

A generic reference case for disposal of spent nuclear fuel and high-level radioactive waste in crystalline rock is outlined. The generic cases are intended to support development of disposal system modeling capability by establishing relevant baseline conditions and parameters. Establishment of a generic reference case requires that the emplacement concept, waste inventory, waste form, waste package, backfill/buffer properties, EBS failure scenarios, host rock properties, and biosphere be specified. The focus in this report is on those elements that are unique to crystalline disposal, especially the geosphere representation. Three emplacement concepts are suggested for further analyses: a waste packages containing 4 PWR assemblies emplaced in boreholes in the floors of tunnels (KBS-3 concept), a 12-assembly waste package emplaced in tunnels, and a 32-assembly dual purpose canister emplaced in tunnels. In addition, three failure scenarios were suggested for future use: a nominal scenario involving corrosion of the waste package in the tunnel emplacement concepts, a manufacturing defect scenario applicable to the KBS-3 concept, and a disruptive glaciation scenario applicable to both emplacement concepts. The computational approaches required to analyze EBS failure and transport processes in a crystalline rock repository are similar to those of argillite/shale, with the most significant difference being that the EBS in a crystalline rock repository will likely experience highly heterogeneous flow rates, which should be represented in the model. The computational approaches required to analyze radionuclide transport in the natural system are very different because of the highly channelized nature of fracture flow. Computational workflows tailored to crystalline rock based on discrete transport pathways extracted from discrete fracture network models are recommended.

Adherence and persistence with branded antidepressants and generic SSRIs among managed care patients with major depressive disorder

Directory of Open Access Journals (Sweden)

Xianchen Liu

2011-03-01

Full Text Available Xianchen Liu1,2, Yi Chen3, Douglas E Faries31Former employee, Eli Lilly and Company, Indianapolis, Indiana, USA; 2Indiana University Department of Psychiatry, Indianapolis, Indiana, USA; 3Eli Lilly and Company, Indianapolis, Indiana, USAObjective: This study compared adherence and persistence of three branded antidepressants: the serotonin and norepinephrine reuptake inhibitors (SNRIs duloxetine and venlafaxine XR, and the selective serotonin reuptake inhibitor (SSRI escitalopram; and generic selective SSRIs, and examined demographic and clinical predictors of adherence and persistence in patients with major depressive disorder in usual care settings.Method: A total of 44,026 patients (18 to 64 years from a large commercial administrative claims database were classified as initiators of duloxetine (n = 7,567, venlafaxine XR (n = 6,106, escitalopram (n = 10,239, or generic SSRIs (n = 20,114 during 2006. Adherence was defined as the medication possession ratio of ≥ 0.8 and persistence as the length of therapy without exceeding a 15-day gap. Pairwise comparisons from multivariate logistic regression and Cox proportional hazards models were performed to examine predictors of adherence and persistence.Results: Adherence rate after one year was significantly higher in duloxetine recipients (38.1% than patients treated with venlafaxine XR (34.0%, escitalopram (25.4%, or generic SSRIs (25.5% (all P < 0.01. Duloxetine recipients stayed on medication longer (158.5 days than those receiving venlafaxine XR (149.6 days, escitalopram (129.1 days, or generic SSRIs (130.2 days (all P < 0.001. Compared with patients treated with escitalopram or generic SSRIs, venlafaxine XR recipients had better adherence and longer persistence (P < 0.001. In addition, being aged 36 years or more, hypersomnia, anxiety disorders, and prior use of antidepressants were associated with increased adherence and persistence, while the opposite was true for comorbid chronic pain

Biodecontamination of concrete

Energy Technology Data Exchange (ETDEWEB)

Rogers, R.D. [Idaho National Engineering Lab., Idaho Falls, ID (United States)

1995-12-31

This paper describes the development and results of a demonstration for a continuous bioprocess for mixed waste treatment. A key element of the process is a unique microbial strain, which tolerates high levels of aromatic solvents and surfactants. This microorganism is the biocatalysis of the continuous flow system designed for processing stored liquid scintillation wastes. During the past year, a process demonstration has been conducted on commercial formulation of liquid scintillation cocktails (LSQ). Based on data obtained from this demonstration, the Ohio Environmental Protection Agency granted the Mound Applied Technologies Laboratory a treatability permit allowing the limited processing of actual mixed waste. Since August 1994, the system has been successfully processing stored {open_quotes}hot{close_quotes} LSC waste. This paper discusses the bioprocess, rates of processing, effluent, and implications of bioprocessing for mixed waste management.

Performance Assessments of Generic Nuclear Waste Repositories in Shale

Science.gov (United States)

Stein, E. R.; Sevougian, S. D.; Mariner, P. E.; Hammond, G. E.; Frederick, J.

2017-12-01

Simulations of deep geologic disposal of nuclear waste in a generic shale formation showcase Geologic Disposal Safety Assessment (GDSA) Framework, a toolkit for repository performance assessment (PA) whose capabilities include domain discretization (Cubit), multiphysics simulations (PFLOTRAN), uncertainty and sensitivity analysis (Dakota), and visualization (Paraview). GDSA Framework is used to conduct PAs of two generic repositories in shale. The first considers the disposal of 22,000 metric tons heavy metal of commercial spent nuclear fuel. The second considers disposal of defense-related spent nuclear fuel and high level waste. Each PA accounts for the thermal load and radionuclide inventory of applicable waste types, components of the engineered barrier system, and components of the natural barrier system including the host rock shale and underlying and overlying stratigraphic units. Model domains are half-symmetry, gridded with Cubit, and contain between 7 and 22 million grid cells. Grid refinement captures the detail of individual waste packages, emplacement drifts, access drifts, and shafts. Simulations are run in a high performance computing environment on as many as 2048 processes. Equations describing coupled heat and fluid flow and reactive transport are solved with PFLOTRAN, an open-source, massively parallel multiphase flow and reactive transport code. Additional simulated processes include waste package degradation, waste form dissolution, radioactive decay and ingrowth, sorption, solubility, advection, dispersion, and diffusion. Simulations are run to 106 y, and radionuclide concentrations are observed within aquifers at a point approximately 5 km downgradient of the repository. Dakota is used to sample likely ranges of input parameters including waste form and waste package degradation rates and properties of engineered and natural materials to quantify uncertainty in predicted concentrations and sensitivity to input parameters. Sandia National

The impact of generic language about ability on children's achievement motivation.

Science.gov (United States)

Cimpian, Andrei

2010-09-01

Nuances in how adults talk about ability may have important consequences for children's sustained involvement and success in an activity. In this study, I tested the hypothesis that children would be less motivated while performing a novel activity if they were told that boys or girls in general are good at this activity (generic language) than if they were told that a particular boy or girl is good at it (non-generic language). Generic language may be detrimental because it expresses normative societal expectations regarding performance. If these expectations are negative, they may cause children to worry about confirming them; if positive, they may cause worries about failing to meet them. Moreover, generic statements may be threatening because they imply that performance is the result of stable traits rather than effort. Ninety-seven 4- to 7-year-olds were asked to play a game in which they succeeded at first but then made a few mistakes. Since young children remain optimistic in achievement situations until the possibility of failure is made clear, I hypothesized that 4- and 5-year-olds would not be affected by the implications of generic language until after they made mistakes; 6- and 7-year-olds, however, may be susceptible earlier. As expected, the older children who heard that boys or girls are good at this game displayed lower motivation (e.g., more negative emotions, lower perceived competence) from the start, while they were still succeeding and receiving praise. Four- and 5-year-olds who heard these generic statements had a similar reaction, but only after they made mistakes. These findings demonstrate that exposure to generic language about ability can be an obstacle to children's motivation and, potentially, their success.

Impact of European pharmaceutical price regulation on generic price competition: a review.

Science.gov (United States)

Puig-Junoy, Jaume

2010-01-01

Although economic theory indicates that it should not be necessary to intervene in the generic drug market through price regulation, most EU countries intervene in this market, both by regulating the maximum sale price of generics (price cap) and by setting the maximum reimbursement rate, especially by means of reference pricing systems. We analyse current knowledge of the impact of direct price-cap regulation of generic drugs and the implementation of systems regulating the reimbursement rate, particularly through reference pricing and similar tools, on dynamic price competition between generic competitors in Europe. A literature search was carried out in the EconLit and PubMed databases, and on Google Scholar. The search included papers published in English or Spanish between January 2000 and July 2009. Inclusion criteria included that studies had to present empirical results of a quantitative nature for EU countries of the impact of price capping and/or regulation of the reimbursement rate (reference pricing or similar systems) on price dynamics, corresponding to pharmacy sales, in the generic drug market. The available evidence indicates that price-cap regulation leads to a levelling off of generic prices at a higher level than would occur in the absence of this regulation. Reference pricing systems cause an obvious and almost compulsory reduction in the consumer price of all pharmaceuticals subject to this system, to a varying degree in different countries and periods, the reduction being greater for originator-branded drugs than for generics. In several countries with a reference pricing system, it was observed that generics with a consumer price lower than the reference price do not undergo price reductions until the reference price is reduced, even when there are other lower-priced generics on the market (absence of price competition below the reference price). Beyond the price reduction forced by the price-cap and/or reference pricing regulation itself

Generic trajectory representation and trajectory following for wheeled robots

DEFF Research Database (Denmark)

Kjærgaard, Morten; Andersen, Nils Axel; Ravn, Ole

2014-01-01

will drive. Safe: Avoid fatal collisions. Based on a survey of existing methods and algorithms the article presents a generic way to represent constraints for different types of robots, a generic way to represent trajectories using Bëzier curves, a method to convert the trajectory so it can be driven...... in a smooth motion, a method to create a safe velocity profile for the robot, and a path following controller....

Generic and Brand Advertising Strategies in a Dynamic Duopoly

OpenAIRE

Frank M. Bass; Anand Krishnamoorthy; Ashutosh Prasad; Suresh P. Sethi

2005-01-01

To increase the sales of their products through advertising, firms must integrate their brand-advertising strategy for capturing market share from competitors and their generic-advertising strategy for increasing primary demand for the category. This paper examines whether, when, and how much brand advertising versus generic advertising should be done. Using differential game theory, optimal advertising decisions are obtained for a dynamic duopoly with symmetric or asymmetric competitors. We ...

