Dissertations / Theses on the topic 'Blood products Quality control'

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The present work is grounded basically on the use of the Basic Tools for the Statistic Process Control SPC, with the intent to detect non-conformities on a given productive process. It consists on a case study accomplished at a Hemocenter in Natal (Rio Grande do Norte). In this study it is shown that, the Statistic Process Control Technique, which was used as a tool, is useful to identify on-conformities on the volume of hemocomponents. The gathering of the used data was performed by means of document analysis, direct observations and database queries. The results achieved from the study show that the analyzed products, even though when they have presented, in some cases, points out of control, they satisfied the ANVISA standards. Finally, suggestions for further improvement of the final product and guidance for future employment of CEP, also extended to other lines of production, are presented
A presente disserta??o fundamenta-se, basicamente, na utiliza??o das Ferramentas B?sicas do Controle Estat?stico do Processo CEP, com o objetivo de detectar n?o conformidades num determinado processo produtivo. Trata-se de um estudo de caso, realizado em um Hemocentro, no munic?pio de Natal (Rio Grande do Norte). Demonstra-se no estudo que a t?cnica do controle estat?stico do processo, utilizada como ferramenta, ? ?til para identificar n?o conformidades no volume dos hemocomponentes. A coleta dos dados utilizados se deu atrav?s de: an?lise documental, observa??es diretas e consultas ao banco de dados. Os resultados do estudo demonstram que os produtos analisados, mesmo apresentando, em alguns casos, pontos fora de controle, satisfaziam as normas da ANVISA. Finalmente, s?o apresentadas sugest?es para melhorar ainda mais o produto final e tamb?m orientar a futura implanta??o do CEP, inclusive em outras linhas de produ??o

Most complementary medicines contain a multitude of chemical components, some of which are claimed to contribute to the biological activity of such products. Use of complementary medicines for preventative and therapeutic purposes is increasing rapidly worldwide. Unfortunately, although control of these products is essential to ensure quality, safety, and efficacy, the quality control of most herbal preparations is currently poor to non-existent, with little or no safety and efficacy data required to support the marketing and use of these products. The objective of this study was therefore to develop suitable analytical methods to qualitatively and quantitatively analyse the relevant components (rutin, isoquercitrin, hyperoside, quercitrin, quercetin, kaempferol, hypericin, pseudohypericin and hyperforin) in St John's Wort dosage forms for quality control purposes. A gradient HPLC method using a Luna 5·mC₁₈(2) 150 x 2.00mm internal diameter (i.d.) column and UV detection, was developed for the separation of six of the relevant flavonoid compounds in St John's Wort, namely rutin, isoquercitrin, hyperoside, quercitrin, quercetin and kaempferol. The development process involved a systematic investigation of gradient conditions, flow rate, and temperature. This method was subsequently applied to assay selected commercially available St John's Wort products. This system provided the necessary accuracy, precision and reproducibility and was associated with several advantages when compared to using standard bore (4.60 mm i.d.) HPLC columns. The method developed is currently the only known method that separates all six relevant flavonoids in a reasonable run time (less than 20 minutes). It is also one of the few methods that has sufficient separation between rutin, isoquercitrin and hyperoside. A qualitative method for the fingerprinting of flavonoid components was also developed, using capillary electrophoresis (CE). CE is a rapidly growing powerful analytical technique for the separation of charged compounds. Micellar electrokinetic chromatography (MEKC) is a very powerful electrophoretic technique that is capable of selectively resolving both neutral and ionic solutes in a single run. A MEKC method suitable for the separation and determination of various flavonoid constituents used as marker compounds in Hypericum perforatum was developed. Investigations into the effect of pH, ionic strength, applied voltage and capillary dimensions on separation were performed. The optimised method was then applied to qualitatively analyse various St John's Wort products on the market. This method was found to be advantageous in that it was simple, cost-effective, required minimal sample preparation and utilised very small quantities of sample. Due to the vast differences in chemical properties between the various marker and active components in St John's Wort, it was necessary to develop separate analytical methods for the flavonoids and for the other three relevant compounds (hypericin, pseudohypericin and hyperforin). An isocratic HPLC method using a Luna 5·mC₁₈(2) 150 x 2.00mm (i.d.) column and UV detection was developed for the separation of hypericin, pseudohypericin and hyperforin. The development process involved a systematic investigation of buffer molarity, mobile phase composition, pH, flow rate, and temperature. This method was subsequently applied to assay selected commercially available St John's Wort products on the South African market. This system also provided the necessary accuracy, precision and reproducibility, as well as the advantages associated with the use of a narrow bore column as opposed to the use of the more commonly used wider bore columns. This method was validated and used to quantitate these three compounds in various commercial St John's Wort products. By applying this method to liquid chromatography – tandem mass spectrometry (LC-MS-MS), qualitative analyses of the same products was performed to obtain confirmation of the quantitative HPLC results. Mass spectrometry is a powerful detection tool that is more selective and specific than many detection systems used with HPLC. Natural medicines usually constitute a multitude of constituents with much potential interference. In this regard LC-MS-MS is a powerful tool, with its ability to unequivocally identify target analytes regardless of the presence of interferences or complex matrices. ESI-MS-MS was used for the qualitative analysis of the content of the naphthodianthrones and hyperforin in the respective tablet products assayed with HPLC. LC-MS-MS analyses were performed in order to identify the constituents and to verify the specificity of the HPLC method. High inter-product and inter-batch variability was observed for all nine compounds assayed. These quantitative results were confirmed with the respective qualitative analyses. This study confirms the need for strict quality control of herbal medicinal products commercially available to consumers.

Cloud top height plays an important roll in the energy budget and is also important for aviation. This thesis concerns the quality control of cloud top height (CTH) retrievals. The approach for quality controlling retrieved CTH has been using the forward simulating software RTTOV. An error estimation function has been developed as well as an investigation to what simplifications can be done regarding the forward simulations for CTH purposes at SMHI. The purpose of the error estimation function is to validate CTH output from CTH retrieval algorithms by giving a rough error estimate of the retrieved CTH compared to what forward simulations predict. For simplifying the forward simulations the most promising results have been shown for lower clouds. Further testing is still of interest and for future work suggestions are provided regarding the error estimation function as well as for simplifying the forward simulations.

In many business sectors today, the focus on quality as a competitive tool is being replaced by a focus on innovation. Research exploring connections between quality management, innovation, and company performance suggests that quality is 'necessary but insufficient' in today's business environment. In short, the question facing managers, particularly those in small firms, is how to adapt their quality management practices to achieve innovation performance in addition to quality performance. To answer this question, West Coast U.S. forest products manufacturers were surveyed about quality management practices and performance with respect to both quality and innovation. Quality management practices were assessed following the systems perspective articulated by the Malcolm Baldrige National Quality Award. Data envelopment analysis was used to identify companies efficiently using quality management practices to lead to quality and/or innovation performance. Survey responses from the efficient firms were then analyzed via cluster analysis to identify two categories of firms: those achieving primarily quality outcomes and those achieving both quality and innovation outcomes. Executives from two firms in each category were interviewed to provide detail on the management practices used by the companies. Interview transcripts were examined to identify similarities and differences in practices between the two categories of firms. Results suggest several specific areas of focus for firms wanting to adapt their quality management practices to achieve both quality and innovation performance. For example, firms focused on innovation proactively seek to identify and meet customers' needs whereas quality-focused firms primarily emphasize reacting to customer complaints. More specifically with respect to 'customer focus', firms focused on innovation emphasize convenience for their customers through practices such as standardizing product lines and providing product specifications on their websites. In contrast, neither quality-focused firm had a website. These firms were at their production capacity (at least prior to the recession) and viewed websites strictly as a means to attract new business rather than as a service to existing customers. Also with regards to customer focus, firms focused on innovation sought to generate new business - not just for their company, but for their customers as well. Beyond customer focus, firms focused on innovation provide employees with opportunities to help the organization implement changes. With respect to benchmarking, firms focused on innovation actively sought to measure their performance against the 'best practice' in the industry; firms focused primarily on quality performance demonstrated little if any emphasis on benchmarking. Finally, there were apparent overarching and hence cultural differences between the two categories of firms - firms focused on innovation were more proactive, strategic, and willing to take risk; in addition, these firms discussed innovation as the means to improve product quality, reduce costs, or attract new customers. By contrast, the quality-focused firms were reactive, conservative, and risk-averse; these firms discussed innovation primarily as 'technology' without reference to potential linkages to company performance.

Hong Kong's aging population has, increased demand for vascular services. Currently, vascular surgery is subsumed under general surgery. The workload on both general surgery and vascular surgery is demanding and hence, not conductive to the development of vascular surgery. The volume of surgery, particularly emergency surgery provided by the Hospital Authority units varies significantly. The collaboration and differentiation of labor at present is not well defined in many centers. This may lead to unnecessary competition and duplication of resources in the long run. This project examined if there is room for improvement in the present situation and provides evidence for relevant service reconfiguration and discusses how Hong Kong can learn from some overseas examples to enhance quality of services delivered to patients.
published_or_final_version
Public Health
Master
Master of Public Health

Thesis (Ph. D.)--Missouri University of Science and Technology, 2008.
Vita. The entire thesis text is included in file. Title from title screen of thesis/dissertation PDF file (viewed March 2, 2009) Includes bibliographical references (p. 216-220).

El control microbiològic és essencial en la indústria farmacèutica ja que es tracta d’un indicador de la seguretat dels productes. Els mètodes microbiològics utilitzats a les companyies farmacèutiques per analitzar l’ambient del procés de fabricació així com els productes finals estan basats en mètodes de cultiu tradicional. La tecnologia d’aquests mètodes manca de precisió comparada amb les tecnologies més modernes de detecció i identificació microbiològica. Cada vegada, els requeriments dels controls microbiològics de productes i processos són més estrictes, el que fa que es necessiten mètodes cada vegada més ràpids i precisos. Dintre d’aquest context s’han desenvolupat els mètodes de microbiologia ràpida (RMM) per a la seva implantació a la industria farmacèutica, avalada per les diferents agències reguladores. Les diferents tecnologies en les quals es basen els RMM es coneixen a l’àmbit acadèmic des de fa dècades, no obstant la seva implantació i validació a les indústries farmacèutiques és relativament recent. La implementació de noves metodologies a l’àmbit farmacèutic està regulada per la normativa de bones practiques de fabricació (BPF), el qual va associat a una adequada validació de les tècniques. Aquesta tesi descriu la implementació de RMM al control microbiològic del procés de fabricació i productes a l’empresa Laboratoris Reig Jofré (RJF). El principal objectiu ha estat dividit en 3 blocs individuals: implementació d’un programa d’identificació microbiana per als aïllats del procés de fabricació i productes; implementació d’un mètode de detecció de microorganismes a l’aire de sales classificades per fabricació asèptica basat en fluorescència induïda per làser i l’ avaluació d’un sistema basat en citometria en fase sòlida per la detecció de microorganismes en productes filtrables. En general, els RMM implementats han contribuit a obtenir resultats de manera més ràpida, el qual permet mitigar el risc de contaminació en el mateix moment que ha sigut detectat. Aquest projecte assenta les bases per futures aplicacions de RMM en el procés de fabricació farmacèutica.
Microbiological testing plays an essential role in the Pharmaceutical Industry as it is an indicator of safety in drug products. The microbiological methods used in the pharmaceutical companies for testing the environment of the manufacturing process as well as the final products are based on traditional culture methods. These methods, although being appropriate for their intended use, rely on century-old technology that lacks accuracy when compared to most up-to-date methodologies for microbial detection and identification. Every time the requirement of microbiological testing of products and processes increases, arising the need of faster and more accurate methods. In this paradigm, rapid microbiological methods (RMM) are developed for their implementation in the pharmaceutical industry encouraged by regulatory agencies. The different technologies in which rapid microbiological methods are based have been known in the academic field for decades, however their implementation and validation in the pharmaceutical industries is relatively recent. Implementation of new methodologies in a pharmaceutical environment ruled under Good Manufacturing Practice (GMP) guidelines needs proper validation of the techniques involved. This thesis describes the implementation of RMM in the microbial monitoring of the pharmaceutical manufacturing process and products in Reig Jofré Laboratories (RJF). The main objective has been divided into three different blocks: implementation of a microbial identification program for the isolates found in the production process and products; implementation of a laser-induced fluorescence system for the detection of airborne microorganisms in cleanrooms for aseptic processing and evaluation of a solid-phase cytometry system for the detection of microorganisms in filterable products. In general, the RMM implemented have contributed to obtain faster results which allows to mitigate contamination risk at the moment it is detected. This projects lays the ground for further applications of RMM in the pharmaceutical manufacturing process.

