Qualification Steps Research Articles

CD138 as a Specific CSF Biomarker of Multiple Sclerosis.

The aim of this study was to identify novel biomarkers for multiple sclerosis (MS) diagnosis and prognosis, addressing the critical need for specific and prognostically valuable markers in the field. We conducted an extensive proteomic investigation, combining analysis of (1) CSF proteome from symptomatic controls, fast and slow converters after clinically isolated syndromes, and patients with relapsing-remitting MS (n = 10 per group) using label-free quantitative proteomics and (2) oligodendrocyte secretome changes under proinflammatory or proapoptotic conditions using stable isotope labeling by amino acids in cell culture. Proteins exhibiting differential abundance in both proteomic analyses were combined with other putative MS biomarkers, yielding a comprehensive list of 87 proteins that underwent quantification through parallel reaction monitoring (PRM) in a novel cohort, comprising symptomatic controls, inflammatory neurologic disease controls, and patients with MS at various disease stages (n = 10 per group). The 11 proteins that passed this qualification step were subjected to a new PRM assay within an expanded cohort comprising 158 patients with either MS at different disease stages or other inflammatory or noninflammatory neurologic disease controls. This study unveiled a promising biomarker signature for MS, including previously established candidates, such as chitinase 3-like protein 1, chitinase 3-like protein 2, chitotriosidase, immunoglobulin kappa chain region C, neutrophil gelatinase-associated lipocalin, and CD27. In addition, we identified novel markers, namely cat eye syndrome critical region protein 1 (adenosine deaminase 2, a therapeutic target in multiple sclerosis) and syndecan-1, a proteoglycan, also known as plasma cell surface marker CD138 and acting as chitinase 3-like protein 1 receptor implicated in inflammation and cancer signaling. CD138 exhibited good diagnostic accuracy in distinguishing MS from inflammatory neurologic disorders (area under the curve [AUC] = 0.85, CI 0.75-0.95). CD138 immunostaining was also observed in the brains of patients with MS and cultured oligodendrocyte precursor cells but was absent in astrocytes. These findings identify CD138 as a specific CSF biomarker for MS and suggest the selective activation of the chitinase 3-like protein 1/CD138 pathway within the oligodendrocyte lineage in MS. They offer promising prospects for improving MS diagnosis and prognosis by providing much-needed specificity and clinical utility. This study provides Class II evidence that CD138 distinguishes multiple sclerosis from other inflammatory neurologic disorders with an AUC of 0.85 (95% CI 0.75-0.95).

Product–machine qualification using a process flexibility strategy considering capacity loss

Due to uncertainties in future demands regarding product variety, manufacturers must maintain a balance between capacity investment costs and future demand satisfaction levels, which makes capacity management challenging for a high-value asset industry. Product–machine qualification, which is an essential process in configuring machines to produce new products, plays an important role in allocating appropriate capacity to different products. Motivated by the challenges presented by this real-world trade-off problem, this article develops effective “product–machine” production structures by introducing new process flexibility strategies. The product–machine qualification process is complex and very time-consuming, which generally causes processing machines to experience massive capacity loss. The more flexible a machine is, the more product–machine qualification steps are required and the more capacity will be lost. Traditional process flexibility strategies, such as the long chain strategy, cannot be used directly for product–machine qualification decisions because they all assume that the capacities of machines are constant and that only product demands vary. This article promotes the traditional process flexibility theory by introducing capacity loss into the model. The proposed strategies for balancing process flexibility and capacity loss have proven effective in satisfying uncertain demands by cost-effective capacity-demand matching structures.

Using video-elicitation focus group interviews to explore pre-service science teachers’ views and reasoning on artificial intelligence

ABSTRACT Using video-elicitation focus group interviews, this study aims to reveal pre-service science teachers’ perspectives and reasoning on artificial intelligence as a socioscientific issues-based scenario. Hence, it illustrates the ways the video data were used in the focus group elicitation interviews to understand their interpretations of how their beliefs align with a hypothetical future scenario around artificial intelligence. To demonstrate the phenomenon in depth, a case study design was used. The participants of the study involved 45 third and fourth-year undergraduate students enrolled in a science teacher education programme. For this study, the researcher conducted six open-ended, unstructured video-elicitation focus group interviews. The data was analysed using Dey’s (1993. Qualitative data analysis: A user-friendly guide for social scientists. Routledge) qualitative analysis steps of description, qualification, and association. The findings indicated that the participants’ views and reasoning vary in the context of artificial intelligence technologies. The fictional scenario depicted in the video-elicitation interviews both helped and challenged them to share their perspectives on the issue. Moreover, several aspects of SSI were thoroughly discussed during the interviews.