Complex dynamics of the generic and brand advertising strategies in duopoly

International Nuclear Information System (INIS)

Qi Jie; Ding Yongsheng; Chen Liang

2008-01-01

By using the optimal profit adjusting strategies, a dynamic advertising competition model in duopoly is extended from Krishnamurthy's static model. Both generic and brand effects for advertising are considered. This model can create complex bifurcating and chaotic behavior for the generic advertising efforts, which lead to chaotic dynamics for the brand advertising and even for the whole system. The asymptotic properties of the symmetric system and the asymmetric system are also investigated, which reflect interactions between the two firms' advertising strategies and relationships between the brand and the generic advertising expenditures

Complex dynamics of the generic and brand advertising strategies in duopoly

Energy Technology Data Exchange (ETDEWEB)

Qi Jie [College of Information Sciences and Technology, Donghua University, Shanghai 200051 (China)], E-mail: jieqi@dhu.edu.cn; Ding Yongsheng [College of Information Sciences and Technology, Donghua University, Shanghai 200051 (China)], E-mail: ysding@dhu.edu.cn; Chen Liang [College of Information Sciences and Technology, Donghua University, Shanghai 200051 (China)

2008-04-15

By using the optimal profit adjusting strategies, a dynamic advertising competition model in duopoly is extended from Krishnamurthy's static model. Both generic and brand effects for advertising are considered. This model can create complex bifurcating and chaotic behavior for the generic advertising efforts, which lead to chaotic dynamics for the brand advertising and even for the whole system. The asymptotic properties of the symmetric system and the asymmetric system are also investigated, which reflect interactions between the two firms' advertising strategies and relationships between the brand and the generic advertising expenditures.

Development of microorganisms for cellulose-biofuel consolidated bioprocessings: metabolic engineers’ tricks

Directory of Open Access Journals (Sweden)

Roberto Mazzoli

2012-10-01

Full Text Available Cellulose waste biomass is the most abundant and attractive substrate for "biorefinery strategies" that are aimed to produce high-value products (e.g. solvents, fuels, building blocks by economically and environmentally sustainable fermentation processes. However, cellulose is highly recalcitrant to biodegradation and its conversion by biotechnological strategies currently requires economically inefficient multistep industrial processes. The need for dedicated cellulase production continues to be a major constraint to cost-effective processing of cellulosic biomass.Research efforts have been aimed at developing recombinant microorganisms with suitable characteristics for single step biomass fermentation (consolidated bioprocessing, CBP. Two paradigms have been applied for such, so far unsuccessful, attempts: a “native cellulolytic strategies”, aimed at conferring high-value product properties to natural cellulolytic microorganisms; b “recombinant cellulolytic strategies”, aimed to confer cellulolytic ability to microorganisms exhibiting high product yields and titers.By starting from the description of natural enzyme systems for plant biomass degradation and natural metabolic pathways for some of the most valuable product (i.e. butanol, ethanol, and hydrogen biosynthesis, this review describes state-of-the-art bottlenecks and solutions for the development of recombinant microbial strains for cellulosic biofuel CBP by metabolic engineering. Complexed cellulases (i.e. cellulosomes benefit from stronger proximity effects and show enhanced synergy on insoluble substrates (i.e. crystalline cellulose with respect to free enzymes. For this reason, special attention was held on strategies involving cellulosome/designer cellulosome-bearing recombinant microorganisms.

A report by the Health and Safety Executive to the Secretary of State for Energy on a review of the generic safety issues of pressurised water reactors

International Nuclear Information System (INIS)

1979-01-01

The Nuclear Installations Inspectorate (NII) has completed a detailed technical study of certain generic safety aspects of the Pressurized Water Reactor (PWR). Although a particular design has been used as a reference, the conclusions reached are not intended to relate to any specific plant. The NII consider that there is no fundamental reason for regarding safety as an obstacle to the selection of a PWR for commercial electricity generation in Britain. Although there are some safety aspects about which present information and investigations are insufficient to allow final conclusions to be reached, and some areas where more work would lead to greater confidence, the NII are satisfied that these issues are not such as to prejudice an immediate decision in principle about the suitability of the PWR for commercial use in Britain. Further progress would appropriately form part of the more detailed review of any specific design of reactor put forward for licensing. Headings of the report include: organization of the review; the PWR; reactor safety issues; basis of judgement; the generic topics (potential plant faults and their analysis, loss of coolant, integrity of primary coolant circuit, fuel elements, reactor protection system, containment, radiological risk in normal operation, radioactive wastes); alternative PWR concepts; risk evaluation; light water reactor safety R and D; conclusions. (author)

40 CFR 721.10097 - Disubstituted benzenesulfonic acid, alkali metal salt (generic).

Science.gov (United States)

2010-07-01

... chemical substance identified generically as disubstituted benzenesulfonic acid, alkali metal salt (PMN P... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Disubstituted benzenesulfonic acid, alkali metal salt (generic). 721.10097 Section 721.10097 Protection of Environment ENVIRONMENTAL...

76 FR 59379 - Proposed Information Collection; Comment Request; Generic Clearance for Research in Development...

Science.gov (United States)

2011-09-26

...-XXXX. Type of Review: Generic Clearance Request. Title: Generic Clearance for Research in Development... information collected through qualitative evaluation methods will inform the disclosure form's design and... Proposed Information Collection; Comment Request; Generic Clearance for Research in Development of...

Interventions promoting the acceptance and uptake of generic medicines: a narrative review of the literature.

Science.gov (United States)

Babar, Z U D; Kan, S W; Scahill, S

2014-09-01

The objective of this paper was to undertake a narrative review of the literature regarding strategies and interventions promoting the acceptance and uptake of generic medicines. A literature search was performed between November 2011 and January 2012 to identify published full text original research articles documenting interventions to promote the use of generic medicines. Keywords used were: "generic medicine", "generic drug", "intervention", "promotion", "acceptance", "uptake", "generic/therapeutic substitution" and their related root words. The electronic databases comprised of Embase (1980 - present), Google, Google Scholar, Medline (1948 - present), PubMed, Science Direct, Scopus, Springer Link and The Cochrane Library. An interpretative narrative synthesis was undertaken and emergent themes analysed and reported. Eighteen studies were included in the final analysis. There were seven main themes which including; education, financial incentives, advertising to promote generic medicines, free generic medicine trials, administrative forms and medicines use review (MUR). These themes were further classified into subthemes. Education was subdivided into consumer and physician education. Financial incentives included the influence of financial incentives on both consumers and physicians. The subthemes in the financial incentives category included the changes in co-payment for consumers, reward payment for physicians and fund-holding schemes. Advertising included the sub-themes of print media and the use of anthropomorphic images, while free generic medicines trial was made up of free vouchers for generic medicines and generic medicines sampling system. The studies have mixed results; some interventions in some settings were useful, while others were not. Not all interventions consistently improved the uptake of generic medicines. There was limited literature available and further work is required to develop a range of interventions to support the uptake of generic

Promoting and regulating generic medicines: Brazil in comparative perspective

Directory of Open Access Journals (Sweden)

Elize Massard da Fonseca

2017-04-01

Full Text Available ABSTRACT Promoting the use of generic drugs can constitute a core instrument for countries’ national pharmaceutical policies, one that reduces drug expenditure while expanding health care access. Despite the potential importance of such policy measures and the differences among national practices, scholars embarking on comparative analysis lack a roadmap for determining which dimensions of generic drug policy to assess and compare. This report fills that gap by considering national rules and regulations across four dimensions deemed crucial to any evaluation: demonstrated therapeutic equivalence; pharmaceutical packaging and labeling; drug prescription; and drug substitution. Furthermore, this report examines how the diverse interests of public and private sector stakeholders might shape generic drug policy and its implementation. To illustrate the challenges and conflicts behind policy development and implementation, this report focuses on the case of Brazil.

A generic interface to reduce the efficiency-stability-cost gap of perovskite solar cells

Science.gov (United States)

Hou, Yi; Du, Xiaoyan; Scheiner, Simon; McMeekin, David P.; Wang, Zhiping; Li, Ning; Killian, Manuela S.; Chen, Haiwei; Richter, Moses; Levchuk, Ievgen; Schrenker, Nadine; Spiecker, Erdmann; Stubhan, Tobias; Luechinger, Norman A.; Hirsch, Andreas; Schmuki, Patrik; Steinrück, Hans-Peter; Fink, Rainer H.; Halik, Marcus; Snaith, Henry J.; Brabec, Christoph J.

2017-12-01

A major bottleneck delaying the further commercialization of thin-film solar cells based on hybrid organohalide lead perovskites is interface loss in state-of-the-art devices. We present a generic interface architecture that combines solution-processed, reliable, and cost-efficient hole-transporting materials without compromising efficiency, stability, or scalability of perovskite solar cells. Tantalum-doped tungsten oxide (Ta-WOx)/conjugated polymer multilayers offer a surprisingly small interface barrier and form quasi-ohmic contacts universally with various scalable conjugated polymers. In a simple device with regular planar architecture and a self-assembled monolayer, Ta-WOx-doped interface-based perovskite solar cells achieve maximum efficiencies of 21.2% and offer more than 1000 hours of light stability. By eliminating additional ionic dopants, these findings open up the entire class of organics as scalable hole-transporting materials for perovskite solar cells.

Generic Structure Potential of Christian Apologetics

Directory of Open Access Journals (Sweden)

Onwu Inya

2012-01-01

Full Text Available Religious texts have been examined by scholars from different theoretical standpoints. However, a close survey of the literature reveals that little attention has been paid to Christian apologetics from a linguistic perspective. Also, an examination of studies along the lines of Generic Structure Potential (henceforth GSP shows that the genre status of Christian apologetics has not been indicated. This gap provides the motivation for this paper, which investigates the GSP of Christian apologetics. Twenty texts written by various key contemporary apologetic writers were purposively selected for the study. The following generic structure potential catalogue was generated:The paper reveals that the elements of the GSP concertedly work to advance, argue for or defend the Christian belief system. The paper also suggests that the model could be applied to other forms of apologetic instances.

Exploring the opinions and experiences of patients with generic substitution: a representative study of Polish society.