The shortage in water resources have been observed all over the world. However, the safety of drinking water has been given much attention by scientists because the disinfection will react with organic matters in drinking water to generate disinfection by-products (DBPs) which are considered as the cancerigenic matters. Although much research has been carried out on the water quality control problem in DWDS, the water quality model considered is linear with only chlorine dynamics. Compared to the linear water quality model, the nonlinear water quality model considers the interaction between chlorine and DBPs dynamics. The thesis proposes a nonlinear model predictive controller which utilises the newly derived nonlinear water quality model as a control alternative for controlling water quality. EPANET and EPANET-MSN are simulators utilised for modelling in the developed nonlinear MPC controller. Uncertainty is not considered in these simulators. This thesis proposes the bounded PPM in a form of multi-input multi-output to robustly bound parameters of chlorine and DBPs jointly and to robustly predict water quality control outputs for quality control purpose. The methodologies and algorithms developed in this thesis are verified by applying extended case studies to the example DWDS. The simulation results are presented and critically analysed.

The objective of the study was to determine the effects of Aloe ferox inclusion in drinking water on growth performance, blood biochemistry, physico-chemical characteristics, fatty acid profile and oxidative stability of broiler meat. The importance of A. ferox as a medicinal plant and factors that influence its utilization by communal poultry farmers were also investigated by use of a questionnaire survey. The survey revealed that the majority of respondents (84.6%) faced health challenges in their chickens and many relied (96.2%) on A. ferox to treat diseases and control parasites. The study also revealed that the choice of medicine (traditional or conventional) was influenced (P<0.05) by level of education and income. In the second phase of the research, a total of 600 Ross 308 day-old broilers, were randomly put in 6 treatment groups with 4 replicates, each having 25 birds. Fresh aqueous A. ferox leaf juice (ALJ) was administered in drinking water at a dosage of 20ml/litre to T1, T2 and T3 from day one to day 35, day one to day 14 and day 15 to day 28, respectively. Birds in T4 and T5 (positive controls) were treated with terramycin at the recommended dosage of 14g/litre of drinking water from day one to day 6 and from day 15 to 20, respectively; and birds in T6 (negative control) received distilled water from day 1 to 35. Feed Intake (FI), average daily gain (ADG) and feed conversion ratio (FCR) were calculated for the 5 week trial. After slaughter, carcass characteristics particularly dressing percentage (DP) and relative organ weight (ROW) were calculated. Serum biochemistry was also determined. For meat quality, pH and color were recorded 45 minutes and 24 hours after slaughter from the breast muscle. Fatty acid profiling and oxidative stability were determined using meat samples from the breast and thigh muscles. The results for growth performance showed that thebirds which were given A. ferox for the first two weeks (T2) consumed significantly (P>0.05) more feed (189.4g) than those in the negative control (159.6g) at the beginning of the starter phase. Subsequently, their ADG recorded on day 7 (27.1g) and day 14 (43.1g) were significantly (P<0.05) higher than the negative control (22.8g and 36.2g, respectively). Significant treatment effects (P<0.05) for FCR were reported in the 4th week for the birds that received A. ferox throughout (T1: 3.5). Carcass characteristics were not significantly (P>0.05) affected by A. ferox inclusion in drinking water. The highest high density lipoprotein (HDL) values (2.78 mmol/L) were yielded in T2and T3 had the lowest values (0.61mmol/L) for low density lipoprotein (LDL). For physico-chemical properties, no significant effects (P>0.05) of treatment on pH, colour, cooking loss and tenderness were observed. However, the group treated with A.ferox throughout the production cycle, had the highest pH (6.2), lowest lightness (38.5), highest redness (4.1), highest tenderness (13.86N) and the lowest cooking loss (12.6%). Significant treatment effects (P<0.05) were observed on the composition of the PUFA eicosatrienoic acid (C20:3c8, 11, 14(n-6)) of the breast muscle which was significantly lower in the A. ferox treatment groups than the positive controls. For the thigh muscle, there were significant (P<0.05) treatment effects on composition of palmitoleic acid (C16:1c9) and g-linolenic acid (C18:3c6, 9, 12 (n-3)). No significant (P>0.05) effects were found on oxidative stability of both thigh and breast muscles. In conclusion, the wide use of A. ferox by communal chicken farmers showed its importance as a medicinal plant. Apart from it being an effective medicinal plant, A. ferox inclusion in drinking water results in improved FI, ADG, reduced in LDLC and better g-linolenic and palmitoleic acid composition in the meat.

Thesis (MScMed)--Stellenbosch University, 2008.
ENGLISH ABSTRACT: Introduction: Flow cytometry has progressively replaced many traditional laboratory tests due to its greater accuracy, sensitivity and rapidity in the routine clinical settings especially clinical trails. It is a powerful tool for the measuring of chemical (the fluorochrome we add) and physical (size and complexity) characteristics of individual cells. As these instruments became major diagnostic and prognostic tools, the need for more advanced quality control, standardized procedures and proficiency testing programs increased as these instrumentations and their methodology evolve. Minor instrument settings can affect the reliability, reproducibility and sensitivity of the cytometer and should be monitored and documented in order to ensure identical conditions of measurement on a daily basis. This can be accomplished by following an Internal Quality Assurance (IQA) and/ or External Quality Assurance (EQA) program. Currently there are no such programs available in South Africa and poorer Africa countries. HIV is a global concern and the laboratories and clinics in these places are in need of such IQA programs to ensure quality of their instrumentation and accurate patient results. Quality assurance programs such as CD Chex® and UK Nequas are available but due to bad sample transport, leave the receiving laboratories with nightmares. It would be best if there was a laboratory in South Africa that could provide the surrounding laboratories with stabilized whole blood samples that can be utilized as IQA. The transport of these samples can be more efficient due to shorter distance and thus the temperature variations limited. Aims and Objectives: The aim of Chapter one is to familiarize the reader with general terminology and concepts of immunology. Chapter two describes in detail the impact stabilized whole blood had on clinical immunology concerning Quality Control and Quality Assurance. The objective of this study is to stabilize whole blood with a shelf life of greater than 30 days to serve as reference control material for South African Immunophenotyping. It is further an objective to use these in-house stabilized control samples for poorer African countries as Internal Quality Assurance reference material. It is a still further objective to stimulate various lymphocyte subsets to express activation antigens and then stabilize these cells for more specialized immunological test and can serve as a QC for those required samples. Study design: In Chapter three, the method currently used to stabilize whole blood was modified. The stability of different concentrations of a first stabilizing agent (Chromium Chloride hexahydrate) was investigated. Incubation periods and concentrations of paraformaldehyde as second stabilizing agent were investigated. Blood samples from healthy individuals (n=10) were stabilized and monitored for the routine HIV phenotypic surface antigens over a period of 40 days. These samples (n=10) were compared on the Becton Dickinson Biosciences (BD) FACSCalibur™ versus BD FACSCount™ instrumentation. Blood samples (n=3) were stabilized and monitored to identify phenotypic cell surface molecules for as long as possible. They were quantified on both flow cytrometric instruments. In addition, these stabilized samples (n=3) were investigated as control blood for calibration purposes on the BD FACSCount™ instrument. In Chapter four, lymphocytes were isolated and activated with various stimuli to express sufficient activation antigens such as CD25, CD69, HLA-DR and CD40 Ligand on the T helper cell surfaces. These activated antigens were analyzed on the BD FACSCalibur™ and further stabilized to serve as possible IQA samples in future. Results: In Chapter three, the ten individual stabilized samples had non-significant P values (P > 0.05) for CD3, CD4 and CD8 percentages and absolute values comparing day 3 until day 40. Comparing the BD FACSCalibur™ versus BD FACSCount™, resulted in a R2 = 0.9848 for CD4 absolute values and a R2 = 0.9636 for CD8 absolute values. Stabilized blood samples (n=3) were monitored for routine HIV phenotypic markers until day 84. The cells populations were easily identifiable and could be quantified on both BD FACSCalibur™ and BD FACSCount™ instruments. In Chapter four; for the activation study purposes, activated T helper lymphocytes expressed approximately 25 to 35% CD40 Ligand cell surface molecules. The stimulant of choice was Ionomycin at a 4μM concentration. Cells were incubated for four hours at 37 degree Celsius in a 5% CO2 environment. For CD69 surface expression, 6 hour incubation was optimum. The stimulus of choice in this case was 4μM Ionomycin which induced 84.21% CD69 expression in the test samples. For CD25 expression; 6 hour incubation with PHA resulted in approximately 43% of CD25 expression. For HLA-DR surface expression; 6 hour incubation with PHA resulted in approximately 43.32% of HLA-DR expression. Activated lymphocytes expressing CD40 Ligand showed stability until day 23. Activated Lymphocytes expressing CD69, CD25 and HLA-DR were stabilized in the same manner and stability could be achieved until day 16. Conclusion: This thesis was related to the preparation of control samples (IQA) designed to simulate whole blood having defined properties in clinical laboratory situations. In future kits can be developed with a low, medium and high control sample for the various immunological phenotypic determinants. Another kit can be compiled where various activation markers can be identified, quantified with a “zero”, low and high control. These whole blood IQA kits and “activation IQA kits” can be implemented for training of newly qualified staff, competency testing of staff, method development, software testing, panel settings and instrument setting testing. Control samples ideally must have a number of properties in order to be effective. For instance stability during storage times, preferably lasting more than a few weeks, reproducibility and ease of handling. These will provide the information on day-to-day variation of the technique or equipment which will enhance accuracy and improve patient care.
AFRIKAANSE OPSOMMING: Inleiding: Vloeisitometrie tegnologie het verskeie tradisionele laboratorium toetse vervang as gevolg van beter akuraadheid, sensitiwiteit en vinniger beskikbaarheid van resultate in ‘n kliniese omgewing, veral kliniese proewe. Vloeisitometrie is ‘n kragtige tegniek om chemiese (fluorokroom byvoeging) en fisiese (sel grote en kompleksiteit) karakter eienskappe van individuele selle te meet. Met die toename in gebruik en gewildheid van hiedie instrumente, neem die behoefde toe vir gevorderde kwaliteit kontroles, gestandardiseerde prosedures, met profesionele toets programme tesame met metode ontwikkeling. Klein verstellings aan instrument parameters beinvloed die betroubaarheid, herhaalbaarheid en sensitiwiteit van ‘n sitometer en moet gemonitor (en dokumenteer) word om identiese kondisies van leesings op ‘n daaglikse basis te verseker. Dit kan bereik word deur in te skakel met ‘n interne kwaliteits versekerings program [IQA: “Internal Quality Control”] en/of ‘n eksterne kwaliteits versekerings program [EQA: “External Quality Control”] te volg. Op die oomblik is daar geen sulke kwaliteits versekerings programme in Suid Afrika en/of in die verarmende Afrika lande beskikbaar nie. MIV is ‘n wêreldwye bekommernis en laboratoriums en klinieke in hierdie gedeeltes van die land verlang ‘n dringende behoefdte vir sulke “IQA” programme om kwaliteit van instrumentasie en akkurate pasiënt resultate te verseker wat tot beter behandeling van pasiënte lei. Kwaliteit versekerings programme soos “CD Chex®” en “UK Nequas” is beskikbaar, maar baie probleme met verwysing na monster integriteit as gevolg van tydsame vervoer en aflewering kondisies word hiermee geassosieër. Die behoefte het ontstaan vir ‘n laboratorium in Suid Afrika wat direk die omliggende laboratoriums, hospitale en klinieke kan voorsien met gestabiliseerde blood monsters wat gebruik kan word as “IQA”. Die vervoer en aflewerings kondisies van hierdie monsters sal aansienlik verbeter as gevolg van die korter aflewerings afstand wat direk die beperkte temperatuur wisseling beinvloed. Doel van studie: Die doelwit van hoofstuk een is om vir die leser ‘n inleiding te gee tot terminologie en konsepte van immunologie en die immune sisteem. Hoofstuk twee beskyf die impak wat gestabiliseerde heelbloed het op die kliniese immunologie met betrekking tot kwaliteit beheer en kwaliteit versekering. Die doelwit van hierdie studie is om heelbloed te stabiliseer sodat die rakleeftyd meer as 30 dae is en sodoende as verwysings-materiaal kontroles vir Suid Afrikaanse immunofenotipering kan dien. Dit is ‘n verdere doelwit om hierdie tuis-gestabiliseerde kontrole monsters te gebruik as “IQA” verwysings materiaal in verarmende Afrika lande. Die doelwit van hoofstuk vier is om limfosiete te stimuleer om verskeie aktiverings merkers uit te druk op hul selmembrane en dan te stabiliseer en dié te gebruik as Kwaliteits Kontroles vir die meer gespesialiseerde immunologiese toetse. Studie ontwerp: Hoofstuk drie beskryf ‘n aangepaste en verbeterde metode van heel bloed stabiliseering. Stabiliteit word ondersoek in ‘n verskyndenheid konsentrasies van ‘n primêre stabiliseerings agent (chromium chloried heksahidraat) en inkubasie periodes met paraformaldehied as tweede stabiliseerings agent word deeglik gedokumenteer. Bloedmonsters van gesonde indiwidië (n=10) was gestabiliseer en gemonitor vir roetine MIV membraanoppervlak antigene oor ‘n periode van 40 dae. Hierdie monsters (n=10) was gelees en geanaliseer op ‘n BD FACSCalibur™ en vergelyk met ‘n BD FACSCount™ vloeisitometer instrument. Drie gestabiliseerde heelbloed monsters (n=3) was gemonitor vir ‘n periode vir so lank moontlik die fenotipiese selmembraan molekules identifiseerbaar was en die kwantiteit bepaalbaar was. Hierdie drie monsters was gemeet op beide instrumente. As ‘n addisionele doelwit, was hierdie drie gestabiliseerde monsters ondersoek om as moontlike kalibrasie materiaal (verteenwoordig ‘n normale bloedmonster) te dien vir die BD FACSCount™ instrument in die oggende voor pasiënt monsters gelees kan word. In hoofstuk vier was limfosiete geϊsoleer en geaktiveer met ‘n verskyndenheid stimulante om optimale aktiveerings-antigene uit te druk op T helper selmembrane (byvoorbeeld CD25, CD69, HLA-DR en CD40 Ligand). Hierdie geaktiveerde monsters was geanaliseer op die BD FACSCalibur™ en daarna gestabiliseer. Na stabilisasie van die geaktiveerde limfosiet monsters was dit gemonitor oor ‘n tydperk so lank moontlik data plotte leesbaar en selpopulasies identifiseerbaar was. Hierdie monsters kan dien as ‘n moontlike “IQA” toets stel vir ‘n meer gespesialiseerde immunologiese aktiveerings kontrole doeleindes. Resultate: In hoofstuk drie; tien individiële gestabiliseerde heelbloed monsters het gedui op geen-beduidende P waardes (P > 0.05) vir CD3, CD4 en CD8 persentasies en absolute waardes; gemeet vanaf DAG 3 vergelykbaar tot-en-met DAG 40. Met korrelasie statistiek en vergelyking van die BD FACSCalibur™ met die FACSCount™ instrumente, is die volgende opgemerk; R2 = 0.9848 vir die CD4 absolute waardes en ‘n R2 = 0.9636 vir die CD8 absolute waardes. Drie gestabiliseerde monsters (n=3) was gemonitor vir MIV roetine fenotipeering tot en met DAG 84. Die selpopulasies was duidelik identifiseerbaar en die kwantitatief meetbaar op albei instrumente (BD FACSCalibur™ en BD FACSCount™). Hoofstuk vier: geaktiveerde T helper lymphosiete het 25 – 35% membraan CD40 Ligand uitgedruk op hul selmembrane. Die stimulant van keuse was ionomysien teen ‘n optimale konsentrasie van 4μM. Die optimale inkubasie tydperk was vier ure by 37°C in 5% CO2 kondisie. Ses uur inkubasie in 4μM ionomysien by 37°C in ‘n 5% CO2 omgewing was optimal vir die CD69 selmembraan uitdrukking en het 84.21% opgelewer. Vir CD25 selmembraan uitdrukking was die selle vir ses ure met phietoheamagglutinin (PHA) gestimuleer by 37°C in 5% CO2 kondisie en het 43% CD25 selmembraan uitdrukking opgelewer. HLA-DR selmembraan uitdrukking: selle was vir ses ure saam met PHA by 37°C in 5% CO2 kondisie inkubeer en het 43.32% opgelewer. CD40 Ligand aktivering/gestabiliseerde limfosiete het tot en met dag 23 stabiliteit getoon. Die ligand was duidelik identifiseerbaar en kwantifiseerbaar. Geaktiveerde lymphosiete wat CD69, CD25 en HLA-DR selmembraan merkers uitdruk het na die stabiliseerings proses stabiliteit getoon tot-en-met dag 16. Gevolgtrekking: Die doel van hierdie studie was om verwysingskontroles voor te berei sodat dit vars heelbloed naboots met uitkenbare eienskappe vir kliniese situasies. ‘n Toets kontrolestel met verwysings materiaal vir drie vlakke (byvoorbeeld ‘n lae, medium en hoë kontrole) absolute selwaardes en persentasies kan voorberei word vir roetine immunologiese fenotiperings merkers (CD3/CD4/CD8/CD45). Meer gespesialiseerde kontrolestelle vir meer spesifieke doeleindes kan opgemaak word wat ‘n verskydenheid van limfosiet aktiveringsmerkers bevat met byvoorbeeld ‘n “nul”, lae en hoë verwysings kontrole daarin. Hierdie heelbloed kan dien as “aktiveerde interne kwaliteits verwysings materiaal” en kan gebruik word om nuut aangestelde laboratorium werkers en nuut gekwalifiseerde studente op te lei. Hierdie verwysings materiaal / kontroles kan aangewend word vir bevoegdheids doeleindes (byvoorbeeld vir SANAS akkreditasie doeleindes), vir metode ontwikkeling, vir sagteware toetsing, vir paneel opstelling en instrument verstellings doeleindes. Die kontroles moet ‘n verskydenheid eienskappe bevat om effektief te wees. Byvoorbeeld, stabiliteit tydens storing, gewenslik meer as ‘n paar weke, herhaalbaar en maklik handteerbaar. Hierdie kontroles sal inligting voorsien op ‘n daaglikse basis tydens wisseling van tegnieke of instrumentasie wat akuraatheid beinvloed en op die ou-end direk pasiënt versorging bevoordeel.