Science.gov (United States)

Drozdowska, Aleksandra; Hermanowski, Tomasz

2015-02-01

Generics have the potential to contain drug therapy costs; successful implementation of generic substitution policy largely depends on consumers' willingness to choose generics. This study aims to analyse the opinions, experiences and preferences of Polish patients towards generic medicines. The study was performed in Poland. The survey was conducted in June 2013 by means of face-to-face interviews. Respondents were drawn from the general population according to a population structure. The study covered a representative sample of 1,000 Poles; the results can be generalized to apply to the Polish population at large. Fifty-two percent of respondents declared to be more often choosing generics, twenty-three percent did not have any specific preferences, and twenty-five percent were more willing to choose brand-name medicines. Past experience with cheaper generic medicines, secondary or lower education, low income and residence in specific regions of Poland were all significantly associated with an increased willingness to choose generics. Respondents' attitudes towards generics were mostly influenced by the opinions of doctors and pharmacists. According to respondents, attitudes towards generics among doctors, pharmacists, family and friends, and in the mass media were mostly positive. There was no relationship between the preference of respondents for generics and factors such as their age, life stage, gender, household size or urban/rural locality. As a result of substituting a brand-name drug with its generic equivalent, 72 % of respondents reported that they had not noticed any difference in drug effectiveness; 21 % had experienced a reduced effectiveness of treatment or increased side effects at least once; and 7 % claimed the generic worked better. The majority of respondents who used cheaper substitutes claimed that generics represented good or very good quality. The study demonstrates that, when choosing medicines, Poles rely mainly on the opinions of their

Factors affecting the opinions of family physicians regarding generic drugs – a questionnaire based study

Directory of Open Access Journals (Sweden)

Pawel Lewek

2014-12-01

Full Text Available A range of factors are believed to exert a negative influence on opinions of physicians about generic drugs.The aim of this study was to survey the opinions of primary care doctors on generics, and determine the factors which may affect them. A questionnaire comprising thirty eight questions was distributed among primary care doctors working in seventy out-patient clinics of the Lodzkie province, Poland, during the period of January 1, 2010 – December 31, 2010. A total of170 of 183 participants completed the survey (average age 48.5; 70.0% women: a 92.9%response rate. While 38.8% of physicians claimed that generics were worse than brand name drugs, 54.1% considered them to be better. However, 36.5% of the doctors did not choose generics for their own use. Two key opinions were identified among the responses concerning the effectiveness of generic drugs: use of generic drugs by the physician (p<0.001, and their opinion that pharmacists do inform patients about generic drugs (p<0.05. Although existing evidence confirms that generic and brand name drugs are equally effective, many physicians doubt this, which prevents them from being used as cost effective drug therapy. In order to increase healthcare savings through the use of generics, these factors should be addressed: for example, convincing a physician to adopt generics for personal use may be an efficient way to support more cost effective treatment of his patients.

76 FR 21800 - Agency Information Collection Activities: Submission for OMB Review; Comment Request; Generic...

Science.gov (United States)

2011-04-18

... precision requirements or power calculations that justify the proposed sample size, the expected response... Activities: Submission for OMB Review; Comment Request; Generic Clearance for the Collection of Qualitative... Request (Generic ICR): ``Generic Clearance for the Collection of Qualitative Feedback on Agency Service...

International experiences of promoting generics use and its implications to China.

Science.gov (United States)

Sun, Jing

2013-05-01

To summarize international experiences in promoting use of generics and to extract essence for China's reference. This is a commentary of two systematic reviews about policies to promote use of generics and its implications to China. Price, reimbursement, and generic substitution policies in European countries, and approaches in low and middle income countries in promoting market competition, appropriate intellectual property right protection strategy, and necessary demand side incentives, are all meaningful for China to contain soaring pharmaceutical expenditures, and to maintain the achievements and outcomes of the national health system reform. Effective promotion of generics use must be practice based on the real situation. Tailor-made and comprehensive measures are needed to address both demand and supply sides barriers before achieving tangible cost containment effect without unexpected side effects. © 2013 Wiley Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

Lack of efficacy during the switch from brand to generic allopurinol.

Science.gov (United States)

De Vuono, Antonio; Scicchitano, Francesca; Palleria, Caterina; Russo, Emilio; De Sarro, Giovambattista; Gallelli, Luca

2013-07-01

We report for the first time the lack of therapeutic effects after the switch from a brand formulation of allopurinol to a generic one. A 56-year-old man, with a 5 years history of well-treated gout arthropathy with allopurinol (Zyloric(®) 300 mg/die), developed acute gout arthropathy after the switch from the brand formulation of allopurinol to a generic one. Clinical evaluation and laboratory findings confirmed the diagnosis of acute gout arthropathy. Generic formulation of the drug was dismissed and Zyloric(®) was administered with an improvement of both clinical symptoms and laboratory findings. In conclusion, even if generic formulations are considered to have the same effects in comparison to the brand one, more data are necessaries in order to well define their effectiveness and rationale use. Copyright © 2013 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Perception of antiretroviral generic medicines: one-day survey of HIV-infected patients and their physicians in France.

Directory of Open Access Journals (Sweden)

Christine Jacomet

Full Text Available In the interest of cost effectiveness, switching antiretroviral brand name medications to generics is recommended in France since 2013. The study objective was to evaluate the perception of generics per se and antiretroviral generics in HIV-infected patients and their hospital physicians.556 out of 703 (79% adult HIV+ outpatients and 116 physicians in 33 clinics were included in a multicentric cross-sectional survey performed in September 2013. Patients completed a self-questionnaire on their perception and acceptability of generics. Physicians completed a questionnaire on their acceptability of switching antiretroviral to generic. Socio-demographic data, medical history and HIV history were collected. Among the 556 patients with a median HIV duration of 13 years, 77% were France native, 59% in active employment, 100% covered by social insurance, 95% on antiretroviral therapy. Seventy-six percent of the patients accepted generics and 55% trusted them overall. Antiretroviral generics were accepted by 44% of them but only by 17% if the pill burden was going to increase. The factor significantly associated with acceptability of antiretroviral generics was acceptance of generics per se (p<0.001. Among the 116 physicians following a median of 100 HIV-patients/year, 75% would prescribe generics, dropping to 26% if the combo had to be broken. Factors significantly associated with willingness to prescribe antiretroviral generics were the absence of concern regarding the chemical entity (OR = 0.33, being aware that the patient would accept generics for other pathologies (OR = 2.04 and would accept antiretroviral generics (OR = 1.94. No factor related to sociodemographic conditions, HIV status or comorbidities was associated with the acceptability of antiretroviral generics.Acceptability of antiretroviral generics in this French population was mostly dictated by the patient's and physician's knowledge and use of generics overall. It should be improved

Micro-Electromechanical Affinity Sensor for the Monitoring of Glucose in Bioprocess Media

Directory of Open Access Journals (Sweden)

Lorenz Theuer

2017-06-01

Full Text Available An affinity-viscometry-based micro-sensor probe for continuous glucose monitoring was investigated with respect to its suitability for bioprocesses. The sensor operates with glucose and dextran competing as binding partner for concanavalin A, while the viscosity of the assay scales with glucose concentration. Changes in viscosity are determined with a micro-electromechanical system (MEMS in the measurement cavity of the sensor probe. The study aimed to elucidate the interactions between the assay and a typical phosphate buffered bacterial cultivation medium. It turned out that contact with the medium resulted in a significant long-lasting drift of the assay’s viscosity at zero glucose concentration. Adding glucose to the medium lowers the drift by a factor of eight. The cglc values measured off-line with the glucose sensor for monitoring of a bacterial cultivation were similar to the measurements with an enzymatic assay with a difference of less than ±0.15 g·L−1. We propose that lectin agglomeration, the electro-viscous effect, and constitutional changes of concanavalin A due to exchanges of the incorporated metal ions may account for the observed viscosity increase. The study has demonstrated the potential of the MEMS sensor to determine sensitive viscosity changes within very small sample volumes, which could be of interest for various biotechnological applications.

Quality by control: Towards model predictive control of mammalian cell culture bioprocesses.

Science.gov (United States)

Sommeregger, Wolfgang; Sissolak, Bernhard; Kandra, Kulwant; von Stosch, Moritz; Mayer, Martin; Striedner, Gerald

2017-07-01

The industrial production of complex biopharmaceuticals using recombinant mammalian cell lines is still mainly built on a quality by testing approach, which is represented by fixed process conditions and extensive testing of the end-product. In 2004 the FDA launched the process analytical technology initiative, aiming to guide the industry towards advanced process monitoring and better understanding of how critical process parameters affect the critical quality attributes. Implementation of process analytical technology into the bio-production process enables moving from the quality by testing to a more flexible quality by design approach. The application of advanced sensor systems in combination with mathematical modelling techniques offers enhanced process understanding, allows on-line prediction of critical quality attributes and subsequently real-time product quality control. In this review opportunities and unsolved issues on the road to a successful quality by design and dynamic control implementation are discussed. A major focus is directed on the preconditions for the application of model predictive control for mammalian cell culture bioprocesses. Design of experiments providing information about the process dynamics upon parameter change, dynamic process models, on-line process state predictions and powerful software environments seem to be a prerequisite for quality by control realization. © 2017 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A new generic system for the pantropical Caesalpinia group (Leguminosae

Directory of Open Access Journals (Sweden)

Edeline Gagnon

2016-10-01

Full Text Available The Caesalpinia group is a large pantropical clade of ca. 205 species in subfamily Caesalpinioideae (Leguminosae in which generic delimitation has been in a state of considerable flux. Here we present new phylogenetic analyses based on five plastid and one nuclear ribosomal marker, with dense taxon sampling including 172 (84% of the species and representatives of all previously described genera in the Caesalpinia group. These analyses show that the current classification of the Caesalpinia group into 21 genera needs to be revised. Several genera (Poincianella, Erythrostemon, Cenostigma and Caesalpinia sensu Lewis, 2005 are non-monophyletic and several previously unclassified Asian species segregate into clades that merit recognition at generic rank. In addition, the near-completeness of our taxon sampling identifies three species that do not belong in any of the main clades and these are recognised as new monospecific genera. A new generic classification of the Caesalpinia group is presented including a key for the identification of genera, full generic descriptions, illustrations (drawings and photo plates of all genera, and (for most genera the nomenclatural transfer of species to their correct genus. We recognise 26 genera, with reinstatement of two previously described genera (Biancaea Tod., Denisophytum R. Vig., re-delimitation and expansion of several others (Moullava, Cenostigma, Libidibia and Erythrostemon, contraction of Caesalpinia s.s. and description of four new ones (Gelrebia, Paubrasilia, Hererolandia and Hultholia, and make 75 new nomenclatural combinations in this new generic system.

GenMed 010: a one day workshop on generic medicines

Directory of Open Access Journals (Sweden)

Shankar PR

2011-03-01

Full Text Available This report outlines the content of a one-day workshop onGeneric Medicines that was held at KIST Medical College,Lalitpur, Nepal on 13th December 2010, which was attendedby 32 delegates from different institutions in Nepal, includingpharmacists, pharmacologists and medical doctors. Rightmedicine, right patient, right dose, right frequency andduration, right information and right monitoring areconditions to be fulfilled for the rational use of medicine(RUM. The World Health Organization (WHO defines genericmedicine as ‘a pharmaceutical product, usually intended to beinterchangeable with the innovator product, marketed afterthe expiry of patent or other exclusivity rights’. Economicfactors, supportive legislation and regulation, public andprofessional acceptance and quality assurance are keyenabling factors promoting use of generics. Increased patentprotection for medicines and removing process patents is akey feature of new trade agreements and newer medicines fordiseases like HIV/AIDS, tuberculosis and infectious diseasesare likely to be more expensive. The Medicine andTherapeutics Committee (MTC can play a key role inpromoting generic medicine use in institutions.Nepal being among the Least Developed Countries (LDCsneed not provide patent protection for medicines until 31stDecember 2015. Only a few ‘true’ generics are available inNepal and there is huge cost variation in the price of differentbranded generics. Clinicians have concerns about the qualityof medicines in general, substitution of poor quality brands bypharmacists and about therapeutic substitution. Genericshave to meet the same regulatory requirements and bebioequivalent to reference preparations assuring their quality.