Quality control of herbals has its roots in the study of morphoanatomic and organoleptic characters. Nevertheless, in the last century, with the evolution of analytical chemistry, the quality control rapidly evolved from elementary tests to the use of sophisticated instruments combined with software for data management. In the current days, many authorities and organizations recommend a suite of tests, featuring many of these instruments, to evaluate quality of herbal products. HPTLC offers a comprehensive set of data that can be used not only for identification but also to evaluate the purity and content of herbal drugs, herbal preparations, and herbal products. The objective of this doctoral thesis was to explore in-depth the capacities of HPTLC and develop applications for quality control of herbals, far beyond simple identification of the herbal drugs, preparations, and products. For that, five studies were developed. In the first study, the quality of herbal drugs, preparations, and products from milk thistle fruit, coneflower root and aerial parts and black cohosh root, regulated under food supplements or medicines were evaluated with existing HPTLC methods. The suitability of these methods, using the entire fingerprint and several detection modes, as a tool for detecting quality problems, mainly adulterations, was confirmed. In the second study, the comprehensive HPTLC fingerprinting concept was developed with the goal of simplifying the quality control process. This concept combines the qualitative and quantitative information of HPTLC images, obtained in a single analysis, to evaluate the identity, purity and content of herbals. The possibilities of applying it to identify an herbal drug, detect mixtures with re¬lated species (purity), and develop a minimum content test of an analytical marker were demonstrated in Angelica gigas root. In the third study, the application of comprehensive HPTLC fingerprinting aimed to go one step beyond in the test for adulterants and to evaluate the use of the HPTLC for purity limit tests. This approach was evaluated with sam¬ples of ginkgo leaf and extracts, commercialized as food supplements in different countries. This study demonstrated that the information contained in the HPTLC finger¬prints was suitable for verifying levels of rutin and quercetin, providing results similar to that of the HPLC limit test. It was also useful for detecting mixtures of ginkgo products not only with rutin and quercetin but also with buckwheat herb and sophora (flower bud or fruit). In the fourth study, it was evaluated the use of comprehensive HPTLC fingerprinting as an alternative method to the current HPLC assay of markers of TCM drugs in the Ph. Eur. The goal of this project was to simplify the determination of content and thus reducing the number of tests to be performed during quality control. For this evaluation, two TCM herbal drugs were chosen by the experts of the TCM working party of the Ph. Eur.: Fritillaria thunbergii bulbs and corydalis rhizome. In both cases, comprehensive HPTLC fingerprinting was proven useful for identification and minimum content testing in one single analysis. The fifth study goes one step beyond in the content determination. While the previous studies focused in the quantification of single markers, this study aimed to apply comprehensive HPTLC fingerprinting to quantify a group of constituents in an herbal drug, as an example of a more holistic assessment of quality. This determination was combined with the tests for purity and identity. To illustrate this concept, Ganoderma lucidum fruiting body was chosen. In this work, HPTLC proved to be a useful technique for routine quality control of herbal drugs, preparations and products. As demonstrated, it can simplify this process by applying the concept of comprehensive HPTLC fingerprinting. A detailed guideline of how to develop, validate and apply comprehensive HPTLC fingerprinting methods for routine quality control of herbals has been elaborated and is also included in the thesis.
El control de qualitat dels productes a base de plantes té les seves arrels en l'estudi dels caràcters morfoanatòmics i organolèptics. No obstant això, al segle passat, amb l'evolució de la química analítica, el control de qualitat va evolucionar ràpidament des de proves elementals a l'ús d'instruments sofisticats combinats amb programari per a la gestió de dades. Actualment, moltes autoritats i organitzacions recomanen un conjunt de proves, amb molts d'aquests instruments, per avaluar la qualitat dels productes a base de plantes. La HPTLC ofereix un conjunt complet de dades que poden usar-se no només per a la identificació, sinó també per avaluar la puresa i el contingut de drogues i preparats vegetals i productes a base de plantes. L'objectiu d'aquesta tesi doctoral va ser explorar en profunditat les capacitats de la HPTLC i desenvolupar aplicacions per al control de qualitat dels productes de plantes medicinals, molt més enllà de la simple identificació de drogues i preparats vegetals i productes acabats comercialitzats. Per això, es van desenvolupar cinc estudis. En el primer estudi, es va avaluar la qualitat de les drogues vegetals, preparats vegetals i productes a base de plantes del fruit de card marià, l'arrel i la part aèria de equinàcia i l'arrel de cimicífuga, regulats com complements alimentosos o medicaments, amb els mètodes existents de HPTLC. Es va confirmar la idoneïtat d'aquests mètodes, utilitzant l'empremta dactilar completa i diversos formes de detecció, com una eina per a detectar problemes de qualitat, principalment adulteracions. En el segon estudi, es va desenvolupar el concepte d'anàlisi integral de l'empremta dactilar per HPTLC (comprehensive HPTLC fingerprinting) amb l'objectiu de simplificar el procés de control de qualitat. Aquest concepte combina la informació qualitativa i quantitativa de les imatges d’HPTLC, obtingudes en una única anàlisi, per avaluar la identitat, la puresa i el contingut dels productes a base de plantes. La seva aplicabilitat per identificar una droga vegetal, detectar mescles amb espècies relacionades (puresa) i desenvolupar un assaig de contingut mínim d'un marcador analític es van demostrar en l'arrel d'Angelica gigas. En el tercer estudi, l'aplicació de l'anàlisi integral de l'empremta dactilar per HPTLC va tenir com a objectiu anar un pas més enllà en l'assaig de adulterants i avaluar l'ús de l’HPTLC per a l'assaig límit de puresa. Aquest enfocament es va avaluar amb mostres de fulla i extracte de ginkgo, comercialitzats com a complements alimentosos en diferents països. Aquest estudi va demostrar que la informació continguda en les empremtes dactilars per HPTLC era adequada per verificar els nivells de rutina i quercetina, proporcionant resultats similars als de l'assaig límit per HPLC. També va ser útil per detectar mescles de productes de ginkgo no només amb rutina i quercetina, sinó també amb part aèria de blat sarraí i sòfora (botó floral i fruit). En el quart estudi, es va avaluar l'ús de l'anàlisi integral de l'empremta dactilar per HPTLC com un mètode alternatiu a l'actual valoració de marcadors per HPLC en drogues vegetals de la medicina tradicional xinesa (MTC) a la Ph. Eur. L'objectiu d'aquest projecte era simplificar la determinació del contingut i, per tant, reduir el nombre de proves a realitzar durant el control de qualitat. Per a aquesta avaluació, dues drogues vegetals de la MTC van ser elegides pels experts del grup de treball TCM de la Ph. Eur.: bulb de Fritillaria thunbergii i rizoma de coridalis. En tots dos casos, es va demostrar que l'empremta dactilar completa per HPTLC era útil per a la identificació i l'assaig de contingut mínim en una sola anàlisi. El cinquè estudi va un pas més enllà en la determinació del contingut. Si bé els estudis anteriors es van centrar en la quantificació de marcadors individuals, aquest estudi va tenir com a objectiu aplicar l'anàlisi integral de l'empremta dactilar per HPTLC a la quantificació d'un grup de components en una droga vegetal, com un exemple d'una avaluació més holística de la qualitat. Aquesta determinació es va combinar amb els assajos d'identitat i puresa. Per il·lustrar aquest concepte, es va triar el carpòfor de Ganoderma lucidum. En aquest treball, s'ha demostrat que la HPTLC és una tècnica útil per al control de qualitat rutinari de drogues i preparats vegetals i productes a base de plantes, i que es pot simplificar aquest procés aplicant el concepte d'anàlisi integral de l'empremta dactilar per HPTLC. S'ha elaborat una guia detallada (inclosa a la tesi) sobre com desenvolupar, validar i aplicar mètodes d'anàlisi integral de l'empremta dactilar per HPTLC per al control de qualitat rutinari de productes a base de plantes.
El control de calidad de los productos a base de plantas tiene sus raíces en el estudio de los caracteres morfoanatómicos y organolépticos. Sin embargo, en el siglo pasado, con la evolución de la química analítica, el control de calidad evolucionó rápidamente de las pruebas elementales al uso de instrumentos sofisticados combinados con software para la gestión de datos. Actualmente, muchas autoridades y organizaciones recomiendan un conjunto de pruebas, con muchos de estos instrumentos, para evaluar la calidad de los productos a base de plantas. La HPTLC ofrece un conjunto completo de datos que pueden usarse no sólo para la identificación, sino también para evaluar la pureza y el contenido de drogas y preparados vegetales y productos a base de plantas. El objetivo de esta tesis doctoral fue explorar en profundidad las capacidades de HPTLC y desarrollar aplicaciones para el control de calidad de los productos de plantas medicinales, mucho más allá de la simple identificación de drogas vegetales, preparados vegetales y productos finales comercializados. Para eso, se desarrollaron cinco estudios. En el primer estudio, se evaluó la calidad de las drogas vegetales, preparados vegetales y productos a base de plantas del fruto del cardo mariano, la raíz y la parte aérea de equinácea y la raíz de cimicífuga, regulados como complementos alimenticios o medicamentos, con los métodos existentes de HPTLC. Se confirmó la idoneidad de estos métodos, utilizando la huella digital completa y varios modos de detección, como una herramienta para detectar problemas de calidad, principalmente adulteraciones. En el segundo estudio, se desarrolló el concepto de análisis integral de la huella dactilar por HPTLC (comprehensive HPTLC fingerprinting) con el objetivo de simplificar el proceso de control de calidad. Este concepto combina la información cualitativa y cuantitativa de las imágenes de HPTLC, obtenidas en un único análisis, para evaluar la identidad, la pureza y el contenido de los productos a base de plantas. Su aplicabilidad para identificar una droga vegetal, detectar mezclas con especies relacionadas (pureza) y desarrollar un ensayo de contenido mínimo de un marcador analítico se demostraron en la raíz de Angelica gigas. En el tercer estudio, la aplicación del análisis integral de la huella dactilar por HPTLC tuvo como objetivo ir un paso más allá en el ensayo de adulterantes y evaluar el uso de la HPTLC para el ensayo límite de pureza. Este enfoque se evaluó con muestras de hoja y extracto de ginkgo, comercializados como complementos alimenticios en diferentes países. Este estudio demostró que la información contenida en las huellas dactilares por HPTLC era adecuada para verificar los niveles de rutina y quercetina, proporcionando resultados similares a los del ensayo límite por HPLC. También fue útil para detectar mezclas de productos de ginkgo no sólo con rutina y quercetina, sino también con parte aérea de trigo sarraceno y sófora (botón floral y fruto). En el cuarto estudio, se evaluó el uso del análisis integral de la huella dactilar por HPTLC como un método alternativo a la actual valoración de marcadores por HPLC en drogas vegetales de la medicina tradicional china (MTC) en la Ph. Eur. El objetivo de este proyecto era simplificar la determinación del contenido y, por lo tanto, reducir el número de pruebas a realizar durante el control de calidad. Para esta evaluación, dos drogas vegetales de la MTC fueron elegidas por los expertos del grupo de trabajo TCM de la Ph. Eur.: bulbo de Fritillaria thunbergii y rizoma coridalis. En ambos casos, se demostró que la huella digital completa de HPTLC era útil para la identificación y el ensayo de contenido mínimo en un solo análisis. El quinto estudio va un paso más allá en la determinación del contenido. Si bien los estudios anteriores se centraron en la cuantificación de marcadores individuales, este estudio tuvo como objetivo aplicar el análisis integral de la huella dactilar por HPTLC a la cuantificación de un grupo de componentes en una droga vegetal, como un ejemplo de una evaluación más holística de la calidad. Esta determinación se combinó con los ensayos de identidad y pureza. Para ilustrar este concepto, se eligió el carpóforo de Ganoderma lucidum. En este trabajo, se ha demostrado que la HPTLC es una técnica útil para el control de calidad rutinario de drogas y preparados vegetales y productos a base de plantas, y que se puede simplificar este proceso aplicando el concepto de análisis integral de la huella dactilar por HPTLC. Se ha elaborado una guía detallada (incluida en la tesis) sobre cómo desarrollar, validar y aplicar métodos de análisis integral de la huella dactilar por HPTLC para el control de calidad rutinario de productos a base de plantas.

The purpose of the study is to evaluate the service quality that the SANBS provides to its customers, by measuring customers’ perceptions and their expectations of service quality provided by the supplier of blood transfusion services. The organization that is used for this study is the South African National Blood Service (SANBS). Specifically the study seeks to: 1. Determine the extent to which customers are satisfied or not satisfied with the service they receive from the SANBS using the ten-dimensional format of SERVQUAL model, modified to the specific service quality requirements of the blood transfusion service industry. 2. Establish customers’ perceptions of the service they receive using a multiple-item scale (SERVQUAL) for measuring consumer perceptions of service quality. 3. Establish customers’ expectations of the service, and compare them to their perceptions of the service they currently receive. The comparison is made along each service quality dimension, across different parts of same service on a geographical basis, and across different customer groups on a customer category (or type) basis. 4. Recommend implementation of appropriate service quality performance improvement procedures where necessary. Study design and methods: The data for the study came from the SANBS’ customer perception and expectation survey conducted in 2005. Questionnaires were sent out to hospitals that use products and services provided by the SANBS in the Eastern Cape and KwaZulu-Natal Provinces of South Africa. The questionnaire was based on the multiple-item SERVQUAL model for measuring consumer perceptions of service quality, modified and tailored to specific service quality requirements of the blood transfusion service industry. Questionnaires were sent out to 113 (69.3%) hospitals out of a total of 163 blood-utilizing hospitals in the two provinces. Of the 113 hospitals, 92 (81.4%) responded, with questionnaires rendered unusable. The final sample size is 88 and is included in the final study database. The data is analyzed by comparing different parts of the service on a geographical basis namely KwaZulu-Natal and Eastern Cape zones. The data is also analyzed by comparing different customer groups namely the Rural State Hospitals, the Urban State Hospitals and Private Hospitals. Results: The result confirms the research (alternative) hypothesis (H1 : μ1 ≠ μ2), and rejects Ho. The overall expectations ratings are higher than the perceptions ratings, and the KwaZulu-Natal expectations ratings are higher than the Eastern Cape ratings. The expectations of private hospitals and rural state hospitals have a higher rating than that of urban state hospitals and the perceptions of private and urban state hospitals have a higher rating than that of rural state hospitals. The largest service quality gap is the accessibility dimension which relates specifically to approachability and ease with which customers can access staff at different levels of the organization by e-mail, and includes accessing of knowledgeable blood bank personnel and medical staff of SANBS, but may also relate to the distance of hospitals from the nearest blood bank, all of which are situated in urban state hospitals. The mean difference for accessibility is the highest followed by the understanding customer mean difference. The mean differences for the other dimension categories are significantly less than that of the largest two dimensions, but not significantly different amongst themselves. The mean difference for rural state hospitals is the largest followed by private hospitals and urban state hospitals. The mean difference for rural state hospitals is greater than that for urban state hospitals in both zones, but the mean difference for private hospitals is greater in KwaZulu-Natal than in the Eastern Cape. The dimension means of differences for rural state hospitals are greater than that for urban state hospitals. According to the correlations between expectations and perceptions for different dimensions, there is a weak or no linear relationship between expectations and perceptions. Conclusion: This empirical study supports the literature on the provision of service quality, and concludes that there is a statistically significant difference or gap between the services offered by the SANBS as perceived by its customers, and the expectations of its customers. The study substantiates the need for management of blood transfusion services to take into account customer perceptions of service quality and their expectations, and upon identification of gaps, to implement appropriate service quality improvement processes, rather than take a one sided view of their (SANBS’) own perception of service quality.

Esta tesis describe la aplicación de la aproximación de Calidad por Diseño para el desarrollo y cualificación del proceso de liofilización de dos productos farmacéuticos, denominados IFDA e IFDB, desarrollados en la empresa Laboratorios Reig Jofre. IDFA está formado por un único principio activo, y se presenta en dos dosificaciones, mientras que IDFB es más complejo ya que, además del principio activo, contiene un excipiente. El proceso de liofilización se utiliza para transformar disoluciones de principios activos en productos sólidos más estables. Es un proceso lento y costoso, por lo tanto, su optimización es una prioridad en la industria farmacéutica. La liofilización se divide en tres etapas: congelación, secado primario o sublimación, y secado secundario o desorción. El secado primario es generalmente la etapa más larga y está relacionada con un mayor riesgo para la calidad del producto. Por lo tanto, la mayor parte de los esfuerzos se centraron en su optimización. En primer lugar, se definió la huella dactilar térmica de cada formulación, utilizando un conjunto de técnicas analíticas, como calorimetría de barrido diferencial, microscopía de liofilización o difracción de rayos X. A continuación, se estudió la influencia de la temperatura de la bandeja y la presión de la cámara sobre los atributos de calidad del producto y la eficiencia del proceso mediante un diseño experimental tipo Doehlert, estableciendo finalmente el espacio de diseño del secado primario a escala laboratorio. Las condiciones operativas del proceso industrial se seleccionaron centrándose en la reducción del tiempo de proceso a la vez que se preservaba la calidad del producto. Posteriormente, el proceso se transfirió y cualificó a escala industrial, y se confirmó que todos los lotes cumplían con las especificaciones de calidad del producto después de 12 meses de estabilidad, siguiendo las recomendaciones de la guía ICH Q1A(R2). Durante la cualificación del proceso de liofilización, se requirió un muestreo extensivo para garantizar la homogeneidad del secado. Este gran número de muestras no puede analizarse de manera efectiva mediante el método convencional de Karl Fischer. En consecuencia, se desarrolló y validó un método de espectroscopia de infrarrojo cercano (NIR del inglés near infrared) para la determinación del contenido de humedad residual en las dos dosis del producto liofilizado IFDA de manera no destructiva y rápida. La viabilidad del uso de la espectroscopia NIR para la predicción de la humedad residual en viales liofilizados se evaluó utilizando herramientas de análisis de riesgos y estudios de mitigación de riesgos. Se creó un único modelo útil para las dos dosis del producto IFDA, con el objetivo final de obtener el modelo más simple y robusto con una capacidad predictiva aceptable. Durante la validación del método, se prestó especial atención a la estimación del límite de detección y se propuso un enfoque de cálculo útil para el caso estudiado. Finalmente, el modelo NIR se aplicó para realizar un mapeo de humedad de dos liofilizadores industriales y para evaluar su posible aplicación para analizar muestras sometidas a diferentes condiciones de almacenamiento.
This thesis describes the application of Quality by Design for the development and qualification of the freeze-drying process of two drug products, named IFDA and IFDB, developed in Laboratorios Reig Jofre. IDFA is composed by an Active Principle Ingredient (API), and it is presented in two different strengths, while IDFB is more complex since, in addition to the API, it contains an excipient. The freeze-drying process is used to transform solutions of active ingredients in more stable solid products. It is a time-consuming and expensive process; hence a successful development and optimization is a priority in the pharmaceutical industry. This process is divided in three stages: freezing, primary drying or sublimation and secondary drying or desorption. The freeze-drying process optimization was focused on the primary drying, since it is usually the longest stage and it is generally related with the highest impact to product quality. First, characterization studies of both formulations were performed to define their thermal fingerprint using a variety of analytical techniques, such as differential scanning calorimetry, freeze-drying microscopy or X-ray powder diffraction. Then, the influence of primary drying shelf temperature and chamber pressure on product quality attributes and process efficiency was studied through a Doehlert design, and the design space was established at lab-scale. The process operational conditions for production manufacturing were selected focusing on process time reduction while preserving the quality of the product. Afterwards, the process was scale-up and qualified at industrial scale, and it was confirmed that all batches complied with product quality specifications after 12 month of ICH stability studies. During freeze-drying qualification, extensive sampling was needed to guarantee the homogeneity of the drying process. This large number of samples cannot be effectively analysed by the conventional Karl Fischer method. Consequently, a non-destructive and fast near infrared spectroscopy (NIRS) method was developed and validated for residual moisture content determination in the two strengths of IFDA drug product. The feasibility of using near infrared spectroscopy for the intended purpose was assessed using risk analysis tools and risk mitigation studies. A single model useful for two strengths of the injectable freeze-dried product was built up, with the final aim of obtaining the most simple and robust model with an acceptable predictive ability. During method validation, special attention was placed in the estimation of the limit of detection and a calculation approach was proposed. Finally, this NIRS model was applied to perform a moisture mapping of two industrial freeze-dryers, and to evaluate the potential application of the NIRS method to analyse samples subjected to different storage conditions.

Thesis (Ph. D.)--Electrical and Computer Engineering, Georgia Institute of Technology, 2005.
Dr. Jennifer E. Michaels, Committee Chair ; Dr. Bonnie Heck Ferri, Committee Member ; Dr. George J. Vachtsevanos, Committee Member ; Dr. Magnus Egerstedt, Committee Member ; Dr. Farrokh, Ayazi, Committee Member ; Dr. Sheldon M. Jeter, Committee Member. Vita. Includes bibliographical references.