Generic component failure data base

International Nuclear Information System (INIS)

Eide, S.A.; Calley, M.B.

1992-01-01

This report discusses comprehensive component generic failure data base which has been developed for light water reactor probabilistic risk assessments. The Nuclear Computerized Library for Assessing Reactor Reliability (NUCLARR) was used to generate component failure rates. Using this approach, most of the failure rates are based on actual plant data rather then existing estimates

Perception of antiretroviral generic medicines: one-day survey of HIV-infected patients and their physicians in France.

Science.gov (United States)

Jacomet, Christine; Allavena, Clotilde; Peyrol, Fleur; Pereira, Bruno; Joubert, Laurence Morand; Bagheri, Haleh; Cotte, Laurent; Garaffo, Rodolphe; Gerbaud, Laurent; Dellamonica, Pierre

2015-01-01

In the interest of cost effectiveness, switching antiretroviral brand name medications to generics is recommended in France since 2013. The study objective was to evaluate the perception of generics per se and antiretroviral generics in HIV-infected patients and their hospital physicians. 556 out of 703 (79%) adult HIV+ outpatients and 116 physicians in 33 clinics were included in a multicentric cross-sectional survey performed in September 2013. Patients completed a self-questionnaire on their perception and acceptability of generics. Physicians completed a questionnaire on their acceptability of switching antiretroviral to generic. Socio-demographic data, medical history and HIV history were collected. Among the 556 patients with a median HIV duration of 13 years, 77% were France native, 59% in active employment, 100% covered by social insurance, 95% on antiretroviral therapy. Seventy-six percent of the patients accepted generics and 55% trusted them overall. Antiretroviral generics were accepted by 44% of them but only by 17% if the pill burden was going to increase. The factor significantly associated with acceptability of antiretroviral generics was acceptance of generics per se (pantiretroviral generics were the absence of concern regarding the chemical entity (OR = 0.33), being aware that the patient would accept generics for other pathologies (OR = 2.04) and would accept antiretroviral generics (OR = 1.94). No factor related to sociodemographic conditions, HIV status or comorbidities was associated with the acceptability of antiretroviral generics. Acceptability of antiretroviral generics in this French population was mostly dictated by the patient's and physician's knowledge and use of generics overall. It should be improved with an efficient information of both patients and physicians.

Perception of Antiretroviral Generic Medicines: One-Day Survey of HIV-Infected Patients and Their Physicians in France

Science.gov (United States)

Jacomet, Christine; Allavena, Clotilde; Peyrol, Fleur; Pereira, Bruno; Joubert, Laurence Morand; Bagheri, Haleh; Cotte, Laurent; Garaffo, Rodolphe; Gerbaud, Laurent; Dellamonica, Pierre

2015-01-01

Background In the interest of cost effectiveness, switching antiretroviral brand name medications to generics is recommended in France since 2013. The study objective was to evaluate the perception of generics per se and antiretroviral generics in HIV-infected patients and their hospital physicians Methods and Findings 556 out of 703 (79%) adult HIV+ outpatients and 116 physicians in 33 clinics were included in a multicentric cross-sectional survey performed in September 2013. Patients completed a self-questionnaire on their perception and acceptability of generics. Physicians completed a questionnaire on their acceptability of switching antiretroviral to generic. Socio-demographic data, medical history and HIV history were collected. Among the 556 patients with a median HIV duration of 13 years, 77% were France native, 59% in active employment, 100% covered by social insurance, 95% on antiretroviral therapy. Seventy-six percent of the patients accepted generics and 55% trusted them overall. Antiretroviral generics were accepted by 44% of them but only by 17% if the pill burden was going to increase. The factor significantly associated with acceptability of antiretroviral generics was acceptance of generics per se (pantiretroviral generics were the absence of concern regarding the chemical entity (OR = 0.33), being aware that the patient would accept generics for other pathologies (OR = 2.04) and would accept antiretroviral generics (OR = 1.94). No factor related to sociodemographic conditions, HIV status or comorbidities was associated with the acceptability of antiretroviral generics. Conclusions Acceptability of antiretroviral generics in this French population was mostly dictated by the patient’s and physician’s knowledge and use of generics overall. It should be improved with an efficient information of both patients and physicians. PMID:25658627

Origami building blocks: Generic and special four-vertices

Science.gov (United States)

Waitukaitis, Scott; van Hecke, Martin

2016-02-01

Four rigid panels connected by hinges that meet at a point form a four-vertex, the fundamental building block of origami metamaterials. Most materials designed so far are based on the same four-vertex geometry, and little is known regarding how different geometries affect folding behavior. Here we systematically categorize and analyze the geometries and resulting folding motions of Euclidean four-vertices. Comparing the relative sizes of sector angles, we identify three types of generic vertices and two accompanying subtypes. We determine which folds can fully close and the possible mountain-valley assignments. Next, we consider what occurs when sector angles or sums thereof are set equal, which results in 16 special vertex types. One of these, flat-foldable vertices, has been studied extensively, but we show that a wide variety of qualitatively different folding motions exist for the other 15 special and 3 generic types. Our work establishes a straightforward set of rules for understanding the folding motion of both generic and special four-vertices and serves as a roadmap for designing origami metamaterials.

Generic safety documentation model

International Nuclear Information System (INIS)

Mahn, J.A.

1994-04-01

This document is intended to be a resource for preparers of safety documentation for Sandia National Laboratories, New Mexico facilities. It provides standardized discussions of some topics that are generic to most, if not all, Sandia/NM facilities safety documents. The material provides a ''core'' upon which to develop facility-specific safety documentation. The use of the information in this document will reduce the cost of safety document preparation and improve consistency of information

Introduction to Session 5

Science.gov (United States)

Zullo, Luca; Snyder, Seth W.

Production of bio-based products that are cost competitive in the market place requires well-developed operations that include innovative processes and separation solutions. Separations costs can make the difference between an interesting laboratory project and a successful commercial process. Bioprocessing and separations research and development addresses some of the most significant cost barriers in production of bioffuels and bio-based chemicals. Models of integrated biorefineries indicate that success will require production of higher volume fuels in conjunction with high margin chemical products. Addressing the bioprocessing and separations cost barriers will be critical to the overall success of the integrated biorefinery.

Development of generic soil profiles and soil data development for SSI analyses

Energy Technology Data Exchange (ETDEWEB)

Parker, Josh, E-mail: jparker@nuscalepower.com [NuScale Power, 1000 NE Circle Boulevard, Suite 10310, Corvallis, OR 97330 (United States); Khan, Mohsin; Rajagopal, Raj [ARES Corporation, 1990N California Boulevard, Suite 500, Walnut Creek, CA 94596 (United States); Groome, John [NuScale Power, 1000 NE Circle Boulevard, Suite 10310, Corvallis, OR 97330 (United States)

2014-04-01

This paper presents the approach to developing generic soil profiles for the design of reactor building for small modular reactor (SMR) nuclear power plant developed by NuScale Power. The reactor building is a deeply embedded structure. In order to perform soil structure interaction (SSI) analyses, generic soil profiles are required to be defined for the standardized Nuclear Power Plant (NPP) designs for the United States Nuclear Regulatory Commission (NRC) in a design control document (DCD). The development of generic soil profiles is based on utilization of information on generic soil profiles from the new standardized nuclear power plant designs already submitted to the NRC for license certification. Eleven generic soil profiles have been recommended, and those profiles cover a wide range of parameters such as soil depth, shear wave velocity, unit weight, Poisson's ratio, water table, and depth to rock strata. The soil profiles are developed for a range of shear wave velocities between bounds of 1000 fps and 8000 fps as inferred from NRC Standard Review Plan (NUREG 0800) Sections 3.7.1 and 3.7.2. To account for the soil degradation due to seismic events, the strain compatible soil properties are based on the EPRI generic soil degradation curves. In addition, one dimensional soil dynamic response analyses were performed to study the soil layer input motions for performing the SSI analyses.

Biopharmaceutic Risk Assessment of Brand and Generic Lamotrigine Tablets.

Science.gov (United States)

Vaithianathan, Soundarya; Raman, Siddarth; Jiang, Wenlei; Ting, Tricia Y; Kane, Maureen A; Polli, James E

2015-07-06

The therapeutic equivalence of generic and brand name antiepileptic drugs has been questioned by neurologists and the epilepsy community. A potential contributor to such concerns is pharmaceutical quality. The objective was to assess the biopharmaceutic risk of brand name Lamictal 100 mg tablets and generic lamotrigine 100 mg tablets from several manufacturers. Lamotrigine was characterized in terms of the Biopharmaceutics Classification System (BCS), including aqueous solubility and Caco-2 permeability. A panel of pharmaceutical quality tests was also performed on three batches of Lamictal, three batches of Teva generic, and one batch of each of four other generics: appearance, identity, assay, impurity, uniformity of dosage units, disintegration, dissolution, friability, and loss on drying. These market surveillance results indicate that all brand name and generic lamotrigine 100 mg tablets passed all tests and showed acceptable pharmaceutical quality and low biopharmaceutic risk. Lamotrigine was classified as a BCS class IIb drug, exhibiting pH-dependent aqueous solubility and dissolution. At pH 1.2 and 4.5, lamotrigine exhibited high solubility, whereas lamotrigine exhibited low solubility at pH 6.8, including non-sink dissolution. Lamotrigine showed high Caco-2 permeability. The apparent permeability (Papp) of lamotrigine was (73.7 ± 8.7) × 10(-6) cm/s in the apical-to-basolateral (AP-BL) direction and (41.4 ± 1.6) × 10(-6) cm/s in the BL-AP direction, which were higher than metoprolol's AP-BL Papp of (21.2 ± 0.9) × 10(-6) cm/s and BL-AP Papp of (34.6 ± 4.6) × 10(-6) cm/s. Overall, lamotrigine's favorable biopharmaceutics from a drug substance perspective and favorable quality characteristics from a tablet formulation perspective suggest that multisource lamotrigine tablets exhibit a low biopharmaceutic risk.