A própolis é uma resina de coloração e consistência variada coletada por abelhas da espécie Apis Mellifera de diversas partes da planta como brotos, botões florais e exsudados resinosos, sendo transportados para a colméia com a finalidade de defesa e vem se destacando por suas atividades terapêuticas, como atividade antimicrobiana, antiinflamatória, cicatrizante, anticaríogênica e anticancerígena. Estudos realizados com a própolis brasileira mostraram a presença de muitos compostos fenólicos, sendo o mais recente, a identificação de derivados prenilados do ácido cumárico. Dentre estes, o mais estudado é o ácido 3,5-diprenil-4hidroxicinâmico (Artepillin-C), separada da própolis produzida em áreas cuja flora é rica em espécies de Baccharis. A sua quantificação tem se tornado um fator importante como indicador da qualidade da própolis brasileira. O objetivo deste estudo foi o desenvolvimento e a validação do método de determinação de Artepillin-C, assim como a caracterização e quantificação dos principais parâmetros relacionados ao controle de qualidade da própolis preconizada pela legislação brasileira vigente, foram realizadas análise de: umidade, cinzas, teor de cera, teor de massa mecânica, teor de sólidos solúveis em etanol, índice de oxidação, f1avonóides totais e fenólicos totais. O trabalho foi complementado com análise polínica e determinação da atividade antioxidante Amostras de própolis foram obtidas de apicultores e entrepostos totalizando 33 amostras procedentes das regiões Nordeste, Centro-Oeste, Sudeste e Sul do Brasil, no período de 2003 a 2005. As amostras de própolis analisadas apresentaram resultados, na quase totalidade, de acordo com os limites estabelecidos pelo Ministério da Agricultura. A maioria das amostras apresentou alta atividade antioxidante inibindo a oxidação da reação acoplada de β-caroteno a ácido linoléico em torno de 86,0%. O método de análise de Artepillin C atendeu a todos os parâmetros preconizados para a validação do método cromatográfico (linearidade, precisão, exatidão, limite de detecção e limite de quantificação) podendo ser recomendado para análise de rotina em laboratórios de controle de qualidade. A análise estatística mostrou uma forte correlação entre os seguintes parâmetros: cinzas e massa mecânica; compostos fenólicos e solúveis em etanol assim como os compostos fenólicos e atividade antioxidante. Também foi constatada uma variação nos valores dos outros parâmetros analisados em função da procedência das amostras de própolis.
Propolis is a resin of varied color and consistency collected by honeybee, Apis Mellifera, from several parts of the plant such as sprouts, f10wer buds and resinous exsudatos, being transported to the hive with the intent of defending and it has become really popular for its therapeutic properties, such as antimicrobial, anti inflammatory, healing anti-carcinogenic and anti-cancerigenous properties. Studies performed with the Brazilian propolis showed the presence of several phenolic compounds, as the most recent brings the identification of prenyl derivative of coumaric acid. Among them, the most studied one is 3,5-diprenyl-4-hydroxycinnamic acid (Artepillin-C), isolated from the propolis produced in areas which flora is rich in Baccharis species. Its quantification has become an important factor as indicator of Brazilian propolis quality. The aim of this study was to develop and validate a method to determine Artepillin-C, as well the identification and quantification of main parameters related to quality control of propolis forecasted in the current Brazilian regulation (moisture, ashes wax content, mechanic matter, content of solid soluble in ethanol, oxidation rate, total f1avonoid and total phenolic).The polinic studies and antioxidant activity determination were also performed to complement this work. Propolis samples were obtained from beekeepers and warehouses summing up 33 samples from the Northeast, Southeast, Mid-West and South of Brazil from 2003 to 2005. The propolis samples studied presented results which were almost all in accordance to the set limits by the Brazilian Agriculture Department. Most samples presented high antioxidant activity preventing oxidation from the coupled reaction of βcarotene to linoleic acid around 86,0%. The analysis method for Artepillin C addressed all the forecasted parameters for the validation o f the chromatographic method (linearity, precision, accuracy, detection limit and quantification limit) as it can be recommended for the routine analysis in labs to control quality. The statistics showed a strong relationship between the following parameters: ashes and mechanic matter; phenolic compounds and soluble in ethanol as well as phenolic compounds and antioxidant activity. It was also observed a variation in the figures for other studied parameters due to the origin of propolis samples.

Thesis (MSc)--University of Stellenbosch, 2005.
ENGLISH ABSTRACT: Pasta manufacturing is a process whereby wheat flour is converted into a shelf-stable food that is more desirable than native wheat flour. It can be fortified and may serve as a valuable source of nutrition in developing countries. Quality measures are of importance in the production process to ensure a consistent and acceptable finished product. Literature provides information on many aspects of wheat types, milling techniques and processing of pasta. Protein content and quality of cultivated wheat varieties is of major importance to produce quality pasta products. Wheat types of lower protein content are more readily available than traditionally used durum wheat. As in all food products, the cost of final products is of major importance. Bread wheat is generally less expensive than durum wheat. However, product quality (and thus acceptability) may be lower. Direct measurements of product quality are currently limited to protein content, moisture content, colour analyses and certain other characteristics measurable in a laboratory, for example mechanical strength and firmness. Direct measurements of defects that may affect final product quality, such as cracks and fissures on the strands of spaghetti, different types of spots and lines on the strands, broken units, units sticking together and odd shapes are not well documented. During the first part of this study, spaghetti quality evaluation techniques were reviewed, improved or developed and thereafter standardised. This developmental research was conducted to establish valid and reliable measures (with a high degree of repeatability) for the evaluation of dry and cooked pasta quality characteristics. A wide variety of available products on the South African market were evaluated for different quality characteristics. From this evaluation standards were drawn up, tested for validity and reliability by means of repeatability. Minimum sample sizes for the evaluation of different quality characteristics were calculated and presented in the study, together with reference photographs that can be used to evaluate spaghetti. This study found that colour evaluation by means of commercially available apparatus needs revision. This study suggests the use of multiple layers when evaluating translucent food products for colour. The occurrence of fissures and flour spots are of importance for the quality of the final product. This study provides a set of valid and reliable measurements for measuring the quality of dry and cooked spaghetti. Simple techniques can therefore be used to detect the presence or absence of these defects. Thereafter an empirical study was conducted to describe the differences between spaghetti prepared from durum and non-durum wheat, dried at different temperatures and at different relative humidity. Spaghetti samples of diverse perceived quality, from different manufacturers, were purchased and evaluated. Standard methods and the newly developed testing methods were used to test whether these methods effectively distinguish between spaghetti of diverse quality, reflecting on the validity of the methods. Correlations were calculated between dependent and independent variables in an attempt to find possible explanations for certain defects or quality differences, and to test certain theories in the literature. Certain relationships between quality characteristics were found, while others were questioned. The most important proven relationships were between protein content and its effects on reducing quality defects such as fissures, breakages and cooking losses. The relationship between ash content and spaghetti colour could not be confirmed in this study. This study confirmed that protein remains one of the most important variables to ensure consistent quality spaghetti.
AFRIKAANSE OPSOMMING: Pastavervaardiging is ‘n proses waartydens koring meel omskep word in a produk met ‘n stabiele en lang rakleeftyd wat meer gewens is as die oorspronklike koring meel. Pasta kan gefortifiseer word and kan dien as a waardevolle voedingsbron in ontwikkelende lande. Om ‘n konstante en aanvaarbaare finale produk te verseker is kwaliteitmetings gedurende die produksie proses belangrik. Die literatuur voorsien heelwat inligting rakende aspekte van belang vir pastakwaliteit, byvoorbeeld koringtipes, maaltegnieke en die vervaardigingsproses. Proteïninhoud en die kwaliteit daarvan is van groot belang tydens die produksie van hoë kwaliteit pasta. Koringtipes met ‘n laer proteïninhoud is meer geredelik beskikbaar as tradisionele durumkoring. Soos met alle voedselprodukte, is die koste van die finale produk van groot belang. Oor die algemeen verhandel broodkoring teen laer pryse as durumkoring. Die produkkwaliteit en aanvaarbaarheid van pasta vervaardig van broodkoring kan egter laer wees as dié van durumkoring. Direkte metings van produkkwalitiet is tans beperk tot proteïninhoud, voginhoud, kleuranalise en sekere eienskappe meetbaar in ‘n laboratorium, byvoorbeeld meganiese sterkte en fermheid. Die direkte meting van defekte wat finale produkkwaliteit kan beïnvloed, byvoorbeeld barste, krake, meel kolletjies, strepe op spaghetti-eenhede, gebreekte eenhede, eenhede wat aan mekaar kleef en ongewone vorms, is nie goed gedokumenteer nie. Gedurende die eerste gedeelte van hierdie studie, is ‘n oorsig van spaghetti evaluasie tegnieke beskikbaar in die literatuur gdoen, waarna sekeres verbeter is, ander ontwikkel is en finaal gestandariseer is. Hierdie navorsing is uitgevoer om geldige en betroubare metings (met ‘n hoë graad van herhaalbaarheid) vir die evaluasie van droë- en gaar pastakwalitietseienskappe vas te stel. ‘n Wye verskeidenheid van produkte beskikbaar op die Suid-Afrikaanse mark is ge-evalueer ten opsigte van verskillende kwaliteitseienskappe. Vanuit hierdie evaluasies is standaarde saamgestel en getoets vir geldigheid en betroubaarheid deur middel van herhaalbaarheid. ‘n Minimum steekproefgrootte per kwaliteitseienskap is bereken en word vermeld in hierdie studie. Daarmeesaam word verwysingsfoto’s aangebied wat gebruik kan word tydens die evaluasie van spaghetti. Hierdie studie bied a stel geldige en betroubare meting vir die kwaliteit van droe en gaan spaghetti. Eenvoudige tegnieke kan dus gebruik word om die voorkoms van hierdie defekte te meet. Met afloop van die verkennende studie, is ‘n empiriese studie gedoen om die verskille te beskryf tussen pasta vervaardig van durum en brood koring, gedroog teen verskillende temperature en relatiewe humiditeit. Spaghettimonsters met oënskynlike diverse kwaliteit, vervaardig deur verskillende maatskappye, is aangekoop en ge-evalueer. Standaardmetings en nuutontwerpte metings is gebruik om te bevestig of die metings kan onderskei tussen spaghetti met uiteenlopende kwaliteit, wat reflekteer op die geldigheid van die metingsmetodes. Korrelasies is bereken tussen afhanklike en onafhanklike veranderlikes in ‘n poging om moontlike verklarings vir sekere defekte of kwaliteitsverskille te vind, en ook om sekere teoriëe in die literatuur te toets. Die verband tussen sekere kwaliteitseienskappe is bevestig en bewys, terwyl ander bevraagteken was. Die mees belangrike verband was proteïninhoud en die effek daarvan om die voorkoms van defekte, soos barste, gebreekte eenhede en kookverliese te verlaag. Die verband tussen asinhoud en spaghettikleur kon nie in hierdie studie bevestig word nie. Hierdie studie het bevestig dat proteïn die mees belangrike veranderlike is wat oorweeg moet word wanneer ‘n konstante hoë kwaliteit spaghettiproduk vervaardig word. Kleurevaluasie met behulp van kommersieel-beskikbare apparaat vereis hersiening. Hierdie studie stel voor dat tydens kleur evaluasie van voedsel wat lig deurlaatbaar is, dit in veelvoudige lae evalueer moet word. Die voorkoms van defekte soos barste, krake of meel kolletjies is van belang ten opsigte van finale produkkwaliteit. Hierdie studie bied riglyne vir die evaluasie van die genoemde defekte. Die voorkoms van hierdie defekte is van groter belang as die graad waarteen die defek voorkom. Eenvoudige tegnieke kan vervolgens gebruik word om die teenwoordigheid of afwesigheid van hierdie defekte te bepaal.

Élaboration de deux stratégies de "détection-localisation" de défauts dans les signaux issus du contrôle par courants de Foulcault des produits sidérurgiques. Validation de ces stratégies dans le contrôle qualité de trois procédés : élaboration de brames de coulée continue, élaboration de blooms de coulée continue et de tubes

Currently cellular therapies, such as hematopoietic stem cell transplantation (HSCT), are produced at a small scale on a case-by-case basis, usually in a clinical or near-clinical setting. Meeting the demand for future cellular therapies will require a robust and scalable manufacturing process that is either designed around or controls the variation associated with biological starting materials. Understanding variation requires both a measure of the allowable variation (that does not negatively affect patient outcome) and the achievable variation (with current technology). The prevalence of HSCT makes it an ideal case study to prepare for more complex biological manufacturing with more challenging regulatory classifications.

Thesis (MBA)--Stellenbosch University, 2003.
ENGLISH ABSTRACT: With globalisation and the accompanying increase in international trade there is a great drive towards performing risk assessments on the quality of products. Such assessments are of particular importance within the food and drug industry, so much that this approach is also being adapted by the FDA in their analysis of the quality of products and probable risks to it. The pharmaceutical industry is heavily regulated to reduce or eliminate the production and distribution of poor quality products. Pharmaceuticals have to be of high quality as people's lives depend on it. Many pharmaceutical companies import raw materials from international manufacturers or international agents. In most cases the raw material or the products have to go through a long and complicated supply chain. The more parties involved in the supply chain, the greater the risk to product quality. Supply chain partnerships have therefore become critical to manage these risks to product quality throughout the supply chain. In order to manage risks to product quality, it has become vital to perform product quality risk assessments, especially through the supply chain. In this study the Failure Mode Effect Analysis (FMEA) is used to perform a risk assessment of risks to product quality throughout the supply chain. To obtain the criticality of the risks the Failure Mode Effect and Criticality Analysis (FMCEA) is applied. Quality improvement systems which contribute towards managing the risks to product quality are also discussed in this report. By managing quality risks to pharmaceutical products along with using quality as a strategy, the pharmaceutical company contributes towards improved health for patients as well as customer satisfaction, business success and excellence.
AFRIKAANSE OPSOMMING: Die toepassing van die analise van die risiko op produkte is vinnig besig om te vermeerder. Die FDA gaan dit toepas in hulle analise van die kwaliteit van produkte en die risiko wat daarmee gepaard gaan, in die voedsel en medisyne bedryf. Die farmaseutiese industrie word baie streng gereguleer om te verhoed dat die produksie en distribusie van swak kwaliteit produkte ervaar word. Farmaseutiese produkte moet van hoë gehalte wees, omdat die gesondheid van pasiënte daarvan afhang. Baie farmaseutiese maatskappye bestel rou materiale van oorsese makelaars en in baie gevalle moet die rou materiale deur 'n lang en gekompliseerde voorsieningsketting gaan. Hoe meer agente betrokke is, hoe hoër word die risiko met respek tot die kwaliteit van die produk. Die voorsieningsketting speel 'n kritiese rol om te verseker dat risikos beheer kan word, omdat elke party verantwoordelik is vir die lewering van kwaliteitsprodukkte. Om te verseker dat risikos beheer word, het dit belangrik geword om risiko analise te doen op die kwaliteit van produkte, veral wanneer in die voorsieningsketting. In hierdie studie word die "Failure Mode Effect Analysis (FMEAJ' gebruik om 'n risiko analise te doen met betrekking tot risikos op 'n produk se kwaliteit wanneer in die voorsieningsketting. Die "Failure Mode Effect, and Criticality Analysis (FMECAJ', word ook toegepas om te bereken hoe krities die risiko is. Verbeteringstelsels wat bydra tot die beheer en kontrole van risikos vir produk kwaliteit word ook in hierdie studie bespreek. Deur die risikos te beheer op die kwaliteit van produkte, dra die farmaseutiese maatskappy by tot beter gesondheid vir pasiente, en verseker klient satisfaksie en suksesvolle besigheid.

Um die Qualität von Blutprodukten nach GMP zu überprüfen, wurden 72 Blutspenden bzw. ihre Folgeprodukte Erythrozytenkonzentrat in PAGGS-M, gefiltertes Erythrozytenkonzentrat und Fresh Frozen Plasma untersucht. Zusätzlich wurden an jeweils 12 Blutderivaten, die z.T. nicht zum Routineprogramm des Blutspendedienstes der Abteilung für Klinische Hämostaseologie und Transfusionsmedizin in Homburg/Saar gehören, Messungen durchgeführt, um ihre Qualität am Herstellungstag und am Ende der Haltbarkeit zu bestimmen. Als letztes wurden schließlich auch rheologische Parameter an 21 Erythrozytenkonzentraten in PAGGS-M und Fresh Frozen Plasma über einen Zeitraum von 28 Tagen gemessen und dokumentiert. Die Messung der Parameter, sowohl hämatologische als auch hämostaseologische und hämorheologische, erfolgte nach Standardmethoden. Die Ergebnisse waren insgesamt nicht zufriedenstellend. Ausschlaggebende Grundlage der Untersuchung sind die GMP-Richtlinien, die sich an den europäischen Normen orientieren. Zwar zeigten die Produkte, die routinemäßig hergestellt werden, wie auch die, die nur für diese Untersuchung produziert wurden, in vielen Bereichen ein Übereinstimmen mit den Vorschriften. Speziell auch die Qualität der gefilterten Erythrozytenkonzentrate, die besonders für Immunsupprimierte wegen ihres niedrigen Gehalts an Leukozyten verwendet werden, war in vielen Fällen gut. Die Ergebnisse der rheologischen Messungen glichen denen anderer Studien: so wurde ein Abfall der Fließfähigkeit über den Meßzeitraum hinweg beobachtet, was auf ein leichtes Schwellen der Zellen und eine Zunahme der Rigidität zurückzuführen ist. Fast durchgängig wich der Meßwert für den Hämatokrit der EK von der Richtlinie ab, am stärksten in PAGGS-M. Als Grund hierfür wurde eine Meßungenauigkeit des elektronischen Zellzählers bzw. die Methode der Bestimmung angesehen, so daß eine echte Abweichung als unwahrscheinlich anzusehen ist. Jedoch wurde die vorgeschriebene maximale Hämolyserate mit Ablauf der Haltbarkeit häufig überschritten, ebenso wie die gemessenen Leukozytenzahlen. Eine Vielzahl der Plasmen war durch Erythrozyten und Leukozyten kontaminiert. Durch häufige Waschvorgänge beim Auftauen von tiefgefrorenen EK wurde ein erhöhter Hb-Überstand erzeugt, das geforderte Mindestvolumen wurde dabei unterschritten. Daher ist festzuhalten, daß für jede untersuchte Produktgruppe Abweichungen festgestellt wurden, die in diesem Maße nicht tolerabel sind. Damit ist die Qualität der Produkte insgesamt als unzureichend zu bezeichnen. Der hier geführte Nachweis dieser Abweichungen ermöglichte die Einführung geänderter Herstellungsverfahren, so daß die heute erzeugten Produkte den Qualitätsvorschriften entsprechen.
72 blood donations and their follow-up products (red blood cell concentrates resuspended in PAGGS-M, leukocyte-reduced red cell concentrates and fresh frozen plasma) were investigated to check their quality. Additionally, tests were performed on blood components of which most were not part of the routine program in the Department of Hemostaseology and Transfusion Medicine in Homburg/Saar. Finally, rheological parameters of red blood cell concentrates in PAGGS-M and of fresh frozen plasma were measured and documented over a period of 28 days. The results were not satisfying. Both the routine products and the blood components which were only produced for this study met the GMP-guidelines in many cases. Especially the quality of leukocyte-reduced red blood cell concentrates which are used especially for the transfusion for immunocompromised patients was good. The results of the rheological measurements were similar to those of other studies: decreasing flow over a period of time which was put down to slight swelling of the cells and to a rise in erythrocyte rigidity. The average hematokrit of red cell concentrates was generally too low especially in PAGGS-M. The reason for this was thought to be the electronic cell counter or rather the method of measuring. Hemolysis after storage and mean leucocyte count often exceeded the official dates. Many samples of the FFP were contaminated with red and white blood cells. Repeated washing after thawing of frozen red blood cell concentrates caused an excess of extracellular haemoglobin and low concentrate volumes. Any deviation from the guidelines is not tolerable. After this study adjustments in the production could be made so blood products now meet all of the requirements.

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A Coordenação Geral de Sangue e Hemoderivados CGSH, do Ministério da Saúde, comprometida com a missão de elaborar políticas que promovam o acesso da população à atenção hematológica e hemoterápica de forma segura e com qualidade, desenvolve suas ações em consonância com os princípios e as diretrizes do Sistema Único de Saúde – SUS e através da ANVISA implantou em 2001 a Avaliação Externa da Qualidade em Imuno-hematologia (AEQIH) contando com 8 unidades produtoras (UP). Em 2005 o Hemocentro de Botucatu passou a integrar as UP. Este trabalho tem como objetivo avaliar o desempenho dos serviços de hemoterapia (SH) da área de abrangência da Grande São Paulo, sob responsabilidade da UP de Botucatu no período de 2005-2015 levando em consideração diferentes indicadores: número de serviços atendidos/índice de adesão; erros e acertos nas técnicas de tipagem ABO e RhD, pesquisa de anticorpos irregulares (PAI), identificação de anticorpos irregulares (IAI), teste da antiglobulina direta (TAD), prova cruzada (PC) e fenotipagem eritrocitária (FE). A análise estatística realizada foi a de regressão linear, teste de correlação de Spearman e Curva ROC. Durante os 10 anos foram enviados 29 painéis práticos contendo 4 tipagens ABO e RhD (n=10.382), 2 amostras para PAI, IAI e TAD (n=5.191 respectivamente), PC (n=1.611) e FE (n=1.074) e 21 avaliações teóricas (18.975 questões). A média de SH participantes durante o período determinado foi de 89,5. O índice de crescimento, levando em consideração o número de serviços avaliados em 2005 e aqueles em 2015, indica um crescimento de 26,6%. Quanto à avaliação dos painéis práticos, o desempenho dos indicadores avaliados foi: ABO> RhD> PC>TAD>PAI>IAI>FE. Na avaliação individual o desempenho dos indicadores avaliados foi: IAI>PAI>FE>PC>ABO>TAD>RhD. Foram identificados 28 SH com o pior desempenho em mais de um parâmetro avaliado (24,13% do total): dos sete parâmetros avaliados, erraram dois deles (71%), três (11%), quatro (14%) e cinco (4%). O teste de correlação de Spearman identificou que o pior desempenho prático tem relação com o perfil dos serviços que não executam determinadas técnicas, bem como aqueles que têm dificuldade de responder a questionários. O percentual geral de acertos da avaliação teórica não apresenta tendência de resultados estáveis. O percentual individual de acertos da avaliação teórica varia de 80% a 99,9%.
The General Coordination of Blood and Hemoderivatives, of the Ministry of Health, committed to the mission of developing policies that promote the population's access to hematological and hemotherapeutic care in a safe and quality way, develops its actions in accordance with the principles and guidelines Of the Unified Health System and through ANVISA implemented in 2001 the External Evaluation of Quality in Immunohematology with 8 production units (PU). In 2005 the Botucatu Blood Transfusion Center became part of the UP. This study aims to evaluate the performance of hemotherapy services (HS) in the Greater São Paulo area, under the responsibility of the PU of Botucatu in the period 2005-2015, taking into account different indicators: number of services attended / rate of adherence; Errors in ABO and RhD typing techniques, irregular antibody test (IAT), identification of irregular antibodies (IAI), direct antiglobulin test (DAT), cross-test (CT) and erythrocyte phenotyping (EP). Statistical analysis was performed using linear regression, Spearman correlation test and ROC curve. During the 10 years, 29 practical panels containing 4 ABO and RhD typing (n = 10,382), 2 samples for IAT, IAI and DAT (n = 5,191 respectively), CT (n = 1,611) and EP (n = 1,074) were sent and 21 theoretical evaluations (18,975 questions). The mean number of participants during the study period was 89.5. The growth rate, taking into account the number of services evaluated in 2005 and those in 2015, indicates a growth of 26.6%. Regarding the evaluation of the practical panels, the performance of the indicators evaluated was: ABO>RhD>CT>DAT>IAT>IAI>EP. In the individual evaluation, the performance of the indicators evaluated was: IAI>IAT>EP>CT>ABO>DAT>RhD. RESULTS: Twenty-eight HS patients (71%), three (11%), four (14%) and five (11%) were found to be the worst performers in more than one parameter evaluated (24.13% of the total). The Spearman correlation test identified that the worst practical performance is related to the profile of services that do not perform certain techniques, as well as those that have difficulty answering questionnaires. The general percentage of correctness of the theoretical evaluation does not present a trend of stable results. The individual percentage of correctness of the theoretical evaluation varies from 80% to 99.9%.