Generic patch inference

DEFF Research Database (Denmark)

Andersen, Jesper; Lawall, Julia

2010-01-01

A key issue in maintaining Linux device drivers is the need to keep them up to date with respect to evolutions in Linux internal libraries. Currently, there is little tool support for performing and documenting such changes. In this paper we present a tool, spdiff, that identifies common changes...... developers can use it to extract an abstract representation of the set of changes that others have made. Our experiments on recent changes in Linux show that the inferred generic patches are more concise than the corresponding patches found in commits to the Linux source tree while being safe with respect...

Climate Change: Generic Implications for Agriculture

Indian Academy of Sciences (India)

Climate Change: Generic Implications for Agriculture. Increasing carbon dioxide: Good for most crops. Increase in mean temperature: orter ... Increasing rainfall intensity and dry days- more floods and droughts: Higher production variability. Himalayan glaciers to recede: irrigation in IGP gradually becomes less dependable ...

Implementation of IEC Generic Model Type 1 Wind Turbine Generators using RTDS

DEFF Research Database (Denmark)

Cha, Seung-Tae; Wu, Qiuwei; Zhao, Haoran

With the ever increasing penetration of the wind power generation, transmission system operators (TSOs) and distribution system operators (DSOs) are demanding an accurate dynamic wind turbine generator (WTG) models for power system stability studies. However, the confidential requirements from wind...... are useful tools to evaluate the impact of the wind power on the power system stability. Thus, a strong stimulus exists for the development of a generic dynamic model in order to further investigate the dynamic response of WTG under grid disturbances. This paper presents the implementation of the IEC generic...... turbine manufacturers prevent the academia and researchers from working on a real or/and manufacturer specific models. A generic WTG model is of great interest that does not contain the confidential information meanwhile represents the manufacturer specific models. These generic dynamic simulation models...

Knowledge, attitudes and practices of community pharmacists on generic medicines in Palestine: a cross-sectional study.

Science.gov (United States)

Shraim, Naser Y; Al Taha, Tasneem A; Qawasmeh, Rawan F; Jarrar, Hiba N; Shtaya, Maram A N; Shayeb, Lama A; Sweileh, Waleed M

2017-12-28

Generic substitution in several countries has become a common practice. Besides, it is considered as a major cost minimizing strategy meant to contain pharmaceutical expenditure without compromising healthcare quality. However, the safety and quality issues of generic products are of top concerns of general practitioners and health work professionals. This study aimed to investigate community pharmacist's knowledge, attitudes and practices toward generic medicines in Palestine. This study was a cross-sectional observational study employing a self-administered questionnaire. The questionnaire was of four main sections: demographic and practice details of the participants, knowledge, attitudes and the influencing factors related to selection and dispensing of generic medicines. A convenience sampling technique was implemented in this study in which the data collection form was distributed in West Bank- Palestine among a set of practicing pharmacists. Mann-Whitney-U or Kruskal-Wallis tests were used to comparison of different issues as appropriate. P-values of marketing approval of generics, while 87.4% of participants agreed that they should be given the right to substitute generics and the majority (62.3%) support generic substitution for brand name drugs in all cases when a generic is available The main two factors affect pharmacists' selection and dispensing of generic medicines are personal faith in the product (86.1%) and cost effectiveness of generic medicines (84.1%). Generic medicines substitution among pharmacists is widespread and prevalent. Our data found that participant pharmacists in Palestine had basic knowledge with regards to generic medicine. However, their knowledge score pertaining the technical and regulatory aspects of bioequivalence and pharmacokinetic parameters in particular was insufficient.

Patient knowledge, perceptions, and acceptance of generic medicines: a comprehensive review of the current literature

Directory of Open Access Journals (Sweden)

Alrasheedy AA

2014-04-01

Full Text Available Alian A Alrasheedy,1 Mohamed Azmi Hassali,1 Kay Stewart,2 David CM Kong,2 Hisham Aljadhey,3 Mohamed Izham Mohamed Ibrahim,4 Saleh Karamah Al-Tamimi1 1Discipline of Social and Administrative Pharmacy, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia; 2Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia; 3Medication Safety Research Chair, Clinical Pharmacy Department, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 4College of Pharmacy, Qatar University, Doha, Qatar Background: Generic medicines have the same quality, safety, and efficacy as their counterpart original brand medicines. Generic medicines provide the same therapeutic outcomes but at a much cheaper cost, so are promoted in many countries to contain pharmaceutical expenditure and sustain the health care system. Thus, the perspective of patients and medicine consumers as end users of these medicines is an important factor to enhance the use and utilization of generic medicines. The objective of this paper is to review patients’ and consumers’ knowledge, perceptions, acceptance, and views of generic medicines in the current literature. Methods: An extensive literature search was performed in several databases, namely Scopus, PubMed, ISI Web of Knowledge, Proquest, and the Wiley online library, to identify relevant studies published in the English literature for the period 1990–2013. Results: A total of 53 studies were included in the review, comprising 24 studies from Europe, ten from North America, six from Asia, five from Australia and New Zealand, five from the Middle East, one from Africa, one from Latin America, and one from the Caribbean region. A large body of literature has reported misconceptions and negative perceptions about generic medicines on the part of patients and medicine consumers. Moreover, although it is reported in almost all countries, the percentage of consumers who had

A proposal for generic competence assessment in a serious game

Directory of Open Access Journals (Sweden)

María José Bezanilla

2014-01-01

Full Text Available This paper focuses on the design of a serious game for the teaching and assessment of generic competences, placing particular emphasis on the competences assessment aspect. Taking into account important aspects of competence assessment such as context, feedback and transparency, among other aspects, and using the University of Deusto's Generic Competences Assessment Model based on the defining of levels, indicators and descriptors as a reference point, a serious game has been designed for the development and evaluation of two Generic Competences: Problem Solving and Entrepreneurship, aimed at final-year undergraduate and first-year postgraduate students. The design process shows that having a Competence Assessment Model based on levels, indicators and descriptors is of great help in defining the game's scenarios and learning and assessment activities. Serious games can also be excellent resources to help in the development and assessment of generic competences, but not as a unique tool, since the concept of competence in itself is highly complex (integrating knowledge, skills, attitudes and values and some elements might require other methods and techniques for its development. It also reveals the difficulties of evaluating competences in general and through serious games in particular.

40 CFR 721.5452 - Alkali metal salt of halogenated organoborate (generic).

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkali metal salt of halogenated... Specific Chemical Substances § 721.5452 Alkali metal salt of halogenated organoborate (generic). (a... generically as alkali metal salt of halogenated organoborate (PMN P-00-0638) is subject to reporting under...

Generic drugs: myths, facts, and limitations

Directory of Open Access Journals (Sweden)

Antonio Marzo

2012-10-01

Full Text Available Bioequivalence (BE has always been an important pharmaceutical area, particularly (but not solely in Mediterranean region, where the use of generic drugs is a relatively recent development. The lack of new therapeutic molecules has concentrated primary research in the hands of a few large pharmaceutical companies. For smaller companies, this has created opportunities for the development of new formulations of existing drugs (orodispersible tablets that dissolve in the mouth, extended-release tablets, transdermal delivery systems, generic drugs. These applications take advantage of the Abridged New Drug Application (ANDA procedure, which exempts them from a series of expensive investigations and limits the requirement for clinical testing to bioequivalence trials. Since 1991, bioequivalence trials have been regulated by US Food and Drug Administration (FDA and European Medicines Agency (EMA guidelines that provide precise indications on the most specific procedures to be adopted. In spite of these guidelines, however, some aspects of the process have not been fully defined, the most important of which regards the management of endogenous substances. Additional problems are how to manage bioequivalence protocols with drugs that have long half-lives and those whose clearance is characterized by high intrinsic variability. The view that bioequivalence data would be more reliable if they were based on studies in target populations is a myth to be discredited. The present paper reviews issues relative to pharmacokinetics (PK, bioavailability (BA, and bioequivalence, also from an historical viewpoint, and includes a stimulating “questions and answers” section on some key aspects of the bioequivalence of generic drugs.

Molecularly Imprinted Polymer Technology: A Powerful, Generic ...

African Journals Online (AJOL)

Molecularly Imprinted Polymer Technology: A Powerful, Generic, Facile and Cost Effective Alternative for Enantio-recognition and Separation: A Glance at Advances and Applications. ... Tanzania Journal of Science. Journal Home · ABOUT ...

Impacts of Generic Competition and Benefit Management...

Data.gov (United States)

U.S. Department of Health & Human Services — According to findings reported in Impacts of Generic Competition and Benefit Management Practices on Spending for Prescription Drugs - Evidence from Medicares Part D...

Building generic anatomical models using virtual model cutting and iterative registration

Directory of Open Access Journals (Sweden)

Hallgrímsson Benedikt

2010-02-01

Full Text Available Abstract Background Using 3D generic models to statistically analyze trends in biological structure changes is an important tool in morphometrics research. Therefore, 3D generic models built for a range of populations are in high demand. However, due to the complexity of biological structures and the limited views of them that medical images can offer, it is still an exceptionally difficult task to quickly and accurately create 3D generic models (a model is a 3D graphical representation of a biological structure based on medical image stacks (a stack is an ordered collection of 2D images. We show that the creation of a generic model that captures spatial information exploitable in statistical analyses is facilitated by coupling our generalized segmentation method to existing automatic image registration algorithms. Methods The method of creating generic 3D models consists of the following processing steps: (i scanning subjects to obtain image stacks; (ii creating individual 3D models from the stacks; (iii interactively extracting sub-volume by cutting each model to generate the sub-model of interest; (iv creating image stacks that contain only the information pertaining to the sub-models; (v iteratively registering the corresponding new 2D image stacks; (vi averaging the newly created sub-models based on intensity to produce the generic model from all the individual sub-models. Results After several registration procedures are applied to the image stacks, we can create averaged image stacks with sharp boundaries. The averaged 3D model created from those image stacks is very close to the average representation of the population. The image registration time varies depending on the image size and the desired accuracy of the registration. Both volumetric data and surface model for the generic 3D model are created at the final step. Conclusions Our method is very flexible and easy to use such that anyone can use image stacks to create models and

Intermediates and Generic Convergence to Equilibria

DEFF Research Database (Denmark)

Marcondes de Freitas, Michael; Wiuf, Carsten; Feliu, Elisenda

2017-01-01

Known graphical conditions for the generic and global convergence to equilibria of the dynamical system arising from a reaction network are shown to be invariant under the so-called successive removal of intermediates, a systematic procedure to simplify the network, making the graphical conditions...

Licensing of Generic Medicines: Are There Any Challenges Left? A Pharmaceutical Regulatory Perspective.

Science.gov (United States)

Borg, John Joseph; Tomasi, Paolo; Pani, Luca; Aislaitner, George; Pirozynski, Michal; Leufkens, Hubert; Melchiorri, Daniela

2014-01-01

When an innovative product (innovator) is not covered anymore by intellectual property rights, cheaper equivalent medicinal products (generic products) may be marketed and used in clinical practice. The regulation of generic products is well-established, and is primarily based on standard rules for quality, therapeutic equivalence requirements (the latter in most instances proven through a bioequivalence study), and safety data for the innovator. The extensive experience from bringing generic products to the market over the last decades allows the conclusion that they are well-accepted and provide a useful alternative option for cost-effective pharmacotherapy. While supporting this conclusion, there are a number of issues to be considered during the assessment of a generic product application. Six scenarios are described in total, from an efficacy and a safety perspective, where potential concerns with the current regulatory standards could arise in the approval of generic products. We also propose solutions to these scenarios in order to foster debate on these issues.

Is There Evidence to Support Brand to Generic Interchange of the Mycophenolic Acid Products?

Science.gov (United States)

Phillips, Karen; Reddy, Prabashni; Gabardi, Steven

2017-02-01

The uptake of generic immunosuppressants lags comparatively to other drug classes, despite that the Food and Drug Administration (FDA) uses identical bioequivalence standards for all drugs. Transplant societies acknowledge the cost savings associated with generic immunosuppressants and support their use following heart, lung, kidney, or bone marrow transplantation. Seven studies of the pharmacokinetics or clinical efficacy of generic mycophenolate mofetil compared to the innovator product are published; all studies and products were ex-United States. Three studies did not demonstrate any pharmacokinetic differences between generic and innovator products in healthy subjects, achieving FDA bioequivalence requirements. Two studies in renal allograft recipients demonstrated no difference in area under the curves between generic and innovator products, and in one, the maximum concentration (Cmax) fell outside the FDA regulatory range. Two studies revealed no difference in acute organ rejection or graft function in renal allograft recipients. Patient surveys indicate that cost is a barrier to immunosuppressant adherence. Generics present a viable method to reduce costs to payers, patients, and health care systems. Adherence to immunosuppressants is crucial to prevent graft failure. An affordable regimen potentially confers greater adherence. Concerns regarding the presumed inferiority of generic immunosuppressants should be assuaged by regulatory requirements for bioequivalency testing, transplant society position statements, and pharmacokinetic and clinical studies.

HIV/AIDS drugs for Sub-Saharan Africa: how do brand and generic supply compare?

Directory of Open Access Journals (Sweden)

Colleen V Chien

Full Text Available BACKGROUND: Significant quantities of antiretroviral drugs (ARVs to treat HIV/AIDS have been procured for Sub-Saharan Africa for the first time in their 20-year history. This presents a novel opportunity to empirically study the roles of brand and generic suppliers in providing access to ARVs. METHODOLOGY/PRINCIPAL FINDINGS: An observational study of brand and generic supply based on a dataset of 2,162 orders of AIDS drugs for Sub-Saharan Africa reported to the Global Price Reporting Mechanism at the World Health Organization from January 2004-March 2006 was performed. Generic companies supplied 63% of the drugs studied, at prices that were on average about a third of the prices charged by brand companies. 96% of the procurement was of first line drugs, which were provided mostly by generic firms, while the remaining 4%, of second line drugs, was sourced primarily from brand companies. 85% of the generic drugs in the sample were manufactured in India, where the majority of the drugs procured were ineligible for patent protection. The remaining 15% was manufactured in South Africa, mostly under voluntary licenses provided by brand companies to a single generic company. In Sub-Saharan African countries, four first line drugs in the dataset were widely patented, however no general deterrent to generic purchasing based on a patent was detected. CONCLUSIONS/SIGNIFICANCE: Generic and brand companies have played distinct roles in increasing the availability of ARVs in Sub-Saharan Africa. Generic companies provided most of the drugs studied, at prices below those charged by brand companies, and until now, almost exclusively supplied several fixed-dose combination drugs. Brand companies have supplied almost all second line drugs, signed voluntary licenses with generic companies, and are not strictly enforcing patents in certain countries. Further investigation into how price reductions in second line drugs can be achieved and the cheapest drugs can

Comparison of Compounded, Generic, and Innovator-Formulated Itraconazole in Dogs and Cats.

Science.gov (United States)

Renschler, Janelle; Albers, Amanda; Sinclair-Mackling, Hanna; Wheat, Lawrence Joseph

2018-05-14

The triazole antifungal itraconazole may be cost prohibitive in brand name form; therefore, compounded and generic products are often used as alternatives. Itraconazole blood concentrations have not been studied in clinical patients receiving these formulations. Itraconazole bioassay was performed on serum/plasma from 95 dogs and 20 cats receiving itraconazole (compounded from bulk powder, generic pelletized, or brand name) for systemic mycosis treatment. Mean itraconazole concentration was lower in the compounded group (n = 42) as compared with the generic (n = 40) or brand name (n = 33) groups (0.5 µg/mL versus 8.3 µg/mL and 6.5 µg/mL, respectively; P 10 µg/mL; 37.5 and 24%, respectively). Compounded itraconazole should be avoided, but generic itraconazole appears to serve as a reasonable alternative to brand name itraconazole. Therapeutic drug monitoring may be beneficial in all cases.

Generic programming for deterministic neutron transport codes

International Nuclear Information System (INIS)

Plagne, L.; Poncot, A.

2005-01-01

This paper discusses the implementation of neutron transport codes via generic programming techniques. Two different Boltzmann equation approximations have been implemented, namely the Sn and SPn methods. This implementation experiment shows that generic programming allows us to improve maintainability and readability of source codes with no performance penalties compared to classical approaches. In the present implementation, matrices and vectors as well as linear algebra algorithms are treated separately from the rest of source code and gathered in a tool library called 'Generic Linear Algebra Solver System' (GLASS). Such a code architecture, based on a linear algebra library, allows us to separate the three different scientific fields involved in transport codes design: numerical analysis, reactor physics and computer science. Our library handles matrices with optional storage policies and thus applies both to Sn code, where the matrix elements are computed on the fly, and to SPn code where stored matrices are used. Thus, using GLASS allows us to share a large fraction of source code between Sn and SPn implementations. Moreover, the GLASS high level of abstraction allows the writing of numerical algorithms in a form which is very close to their textbook descriptions. Hence the GLASS algorithms collection, disconnected from computer science considerations (e.g. storage policy), is very easy to read, to maintain and to extend. (authors)

Generic Advertising Optimum Budget for Iran’s Milk Industry

Directory of Open Access Journals (Sweden)

H. Shahbazi

2016-05-01

Full Text Available Introduction One of the main targets of planners, decision makers and governments is increasing society health with promotion and production of suitable and healthy food. One of the basic commodities that have important role in satisfaction of required human food is milk. So, some part of government and producer healthy budget allocate to milk consumption promotion by using generic advertising. If effectiveness of advertising budget on profitability is more, producer will have more willing to spend for advertising. Determination of optimal generic advertising budget is one of important problem in managerial decision making in producing firm as well as increase in consumption and profit and decrease in wasting and non-optimality of budget. Materials and Methods: In this study, optimal generic advertising budget intensity index (advertising budget share of production cost was estimated under two different scenarios by using equilibrium replacement model. In equilibrium replacement model, producer surplus are maximized in respect to generic advertising in retail level. According to market where two levels of farm and processing before retail exist and there is trade in farm and retail level, we present different models. Fixed and variable proportion hypothesis is another one. Finally, eight relations are presented for determination of milk generic advertising optimum budget. So, we use data from several resources such as previous studies, national (Iran Static center and international institute (Fao formal data and own estimation. Because there are several estimations in previous studies, we identify some scenarios (in two general scenarios for calculation of milk generic advertising optimum budget. Results and Discussion: Estimation of milk generic advertising optimum budget in scenario 1 shows that in case of one market level, fixed supplies and no trade, optimum budget is 0.4672539 percent. In case of one market level and no trade, optimum

Generic Principles for Resolving Intergroup Conflict.

Science.gov (United States)

Fisher, Ronald J.

1994-01-01

Provides an initial statement of generic principles deemed effective for addressing protracted social conflicts between identity groups. These principles are compatible with certain values for societal organization and approaches to social change, raising questions of value differences between intervenors and the host culture(s). Three case…

Binary mixtures of condensates in generic confining potentials

Energy Technology Data Exchange (ETDEWEB)

Facchi, P [Dipartimento di Matematica and MECENAS, Universita di Bari, I-70125 Bari (Italy); Florio, G; Pascazio, S; Pepe, F V, E-mail: Francesco.Pepe@ba.infn.it [INFN, Sezione di Bari, I-70126 Bari (Italy)

2011-12-16

We study a binary mixture of Bose-Einstein condensates, confined in a generic potential, in the Thomas-Fermi approximation. We search for the zero-temperature ground state of the system, both in the case of fixed numbers of particles and fixed chemical potentials. For generic potentials, we analyze the transition from mixed to separated ground-state configurations as the inter-species interaction increases. We derive a simple formula that enables one to determine the location of the domain walls. Finally, we find criteria for the energetic stability of separated configurations, depending on the number and the position of the domain walls separating the two species. (paper)

Binary mixtures of condensates in generic confining potentials

Science.gov (United States)

Facchi, P.; Florio, G.; Pascazio, S.; Pepe, F. V.

2011-12-01

We study a binary mixture of Bose-Einstein condensates, confined in a generic potential, in the Thomas-Fermi approximation. We search for the zero-temperature ground state of the system, both in the case of fixed numbers of particles and fixed chemical potentials. For generic potentials, we analyze the transition from mixed to separated ground-state configurations as the inter-species interaction increases. We derive a simple formula that enables one to determine the location of the domain walls. Finally, we find criteria for the energetic stability of separated configurations, depending on the number and the position of the domain walls separating the two species.

Binary mixtures of condensates in generic confining potentials

International Nuclear Information System (INIS)

Facchi, P; Florio, G; Pascazio, S; Pepe, F V

2011-01-01

We study a binary mixture of Bose–Einstein condensates, confined in a generic potential, in the Thomas–Fermi approximation. We search for the zero-temperature ground state of the system, both in the case of fixed numbers of particles and fixed chemical potentials. For generic potentials, we analyze the transition from mixed to separated ground-state configurations as the inter-species interaction increases. We derive a simple formula that enables one to determine the location of the domain walls. Finally, we find criteria for the energetic stability of separated configurations, depending on the number and the position of the domain walls separating the two species. (paper)

77 FR 36568 - Proposed Information Collection; Comment Request: Generic Customer Satisfaction Surveys

Science.gov (United States)

2012-06-19

... Collection; Comment Request: Generic Customer Satisfaction Surveys AGENCY: Office of the Chief Information.... This Notice also lists the following information: Title of Proposal: Generic--Customer Satisfaction... to gather this data directly from our customers. HUD will conduct various customer satisfaction...

Might generic OCs create contraceptive price war?