Orientador: Elenice Deffune
Resumo: A Coordenação Geral de Sangue e Hemoderivados CGSH, do Ministério da Saúde, comprometida com a missão de elaborar políticas que promovam o acesso da população à atenção hematológica e hemoterápica de forma segura e com qualidade, desenvolve suas ações em consonância com os princípios e as diretrizes do Sistema Único de Saúde – SUS e através da ANVISA implantou em 2001 a Avaliação Externa da Qualidade em Imuno-hematologia (AEQIH) contando com 8 unidades produtoras (UP). Em 2005 o Hemocentro de Botucatu passou a integrar as UP. Este trabalho tem como objetivo avaliar o desempenho dos serviços de hemoterapia (SH) da área de abrangência da Grande São Paulo, sob responsabilidade da UP de Botucatu no período de 2005-2015 levando em consideração diferentes indicadores: número de serviços atendidos/índice de adesão; erros e acertos nas técnicas de tipagem ABO e RhD, pesquisa de anticorpos irregulares (PAI), identificação de anticorpos irregulares (IAI), teste da antiglobulina direta (TAD), prova cruzada (PC) e fenotipagem eritrocitária (FE). A análise estatística realizada foi a de regressão linear, teste de correlação de Spearman e Curva ROC. Durante os 10 anos foram enviados 29 painéis práticos contendo 4 tipagens ABO e RhD (n=10.382), 2 amostras para PAI, IAI e TAD (n=5.191 respectivamente), PC (n=1.611) e FE (n=1.074) e 21 avaliações teóricas (18.975 questões). A média de SH participantes durante o período determinado foi de 89,5. O índice de crescimento, levando em considera... (Resumo completo, clicar acesso eletrônico abaixo)
Mestre

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Dissertacao (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP
FAPESP:99/06803-9

Abstract Point-of-care testing (POCT) is defined as laboratory tests performed outside the traditional clinical laboratory close to the patient at the time and place where care is received, such as hospitals and healthcare centers. The main reason for the use of POCT is that they provide rapid results and enable prompt interventions, with hopefully improved patient outcomes. All phases of laboratory procedure are included in POCT offering many opportunities for errors, which can influence on patients’ treatment. The measurements are more often performed by nurses than by laboratory professionals. These nurses have different kinds of professional backgrounds, e.g. public health nurses, registered and practical nurses, with minimal or no knowledge of laboratory procedures. The aim of the study was to develop a two-step training and management strategy for nurses to do POCT in hospital and primary healthcare center. In accordance with the strategy, with reasonable investment of laboratory resources, designated contact nurses were first trained in POCT by laboratory professionals, after which the contact nurses trained other nurses in POCT their respective units. Blood glucose, the most common point-of-care (POC) test, was chosen as an example to investigate the influence of training on the quality of the test performed by nurses. The quality of blood glucose measurements was studied by analyzing the control results obtained by nurses and biomedical laboratory scientists (BLSs). The study participants included nurses who were either untrained or trained to do POCT by using the developed interactive two-step training strategy. In conclusion, the nurses trained by using interactive two-step strategy achieved near-similar quality of blood glucose measurements as BLSs. The good quality of glucose measurements, once achieved by training, was also sustained in the long-term
Tiivistelmä Määritelmän mukaan vieritutkimuksiksi kutsutaan laboratoriotutkimuksia, joita tehdään perinteisen laboratorion ulkopuolella, tarvittaessa lähellä potilasta sairaalassa ja perusterveydenhuollon alueella. Pääasiassa vieritutkimuksia tehdään silloin kun tulos halutaan saada nopeasti ennen hoitopäätöstä tai tulevaa toimenpidettä. Vieritutkimusten tekeminen sisältää kaikki laboratoriotyön vaiheet ja jokaisessa vaiheessa on mahdollisuus tehdä virheitä, jotka voivat vaikuttaa potilaiden hoitoon. Laboratorioammattilaisten sijaan määrityksiä tekevät yhä useammin hoitajat sairaalan eri yksiköissä ja perusterveydenhuollon alueella. Näillä hoitajilla on erilainen ammatillinen peruskoulutus, kuten perushoitajan tai sairaanhoitajan koulutus, ja heillä on vähän tai ei ollenkaan tietoa laboratoriomenetelmistä. Tämän tutkimuksen tarkoituksena oli kehittää hoitajien vieritutkimustoimintaan koulutus- ja hallintomalli, joka toimisi sekä sairaalassa että terveyskeskuksessa. Strategian perusteena oli käyttää suhteellisen vähän laboratorioresursseja ja päästä silti hyvään laadulliseen lopputulokseen. Strategiaksi valittiin kaksiportainen, vuorovaikutteinen koulutusmalli, jossa laboratorioammattilaiset kouluttivat sairaalan ja perusterveydenhuollon yksiköissä ns. yhdyshenkilöt, jotka puolestaan kouluttivat edelleen oman yksikkönsä muut hoitajat tekemään vieritutkimuksia. Veren glukoosimääritys, joka on yleisin vieritutkimus, valittiin esimerkkitutkimukseksi tutkittaessa koulutuksen vaikutusta hoitajien tekemien vieritutkimusten laatuun. Veren glukoosimääritysten laatutasoa tutkittiin analysoimalla hoitajien ja laboratoriohoitajien tekemien kontrollinäytteiden tuloksia. Tutkimukseen osallistui hoitajia, jotka oli koulutettu kehitetyllä vuorovaikutteisella kaksiportaisella koulutusstrategialla vieritutkimusten tekemiseen, sekä hoitajia, jotka eivät olleet saaneet vastaavaa koulutusta. Koulutusmallin avulla hoitajien suorittamien vieritutkimusten laatu parani ja he saavuttivat lähes saman laatutason kuin laboratoriohoitajat. Hyvä, kerran saavutettu glukoosimääritysten laatutaso säilyi myös pitkällä aikajaksolla

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O emprego de tecnologias gerenciais que buscam a melhoria do desempenho com a satisfação do cidadão na Administração Pública brasileira cresceu, sobretudo a partir do movimento de Reforma Gerencial desencadeado na década de 90. Dentre estas tecnologias destaca-se a Gestão da Qualidade, especialmente, os Sistemas de Gestão da Qualidade ISO 9001:2008. Com base em modelos lógicos causais, operacionais e teóricos, este estudo avaliou a implantação do Programa de Gestão da Qualidade IS0 9001:2008 na Coordenação Geral de Sangue e Hemoderivados, do Ministério da Saúde (CGSH/MS), identificando as motivações para implantação, o grau de implantação, os fatores que favoreceram e dificultaram e os efeitos decorrentes, percebidos até o momento. Constatou-se que o Sistema de Gestão da Qualidade (SGQ) encontra-se parcialmente implantado. Em termos de seus componentes, é completa a implantação dos documentos e procedimentos, e são parciais as implantações da capacitação da força de trabalho, do mapeamento e da padronização dos processos, da adequação aos requisitos da ISO 9001, das auditorias internas. Quanto ao componente da certificação externa, a implantação ainda é incipiente. Os motivos que levaram à implantação foram de caráter interno, relacionados à organização e à melhoria do desempenho. A certificação externa foi considerada motivo secundário. O elemento de maior destaque nos fatores que favoreceram a implantação foi a liderança desempenhada pelo Coordenador Geral, seguida e reproduzida pelos responsáveis de áreas junto à suas respectivas equipes de trabalho. As dificuldades identificadas foram relacionadas a aspectos operacionais como limitações de entendimento da norma, falta de sistema de informática e capacitação deficiente. Como efeitos, foram identificadas as melhorias da organização e da rotina com reflexos nos resultados organizacionais. O acréscimo de trabalho sentido pelos técnicos foi considerado um efeito negativo do programa, o que pode vir a ser uma ameaça à sua continuidade.

Magister Pharmaceuticae - Mpharm
The aim of this study was to determine quality control specifications needed for a dossier and an investigator's brochure of A. afra capsules, which can be used to motivate the registration and clinical testing of A. afra capsules in chronic asthma. The specific objectives were: (1) to establish the minimum product quality requirements for registration of A. afra capsules, (2) to prepare and pharmaceutically characterize a capsule product of A. afra freeze dried aqueous extract (FDAE) suitable for registration, and (3) to identify pharmaceutical product quality aspects of an investigator's brochure (IB) that would be appropriate for use in motivating a clinical trial of A. afra capsules in chronic asthma.

Thesis (MScAgric)--Stellenbosch University, 2013.
ENGLISH ABSTRACT: The WineScan FT120 is widely used in wine laboratories across South Africa. The WineScan FT120 uses Fourier transform infrared (FT-IR) spectroscopy with multivariate data analysis to correlate spectra with chemical compositional data. Ready-to-use, commercially available calibration models for a FT-IR spectroscopy instrument are an advantage for unskilled users and routine analysis. Introducing spirit products to this technology introduced new interferences, which necessitated vastly different calibrations models to compensate for the changes. Accuracy, precision and ruggedness of the reference methods validated during method validation, verified the suitability of the reference methods used to quantify the parameters in question before calibration model building was attempted. Various principal component analysis (PCA) were performed prior to the calibration step with the aim to identify outliers and inspect groupings. PCA models could identify samples with atypical spectra and differentiate between product types. Two tactics regarding data sets for calibration set-up was experimented with, all the products together and calibration models per product. Partial least squares (PLS) regression was used to establish the calibration models for ethanol, density, obscuration and colour. With all the calibration models, the calibration models based on the product specific data sets, achieved better predicting statistics. The best performing ethanol calibration models achieved Residual mean square error of prediction (RMSEP) = 0.038 to 0.106 %v/v and showed significant improvement on previously reported prediction errors by Lachenmeier (2007). The results for the density calibration showed a similar trend, with the product specific calibration models outperforming the calibration model when all samples were included into one calibration model. This study produced novel results for quantification of obscuration (RMSEP = 0.10 and 0.09 in blended brandies and potstill brandies, respectively) and colour (RMSEP < 2.286 gold units) of brandies and whiskies. The correlation coefficients (R²) between true and predicted values, for the four parameters tested, indicated good to excellent precision (0.8 < R² < 1.0). Minimising the variation between the samples of the data set, gave more accurate regression statistics, but this resulted in a lower residual predictive deviation (RPD) value (< 5) that indicated models were not suitable for quantification. Adding more samples per product will add more variability into a data set per product, increase the SD and result in an increase in the RPD. The results pave the way for the development of calibration models for the quantification of other parameters for specific products. Following the groupings of product types, further classifications of brandy brands were investigated. PCA plots showed clear separation between potstill brandies and blended brandies and some degree of clustering between some of the blended brands was observed. Classification of brandies were investigated using the Soft Independent Modeling of Class Analogy (SIMCA) approach resulting in a total correct classification rates between 81.25% and 100% for the various brandy brands. These preliminary results were very promising and highlight the potential of using FT-IR spectroscopy and multivariate classification techniques as a tool for rapid quality control and authentication of brandy brands. Using this work as base for further classification projects, this could be of great benefit to the alcoholic beverage industry of South Africa. Future work will involve the development of a database comprised of more products guaranteed authentic to expand the discriminating options. The results suggest FT-IR spectroscopy could be useful in authentication studies.
AFRIKAANSE OPSOMMING: Die WineScan FT120 is ‘n algemeen gebruikte instrument regoor Suid-Afrika. Die WineScan FT120 gebruik Fourier-transformasie-infrarooi (FT-IR) spektroskopie tesame met multiveranderlike statistiese metodes om spektra te korreleer met chemiese samestellingsdata. Die kommersieël beskikbare kalibrasiemodelle vir die FT-IR spektroskopie-instrument is ‘n voordeel vir onbedrewe gebruikers en roetine ontleding. Blootstelling van spiritusprodukte aan die tegnologie, het nuwe hindernisse bekend gestel en dus is verskillende kalibrasiemodelle genoodsaak om hiervoor te kompenseer. Akkuraatheid, presiesheid en ruheid van die verwysingsmetodes is geëvalueer tydens metodevalidasie. Die verwysingsmetodes is geskik verklaar vir die konstruksie van die kalibrasiemodel met geverifieërde akkurate verwysingsresultate. Verskeie multiveranderlike hoofkomponentanalise (MVK) was uitgevoer voor die kalibrasiestap met die doel om uitskieters te identifiseer en groeperings te inspekteer. MVK modelle kon monsters met atipiese spektra identifiseer en onderskei tussen verskillende produk tipes. Twee taktieke aangaande datastelsamestelling is getoets tydens kalibrasiemodel-opstelling, al die produkte saam en kalibrasiemodelle per produk soos met die MVK aangedui. Parsiële kleinste kwadraat (PKK)- regressie is gebruik vir die opstel van die kalibrasiemodelle vir etanol, digtheid, obskurasie en kleur. Met al die kalibrasiemodelle het die produk spesifieke kalibrasiemodelle beter regressiestatistiek gelewer. Die beste presterende etanol kalibrasiemodelle het ‘n standaardvoorspellingsfout (SVF) = 0.038 tot 0.106 %v/v bereik en het ‘n beduidende verbetering getoon op vorige gerapporteerde studies op spiritusprodukte (Lachenmeier, 2007). Die resultate vir die digtheidskalibrasiemodelle het ‘n eenderse tendens getoon soos die etanol, met die produk spesifieke kalibrasiemodelle wat beter presteer het. Hierdie studie was eerste in sy soort met die kalibrasiemodel vir obskurasie (SVF = 0.10 en 0.09 in gemengde brandewyne en potketel brandewyne, onderskeidelik) en kleur (SVF < 2.286 goud eenhede) van brandewyne en whiskies. Die bepalingskoëffisiënt (R²) vir die vier parameters, dui op goeie tot uitstekende presiesheid (0.8 < R² < 1.0). Vermindering van die variasie tussen die monsters in die datastel, het meer akkurate regressiestatistiek teweeg gebring, maar ‘n laer relatiewe voorspellingsafwyking (RVA) waarde (<5) tot gevolg gehad wat aan dui dat hierdie modelle nie geskik is vir sifting of kwantifisering nie. Die byvoeging van meer monsters per produk sal meer verskeidenheid in die datastel per produk bring, wat dan die standaardafwyking sal laat toeneem en uiteindelik die RVA laat toeneem. Die resultate het die fondasie gelê vir die ontwikkeling van kalibrasiemodelle vir die kwantifisering van ander parameters vir spesifieke produkte. As opvolg tot die groeperings van die produk tipe, waargeneem in die MVK modelle, was klassifikasie van brandewyn handelsmerke ondersoek. MVK modelle het duidelike skeiding gewys tussen potketel en gemengde brandewyne en tot ‘n sekere mate groepering tussen handelsmerke. Klassifikasie van brandewyne was ondersoek met behulp van the Soft Independent Modeling of Class Analogy (SIMCA) met die resultaat van ‘n totale korrekte klassifikasiekoers van tussen 81.25% en 100% vir die verskeie brandewyn handelsmerke. Hierdie voorlopige resultate toon belowend en beklemtoon die potensiaal van FT-IR spektroskopie en chemometrics tegnieke as toerusting vir die vinnige kwaliteitskontrole en egtheid van brandewyn handelsmerke studies. Met hierdie werk as basis vir verdere klassifikasie projekte, kan dit ‘n groot aanwins wees tot die alkoholiese drank industrie van Suid-Afrika. Toekomstige werk sal insluit die ontwikkeling van ‘n databasis saamgestel met meer gewaarborgde egte produkte om die klassifikasie uit te brei.