Science.gov (United States)

1987-02-01

Genora 1/35 and 1/50, the 1st generic oral contraceptives (OCs) in the world, are now being marketed in the US. Clinicians interviewed by "Contraceptive Technology Update" (CTU) offer differing opinions as to what this new OC may mean in the marketplace. Products of Rugby Laboratories, the pills are copy products of Ortho Pharmaceutical's ON 1/35 and ON 1/50 formulations. Most clinicians believe that Genora's success or failure in the OC market depends on its eventual retail price. The price difference of $3-$4 may be sufficiently substantial for retailers to charge less for the generic OCs. If that is the case, many doctors may prescribe a pill which will save their patients $4/month. Dr. Mildred Hanson, a Minneapolis gynecologist/obstetrician, feels any cost savings from Genora will have a significant impact on the OC market. She suggests that the less expensive OCs will catch the attention of health maintenance organizations (HMOs) and the business of women who participate in such health plans. Yet James Burns, director of family planning services for the Hartford City Health Department, thinks that even a full-scale retail price war won't have much effect from a clinic standpoint. He reports that clinics are able to obtain contraceptive supplies rather inexpensively through the contracting system. Hanson also expressed doubt over the potential popularity of Genora 1/50 as clinical concerns about the effects of combined OCs on serum lipid levels and carbohydrate metabolism have resulted in a nationwide push toward OCs containing less than 50 micrograms of estrogen. He indicated concern that declines in pharmaceutical house products from pricing competition with generic pills might have a negative impact on contraceptive research and development. Dick Haskitt, director of business planning for Syntex Laboratories, Inc., who will produce the OCs for Rugby, reports that their market research shows that people are very interested in having a generic OC available

Prioritization of generic safety issues

International Nuclear Information System (INIS)

Emrit, R.; Minners, W.; VanderMolen, H.

1983-12-01

This report presents the priority rankings for generic safety issues related to nuclear power plants. The purpose of these rankings is to assist in the timely and efficient allocation of NRC resources for the resolution of those safety issues that have a significant potential for reducing risk. The report focuses on the prioritization of generic safety issues. Issues primarily concerned with the licensing process or environmental protection and not directly related to safety have been excluded from prioritization. The prioritized issues include: TMI Action Plan items under development; previously proposed issues covered by Task Action Plans, except issues designated at Unresolved Safety Issues (USIs) which had already been assigned high priority; and newly-proposed issues. Future supplements to this report will include the prioritization of additional issues. The safety priority rankings are HIGH, MEDIUM, LOW, and DROP and have been assigned on the basis of risk significance estimates, the ratio of risk to costs and other impacts estimated to result if resolutions of the safety issues were implemented, and the consideration of uncertainties and other quantitative or qualitative factors. To the extent practical, estimates are quantitative

Generic communications index: User's manual

International Nuclear Information System (INIS)

Dean, R.S.; Steinbrecher, D.H.; Hennick, A.

1987-12-01

This report is a manual for providing information required to use a special computer program developed by the NRC for indexing generic communications. The program is written in a user-friendly menu driven form using dBASE III programming language. It facilitates use of the required dBASE III search and sort capabilities to access records in a database called Generic Communications Index. This index is made up of one record each for all bulletins, circulars, and information notices, including revisions and supplements, from 1971, when such documentation started, through 1986 (or to the latest update). The program is designed for use by anyone modestly acquainted with the general use of IBM-compatible personal computers. The manual contains both a brief overview and a detailed description of the program, as well as detailed instructions for getting started using the program on a personal computer with either a two-floppy disk or a hard disk system. Included at the end are a brief description of how to handle problems which might occur, and notes on the makeup of the program and database files for help in adding records of communications for future years

Individual Differences in Children's and Parents' Generic Language

Science.gov (United States)

Gelman, Susan A.; Ware, Elizabeth A.; Kleinberg, Felicia; Manczak, Erika M.; Stilwell, Sarah M.

2014-01-01

Generics ("'Dogs' bark") convey important information about categories and facilitate children's learning. Two studies with parents and their 2- or 4-year-old children (N = 104 dyads) examined whether individual differences in generic language use are as follows: (a) stable over time, contexts, and domains, and (b) linked…

How the conceptions of Chinese rhetorical expressions are derived from the corresponding generic sentences

Science.gov (United States)

Zhao, Wenhui

2018-04-01

Generic sentences are simple and intuitive recognition and objective description to the external world in terms of "class". In the long evolutionary process of human being's language, the concepts represented by generic sentences has been internalized to be the defaulted knowledge in people's minds. In Chinese, some rhetorical expressions supported by corresponding generic sentences can be accepted by people. The derivation of these rhetorical expressions from the corresponding generic sentences is an important way for language to evolution, which reflects human's creative cognitive competence. From the perspective of conceptual blend theory and the theory of categorization of the cognitive linguistics, the goal of this paper is to analysis the process of the derivation of the rhetorical expressions from the corresponding generic sentences, which can facilitate the Chinese metaphorical information processing and the corpus construction of Chinese emotion metaphors.

Generic and sequence-variant specific molecular assays for the detection of the highly variable Grapevine leafroll-associated virus 3.

Science.gov (United States)

Chooi, Kar Mun; Cohen, Daniel; Pearson, Michael N

2013-04-01

Grapevine leafroll-associated virus 3 (GLRaV-3) is an economically important virus, which is found in all grapevine growing regions worldwide. Its accurate detection in nursery and field samples is of high importance for certification schemes and disease management programmes. To reduce false negatives that can be caused by sequence variability, a new universal primer pair was designed against a divergent sequence data set, targeting the open reading frame 4 (heat shock protein 70 homologue gene), and optimised for conventional one-step RT-PCR and one-step SYBR Green real-time RT-PCR assays. In addition, primer pairs for the simultaneous detection of specific GLRaV-3 variants from groups 1, 2, 6 (specifically NZ-1) and the outlier NZ2 variant, and the generic detection of variants from groups 1 to 5 were designed and optimised as a conventional one-step multiplex RT-PCR assay using the plant nad5 gene as an internal control (i.e. one-step hexaplex RT-PCR). Results showed that the generic and variant specific assays detected in vitro RNA transcripts from a range of 1×10(1)-1×10(8) copies of amplicon per μl diluted in healthy total RNA from Vitis vinifera cv. Cabernet Sauvignon. Furthermore, the assays were employed effectively to screen 157 germplasm and 159 commercial field samples. Thus results demonstrate that the GLRaV-3 generic and variant-specific assays are prospective tools that will be beneficial for certification schemes and disease management programmes, as well as biological and epidemiological studies of the divergent GLRaV-3 populations. Copyright © 2013 Elsevier B.V. All rights reserved.

40 CFR 721.10153 - Modified methyl methacrylate, 2-hydroxyethyl methacrylate polymer (generic).

Science.gov (United States)

2010-07-01

...-hydroxyethyl methacrylate polymer (generic). 721.10153 Section 721.10153 Protection of Environment...-hydroxyethyl methacrylate polymer (generic). (a) Chemical substance and significant new uses subject to... methacrylate polymer (PMN P-08-6) is subject to reporting under this section for the significant new uses...

Relevance of variation in use of terminology to define generic pharmaceutical products

Directory of Open Access Journals (Sweden)

Elize Massard da Fonseca

2015-02-01

Full Text Available The World Health Organization (WHO promotes the use of generic drug policies to foster competition in the pharmaceutical sector, reduce drug prices, and increase access to therapeutic drugs. However, little is known about how countries implement these policies. This article describes different terminology adopted by national regulatory authorities to define generic versus proprietary drug products in developing countries, including those in Latin America, and challenges that arise in their application of WHO guidelines, such as labeling issues. The author concludes that variation in generics terminology in these countries is a result of institutional context (i.e., the public sector setting as well as the body of laws and regulations that exists in the country and policy legacies, such as intellectual property regimes, and highlights the need for further analysis of pharmaceutical regulations to improve understanding of the barriers and political implications of generic drug policies.

Relevance of variation in use of terminology to define generic pharmaceutical products.

Science.gov (United States)

Fonseca, Elize Massard da

2015-02-01

The World Health Organization (WHO) promotes the use of generic drug policies to foster competition in the pharmaceutical sector, reduce drug prices, and increase access to therapeutic drugs. However, little is known about how countries implement these policies. This article describes different terminology adopted by national regulatory authorities to define generic versus proprietary drug products in developing countries, including those in Latin America, and challenges that arise in their application of WHO guidelines, such as labeling issues. The author concludes that variation in generics terminology in these countries is a result of institutional context (i.e., the public sector setting as well as the body of laws and regulations that exists in the country) and policy legacies, such as intellectual property regimes, and highlights the need for further analysis of pharmaceutical regulations to improve understanding of the barriers and political implications of generic drug policies.

A generic access to shot-based data for European Tokamaks

Energy Technology Data Exchange (ETDEWEB)

Signoret, J.; Imbeaux, F. [Association EURATOM-CEA, CEA / DSM / Institut de Recherche sur la Fusion par confinement Magnetique, CEA-Cadarache, 13 - ST-Paul-Lez-Durance (France)

2009-07-01

The EFDA Integrated Tokamak Modeling Task Force has defined a data structure offering a generic representation of the properties of physics problems and tokamak subsystem characteristics. It gathers the hardware description, modeling results and data measured during experiments, structured in terms of Consistent Physical Objects (CPOs). A generic tool has been developed to retrieve shot-based data from the various European tokamak databases: Exp2ITM. A tokamak specific XML 'mapping file' is used to map the local data formats to the ITM (Integrated Tokamak Modeling) data format. Exp2ITM is then dynamically generated from the ITM data structure and uses generic procedures to import the shot-based data. Successful tests show we have managed to import into the ITM DB experimental data from Jet and Tore-Supra. This document is a poster. (authors)

Generic two-qubit photonic gates implemented by number-resolving photodetection

International Nuclear Information System (INIS)

Uskov, Dmitry B.; Smith, A. Matthew; Kaplan, Lev

2010-01-01

We combine numerical optimization techniques [Uskov et al., Phys. Rev. A 79, 042326 (2009)] with symmetries of the Weyl chamber to obtain optimal implementations of generic linear-optical Knill-Laflamme-Milburn-type two-qubit entangling gates. We find that while any two-qubit controlled-U gate, including controlled-NOT (CNOT) and controlled-sign gates, can be implemented using only two ancilla resources with a success probability S>0.05, a generic SU(4) operation requires three unentangled ancilla photons, with success S>0.0063. Specifically, we obtain a maximal success probability close to 0.0072 for the B gate. We show that single-shot implementation of a generic SU(4) gate offers more than an order of magnitude increase in the success probability and a two-fold reduction in overhead ancilla resources compared to standard triple-CNOT and double-B gate decompositions.