Platelets are the smallest cells in the blood. They are formed in the bone-marrow and are important for the blood coagulation. Platelet tranfusions are given to patients propyhlactically before an operation but also in therapeutical purpose in connection with bleeding. It’s importent that the quality controls of the platelet concentrates are reliable.

ADVIA®60 (Bayer HealthCare) is a fully automated cell counter which uses impedance principle to count platelets in blood samples. The purpose of the study was to evaluate this new instrument for use in the blood bank of Akademiska Sjukhuset in Uppsala. The instrument was bought to be used for quality control of platelet concentrates. 30 samples from platelet concentrates, from both apheresis and from buffy coats, were analyzed 10 times each on ADVIA®60 and the coefficient of variation (CV) was calculated for each sample. CV variated from 0,8 % to 2,9 % which is good considering that according to Bayer HealthCare the CV should be < 5 % for thrombocytes on ADVIA®60. The instrument was newly calibrated when the study was performed. Platelet count can also be performed by immunological or optical principles.

Thesis (M. Tech.) - Central University of Technology, Free State, 2006
A multi-threaded, multi-agent image recognition software application called RecMaster has been developed specifically for the purpose of quality control in a production environment. This entails using the system as a monitor to identify invalid objects moving on a conveyor belt and to pass on the relevant information to an attached device, such as a robotic arm, which will remove the invalid object. The main purpose of developing this system was to prove that a desktop computer could run an image recognition system efficiently, without the need for high-end, high-cost, specialised computer hardware. The programme operates by assigning each agent a task in the recognition process and then waiting for resources to become available. Tasks related to edge detection, colour inversion, image binarisation and perimeter determination were assigned to individual agents. Each agent is loaded onto its own processing thread, with some of the agents delegating their subtasks to other processing threads. This enables the application to utilise the available system resources more efficiently. The application is very limited in its scope, as it requires a uniform image background as well as little to no variance in camera zoom levels and object to lens distance. This study focused solely on the development of the application software, and not on the setting up of the actual imaging hardware. The imaging device, on which the system was tested, was a web cam capable of a 640 x 480 resolution. As such, all image capture and processing was done on images with a horizontal resolution of 640 pixels and a vertical resolution of 480 pixels, so as not to distort image quality. The application locates objects on an image feed - which can be in the format of a still image, a video file or a camera feed - and compares these objects to a model of the object that was created previously. The coordinates of the object are calculated and translated into coordinates on the conveyor system. These coordinates are then passed on to an external recipient, such as a robotic arm, via a serial link. The system has been applied to the model of a DVD, and tested against a variety of similar and dissimilar objects to determine its accuracy. The tests were run on both an AMD- and Intel-based desktop computer system, with the results indicating that both systems are capable of efficiently running the application. On average, the AMD-based system tended to be 81% faster at matching objects in still images, and 100% faster at matching objects in moving images. The system made matches within an average time frame of 250 ms, making the process fast enough to be used on an actual conveyor system. On still images, the results showed an 87% success rate for the AMD-based system, and 73% for Intel. For moving images, however, both systems showed a 100% success rate.

Segundo a legislação brasileira e normas internacionais, os concentrados de hemácias (CH) devem ser mantidos sob controle rigoroso de temperatura, armazenados de 2 a 6°C e transportados de 1 a 10°C, por até 24 horas. Entretanto, não existem evidências científicas de que estes valores sejam relevantes para manutenção de qualidade, segurança e viabilidade dos CH. O objetivo deste trabalho foi monitorar parâmetros laboratoriais in vitro em dois tipos de CH (CPDA-1, preparado pela metodologia do plasma rico em plaquetas e em SAGM preparado pelo buffy-coat), no decorrer de condições normais de armazenamento e em temperaturas de transporte inadequadas. O trabalho foi executado em três etapas. Na primeira etapa, foram estabelecidos os valores de referência para os dois tipos de CH armazenados em condições normais, através de testes laboratoriais semanais para determinação de hematócrito, hemoglobina total, hemoglobina plasmática, grau de hemólise, glicose, lactato, desidrogenase lática e potássio. Na segunda etapa, amostras de CH foram submetidas a temperaturas entre -2°C e +1°C, ou entre 11 e 15°C, por um período de 6 horas ou 24 horas, no 14º dia de armazenamento. Na terceira etapa os CH foram expostos a condições de estresse extremo, submetendo-os a temperaturas entre -2°C e +1°C ou entre 22°C e 25°C, por período de 48 horas. Os resultados dos testes laboratoriais das segunda e terceira etapas foram comparados com controles e aos valores de referência da primeira etapa. Nas unidades de CH em CPDA-1 foram encontrados valores significativamente mais elevados de potássio, hemoglobina livre, grau de hemólise, lactato e LDH do que nos CH em SAGM, enquanto que a concentração de glicose foi muito mais baixa em CH-CPDA1. Na 2ª etapa, exposições por até 24 horas em temperaturas de até - 2°C ou até 15°C não causaram diferenças significativas nas dosagens de hemoglobina livre, grau de hemólise, glicose, lactato, LDH e potássio quando comparados aos controles. Amostras de CH-CPDA1, quando avaliadas imediatamente após período de 48 horas de exposição, apresentaram resultados de glicose superiores aos controles quando submetidas a -2°C e inferiores ao controle quando a 25°C. Exposições por até 48 horas em temperaturas de até -2°C ou até 25°C não causaram diferenças significativas na hemoglobina livre, grau de hemólise, lactato, LDH e potássio quando comparados aos controles, nos dois tipos de CH. Nesse trabalho foram elaborados perfis padrão de parâmetros laboratoriais para dois tipos de CH. Estes perfis padrão constituirão uma ferramenta de grande utilidade para controle de qualidade e monitoramento das lesões de armazenamento em bolsas de CH produzidas na Fundação HEMOMINAS. Nossos resultados demonstraram que bolsas dos dois tipos de CH submetidas a temperaturas de - 2°C ou 14°C por períodos inferiores a 24 horas não apresentam alterações significativas nos parâmetros laboratoriais avaliados in vitro e permitiram algumas elaboramos recomendações práticas e importantes para serviços de hemoterapia. Entretanto, ainda não existem ainda evidências suficientes na literatura para modificação das normas de temperatura e tempo de transporte atualmente preconizadas pela legislação nacional e internacional.
The Brazilian legislation and international guidelines require that red blood cell concentrates (RBC) are kept under a strict temperature control, stored between 2 and 6°C and transported between 1 and 10°C for up to 24 hours. Nevertheless, there is no scientific evidence that these values are relevant to maintain RBC quality, safety and viability. This study was performed in order to monitor in vitro laboratorial variables of two different RBC types (CPDA-1, prepared using the platelet-rich plasma methodology, or SAGM, prepared using the buffy-coat) stored under normal conditions or under inadequate temperatures during transportation. The study had three phases. In the first phase, weekly laboratorial tests were performed to establish the reference values of hematocrit, total hemoglobin, plasma hemoglobin, rate of hemolysis, glucose, lactate, lactic acid dehydrogenase (LDH) and potassium, for each of the RBC types stored under normal conditions. In the second phase, RBC samples were submitted to temperatures between -2°C and +1°C, or between 11 and 15°C, for 6 hours or 24 hours, on the 14th storage day. Laboratorial test results were compared to a control group (2-6°C) and to the reference values established in the 1st phase. In the third phase, RBCs were exposed to extreme stress, i.e., temperatures between -2°C and +1°C or between 22°C and 25°C, for 48 hours, and the laboratory test results were compared to a control group. CPDA1-RBC had higher levels of potassium, free hemoglobin, rate of hemolysis, lactate and LDH compared to SAGM-RBC, whereas glucose was significantly lower in CPDA1. In the second phase, exposure for up to 24 hours in temperatures until -2°C or 15°C had no effect on free hemoglobin, rate of hemolysis, glucose, lactate, LDH and potassium when compared to control. CPDA1 samples right after the 48-h exposure had higher glucose levels than controls when kept at -2°C and lower than control if exposed to 25°C. Exposures up to -2°C or 25°C for up to 48 hours had no effect on free hemoglobin, rate of hemolysis, lactate, LDH and potassium when compared to control groups, both for CPDA1-RBC and SAGM-RBC. In this study, it was established standards for laboratory analyses for two different RBC types. Such standards will comprise valuable and useful tools for the quality control and monitoring of storage lesions of RBC units produced by Fundação HEMOMINAS. Our results demonstrate that units from both RBC types submitted to -2°C or 14°C for up to 24 hours had no significant changes in in vitro laboratory variables and allow some practical and important recommendations for hemotherapy services. Nevertheless, there are not enough evidences in the literature to support changes in the current guidelines for transportation recommended by national and international legislation.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Tese (Doutoramento)
IPEN/T
Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP
FAPESP:06/54851-8

Orientadores: Vivaldo Silveira Junior, Vania Regina Nicoletti Telis
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos
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Doutorado
Engenharia de Alimentos
Doutor em Engenharia de Alimentos

CAPES
Os Sistemas Produto-Serviço (PSS) têm como finalidade satisfazer as necessidades dos clientes por meio de um serviço que integra produtos, redes de apoio e infraestrutura. Embora o PSS seja estudado por autores em nível mundial, existem muito poucos métodos para o projeto de PSS a partir da qualidade percebida pelo cliente. O propósito do presente trabalho é sugerir uma ferramenta que incorpore a voz do cliente nas etapas iniciais do desenvolvimento de Sistemas Produto-Serviço, visando criar um modelo de referência e propor as oportunidades de pesquisa futuras. Para atender o objetivo geral, é apresentada a fundamentação teórica baseada numa recompilação da literatura, passando pela definição de PSS, os diferentes tipos de PSS, as vantagens e barreiras na sua aplicação, diferentes modelos para o projeto de PSS e as ferramentas de apoio que incorporam a voz do cliente no Processo de Desenvolvimento de Produtos (PDP) e que, possivelmente, poderiam auxiliar o processo de projeto de PSS. A ferramenta que melhor abordou os requisitos do projeto de PSS é o desdobramento da função qualidade (QFD). O QFD é uma ferramenta efetiva para traduzir a voz do cliente em parâmetros de engenharia, capaz de introduzir o tema da qualidade no desenvolvimento de PSS. A proposta da presente dissertação parte dos trabalhos existentes da aplicação de QFD no projeto de PSS; são melhorados os trabalhos até agora desenvolvidos e exemplificadas por meio da aplicação do modelo numa lavanderia. O modelo para apoiar o desenvolvimento de PSS tem duas barreiras principais, que estão associadas com a avaliação qualitativa da matriz de relacionamento e com a possível complexidade em trabalhar grandes quantidades de requisitos e características de qualidade.
Product-Service Systems (PSS) are designed to satisfy customers’ needs through a service that includes: products, support networks and infrastructure. Although many authors around the world have studied PSS, there are very few methods for service design based on the customers’ quality perception. The purpose of this work is to provide a tool that incorporates the customers’ voice at the early stages of the development of Product-Service Systems and, with this, to provide a reference model and propose future research opportunities. To meet the main objective, literature review was conducted, including the definition of PSS, the different types of PSS, the benefits and barriers of its implementation, different models for designing PSS and the support tools that incorporate the customer´s voice in the Product Development Process (PDP) and that could possibly assist the designing process of PSS. The tool that best addressed the requirements of the PSS design was the Quality Function Deployment (QFD). QFD is an effective tool for translating the customers’ voice into engineering parameters, as it is able to introduce the quality topic into the development of PSS. The starting point of the present work was to improve existing studies of QFD utilization in PSS development. Then the model is application is illustrated with a laundry business case. The model that supports PSS development has two main barriers, which are associated with the relationship matrix qualitative evaluation and with the possible complexity in working with large amounts of quality characteristics.