The global biopharma industry and the rise of Indian drug multinationals: implications for Australian generics policy.

Science.gov (United States)

Löfgren, Hans

2007-06-01

This article provides a synopsis of the new dynamics of the global biopharma industry. The emergence of global generics companies with capabilities approximating those of 'big pharma' has accelerated the blurring of boundaries between the innovator and generics sectors. Biotechnology-based products form a large and growing segment of prescription drug markets and regulatory pathways for biogenerics are imminent. Indian biopharma multinationals with large-scale efficient manufacturing plants and growing R&D capabilities are now major suppliers of Active Pharmaceutical Ingredients (APIs) and generic drugs across both developed and developing countries. In response to generic competition, innovator companies employ a range of life cycle management techniques, including the launch of 'authorised generics'. The generics segment in Australia will see high growth rates in coming years but the prospect for local manufacturing is bleak. The availability of cheap generics in international markets has put pressure on Pharmaceutical Benefits Scheme (PBS) pricing arrangements, and a new policy direction was announced in November 2006. Lower generics prices will have a negative impact on some incumbent suppliers but industrial renewal policies for the medicines industry in Australia are better focused on higher value R&D activities and niche manufacturing of sophisticated products.

Has the increase in the availability of generic drugs lowered the ...

African Journals Online (AJOL)

Comparison of price ratios between the originator drug, lowest priced generic and international reference price values revealed that the originator drug prices had a median price ratio of 20.99 (interquartile range 7.31e53.46) and the lowest priced generics had a median price ratio of 4.28 (interquartile range 2.10e8.47).

Aging Management Guideline for commercial nuclear power plants: Power and distribution transformers

International Nuclear Information System (INIS)

Toman, G.; Gazdzinski, R.

1994-05-01

This Aging Management Guideline (AMG) provides recommended methods for effective detection and mitigation of age-related degradation mechanisms in power and distribution transformers important to license renewal in commercial nuclear power plants. The intent of this AMG to assist plant maintenance and operations personnel in maximizing the safe, useful life of these components. It also supports the documentation of effective aging management programs required under the License Renewal Rule 10 CFR Part 54. This AMG is presented in a manner which allows personnel responsible for performance analysis and maintenance to compare their plant-specific aging mechanisms (expected or already experienced) and aging management program activities to the more generic results and recommendations presented herein

Generic versus brand-name drugs used in cardiovascular diseases.

Science.gov (United States)

Manzoli, Lamberto; Flacco, Maria Elena; Boccia, Stefania; D'Andrea, Elvira; Panic, Nikola; Marzuillo, Carolina; Siliquini, Roberta; Ricciardi, Walter; Villari, Paolo; Ioannidis, John P A

2016-04-01

This meta-analysis aimed to compare the efficacy and adverse events, either serious or mild/moderate, of all generic versus brand-name cardiovascular medicines. We searched randomized trials in MEDLINE, Scopus, EMBASE, Cochrane Controlled Clinical Trial Register, and ClinicalTrials.gov (last update December 1, 2014). Attempts were made to contact the investigators of all potentially eligible trials. Two investigators independently extracted and analyzed soft (including systolic blood pressure, LDL cholesterol, and others) and hard efficacy outcomes (including major cardiovascular adverse events and death), minor/moderate and serious adverse events. We included 74 randomized trials; 53 reported ≥1 efficacy outcome (overall sample 3051), 32 measured mild/moderate adverse events (n = 2407), and 51 evaluated serious adverse events (n = 2892). We included trials assessing ACE inhibitors (n = 12), anticoagulants (n = 5), antiplatelet agents (n = 17), beta-blockers (n = 11), calcium channel blockers (n = 7); diuretics (n = 13); statins (n = 6); and others (n = 3). For both soft and hard efficacy outcomes, 100 % of the trials showed non-significant differences between generic and brand-name drugs. The aggregate effect size was 0.01 (95 % CI -0.05; 0.08) for soft outcomes; -0.06 (-0.71; 0.59) for hard outcomes. All but two trials showed non-significant differences in mild/moderate adverse events, and aggregate effect size was 0.07 (-0.06; 0.20). Comparable results were observed for each drug class and in each stratified meta-analysis. Overall, 8 serious possibly drug-related adverse events were reported: 5/2074 subjects on generics; 3/2076 subjects on brand-name drugs (OR 1.69; 95 % CI 0.40-7.20). This meta-analysis strengthens the evidence for clinical equivalence between brand-name and generic cardiovascular drugs. Physicians could be reassured about prescribing generic cardiovascular drugs, and health care organization about endorsing their wider

A model-based framework for design of intensified enzyme-based processes

DEFF Research Database (Denmark)

Román-Martinez, Alicia

This thesis presents a generic and systematic model-based framework to design intensified enzyme-based processes. The development of the presented methodology was motivated by the needs of the bio-based industry for a more systematic approach to achieve intensification in its production plants...... in enzyme-based processes which have found significant application in the pharmaceutical, food, and renewable fuels sector. The framework uses model-based strategies for (bio)-chemical process design and optimization, including the use of a superstructure to generate all potential reaction......(s)-separation(s) options according to a desired performance criteria and a generic mathematical model represented by the superstructure to derive the specific models corresponding to a specific process option. In principle, three methods of intensification of bioprocess are considered in this thesis: 1. enzymatic one...

Dynamic competition in pharmaceuticals. Patent expiry, generic penetration, and industry structure.

Science.gov (United States)

Magazzini, Laura; Pammolli, Fabio; Riccaboni, Massimo

2004-06-01

This paper investigates patterns of industrial dynamics and competition in the pharmaceutical industry, with particular reference to the consequences of patent expiry in different countries. We focus on the competition at the level of single chemical entities, distinguishing between original brands and generic products. Quarterly data, spanning from July 1987 to December 1998, on sales of pharmaceutical products in four countries (USA, UK, Germany, and France) constitute the basis of our analysis. All the products containing major molecules whose patent expiration date lies between 1986 and 1996 are included in our sample. We show how diffusion of generics is linked to the characteristics of the market and investigate how price dynamics of original products are affected by generic competition. Our empirical investigation shows that the dynamics of drug prices and the competition by generic drugs vary significantly across countries. This heterogeneity notwithstanding, a clear distinction seems to emerge. On the one hand, systems that rely on market-based competition in pharmaceuticals promote a clear distinction between firms that act as innovators and firms that act as imitators after patent expiry. Here, original products enjoy premium prices and exclusivity profits under patent protection, and face fierce price competition after patent expiry. On the other hand, in systems that rely on administered prices, penetration by generic drugs tends to be rather limited. Its descriptive and preliminary nature notwithstanding, our analysis seems to have relevant implications at different levels of generality, especially for Europe.

Canada's New Generic Pricing Policy: A Reasoned Approach to a Challenging Problem.

Science.gov (United States)

Hollis, Aidan; Grootendorst, Paul

2015-08-01

Alberta, quickly followed by other Canadian provinces, has introduced a new pricing model for generic drugs, in which prices are inversely related to the number of generic manufacturers of the drug. This paper examines the rationale for the new policy. Copyright © 2015 Longwoods Publishing.

Are generic and brand-name statins clinically equivalent? Evidence from a real data-base.

Science.gov (United States)

Corrao, Giovanni; Soranna, Davide; Arfè, Andrea; Casula, Manuela; Tragni, Elena; Merlino, Luca; Mancia, Giuseppe; Catapano, Alberico L

2014-10-01

Use of generic drugs can help contain drug spending. However, there is concern among patients and physicians that generic drugs may be clinically inferior to brand-name ones. This study aimed to compare patients treated with generic and brand-name statins in terms of therapeutic interruption and cardiovascular (CV) outcomes. 13,799 beneficiaries of the health care system of Lombardy, Italy, aged 40 years or older who were newly treated with generic or brand-name simvastatin during 2008, were followed until 2011 for the occurrence of two outcomes: 1) therapeutic discontinuation and 2) hospitalization for CV events. Hazard ratios (HR) associated with use of generic or brand-name at starting therapy (intention-to-treat analysis) and during follow-up (as-treated analysis) were estimated by fitting proportional hazard Cox models. A Monte-Carlo sensitivity analysis was performed to account for unmeasured confounders. Patients who started on generic did not experience a different risk of discontinuation (HR: 0.98; 95% CI 0.94 to 1.02) nor of CV outcomes (HR: 0.98; 95% CI 0.79 to 1.22) from those starting on brand-name. Patients who spent >75% of time of follow-up with statin available on generics did not experience a different risk of discontinuation (HR: 0.94; 95% CI 0.87 to 1.01), nor of CV outcomes (HR: 1.06; 95% CI 0.83 to 1.34), compared with those who mainly or only used brand-name statin. Our findings do not support the notion that in the real world clinical practice brand-name statins are superior to generics for keeping therapy and preventing CV outcomes. Copyright © 2014. Published by Elsevier B.V.

Aging Management Guideline for commercial nuclear power plants: Motor control centers

International Nuclear Information System (INIS)

Toman, G.; Gazdzinski, R.; O'Hearn, E.

1994-02-01

This Aging Management Guideline (AMG) provides recommended methods for effective detection and mitigation of age-related degradation mechanisms in Boiling Water Reactor (BWR) and Pressurized Water Reactor (PWR) commercial nuclear power plant motor control centers important to license renewal. The intent of this AMG is to assist plant maintenance and operations personnel in maximizing the safe, useful life of these components. It also supports the documentation of effective aging management programs required under the License Renewal Rule 10 CFR Part 54. This AMG is presented in a manner that allows personnel responsible for performance analysis and maintenance to compare their plant-specific aging mechanisms (expected or already experienced) and aging management program activities to the more generic results and recommendations presented herein

Seventeenth symposium on biotechnology for fuels and chemicals. Program and abstracts

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-05-01

This volume contains the abstracts of oral and poster presentations made at the Seventeenth Symposium on Biotechnology for Fuels and Chemicals. Session titles include Thermal, Chemical, and Biological Processing; Applied Biological Research; Bioprocessing Research; Special Topics Discussion Groups; Process Economics and Commercialization; and Environmental Biotechnology.

Towards a Generic Information Data Model for Verification, Validation & Accreditation VV&A

NARCIS (Netherlands)

Roza, Z.C.; Voogd, J.M.; Giannoulis, C.

2008-01-01

The Generic Methodology for Verification, Validation and Acceptance (GM-VV) is intended to provide a common generic framework for making formal and well balanced acceptance decisions on a specific usage of models, simulations and data. GM-VV will offer the international M&S community with a

Deeply discounted medications: Implications of generic prescription drug wars.

Science.gov (United States)

Czechowski, Jessica L; Tjia, Jennifer; Triller, Darren M