Design and Qualification of an Additively Manufactured Manifold for Aircraft Landing Gears Applications

The continuous pursuit of reducing weight and optimizing manufacturing processes is increasingly demanded in transportation vehicles, particularly in the aerospace field. In this context, additive manufacturing (AM) represents a well-known technique suitable for re-engineering traditional systems, minimizing the product’s weight/volume and print time. The present research activity allowed for the exploration of the feasibility to replicate a conventional hydraulic manifold already certified for defence application with a lightweight and more compact issue through typical stringent aeronautical qualification steps. Computational modelling with lab test efforts made it possible to assess the compliance of the device with airworthiness certification requirements, giving a special focus to the fulfilment of structural requirements. In particular, the fatigue life characterization is still a crucial point to be well investigated in aeronautical components dfAM (designed for additive manufacturing) to demonstrate the maturity of the technology in the certification scenario. The new AM-driven design offers a more than 40 per cent weight reduction.

Development and Basic Qualification Steps towards an Electrochemically Based H-Sensor for Lithium System Applications

IFMIF-DONES, or the InternationalFusionMaterialsIrradiationFacility-DEMOOrientedNeutronSource, is a facility for investigations into foreseen fusion power plant materials using the relevant neutron irradiation of 14 MeV. This special n-irradiation is generated by the interaction of deuteron beams with liquid lithium. A critical issue during the operation of IFMIF-DONES is the enrichment of dissolved impurities in the Li-melt loops. The danger occurs as a result of hydrogen-induced corrosivity and embrittlement of the loop components, as well as the security hazards associated with the radioactive tritium. Hence, the application of liquid lithium in IFMIF-DONES requires a suitable impurity control system for reliable and low-level maintenance under the operating conditions of DONES. Regarding those requirements, an electrochemical sensor for hydrogen monitoring was developed in the frame of an international EUROFusion–WPENS task, to determine H-concentrations via the electro-motive force (EMF) of Li-melts and a suitable online-monitoring system. Long-term tests demonstrated that the sensor fulfills the requirements of chemical and mechanical stability and functionality under the harsh Li environment under the planned DONES conditions. Obtained results and operational experiences will be discussed in regard to application windows, reproducibility and calibration needs. Additionally, recommendations will be outlined for upgraded systems and future qualification needs.

O-228 How to introduce time-lapse technology in the IVF lab

Abstract Although there is conflicting evidence on the actual clinical relevance of time-lapse technique (TLT) it is an add on technique that does come along with several advantages that would justify its use. However, once the decison has been made to go with TLT it has to be brought to mind that the European Tissues and Cells Directive dictates that new equipment is qualified accordingly before used routinely. This process is usually done according to GMP standards, e.g. a proper design qualification (DQ) would identify the most superior equipment which then undergoes further qualification steps such as installation (IQ), operational (OQ) and performance qualifications (PQ). The latter should involve a comparison with generally accepted laboratory KPIs, a process which would allow to establish levels of competence and aspirational benchmark. Upon proper qualification and clearance TLT can be an important tool in an existing quality management system, e.g. for evaluation of inter- and intraobserver variation, implementation of new consumables, and for testing the safety and efficacy of new lab methods.

E-ZAKAT: AN APPROACH FOR ZAKAT MANAGEMENT TO ERADICATE POVERTY

This paper has shown an online-based zakat management system named E-ZAKAT. Zakat is one of the main foundational goals of the world’s second-largest religion, Islam. So, it has indisputable importance for a country as well as the world economy and poverty eradication. During the COVID-19 pandemic, people have become habituated with the online system due to unavoidable situations, such as education and commodity market has now turned into online systems. However, an online base zakat management system for both donors and seekers has not prevailed widely. Here in this proposed system, the donor can calculate, donate their zakat, and the seeker can apply to receive it. Instead of providing cash, business or agricultural help is planned to ensure the economic stability of a low-income family. For this purpose, the expectant can claim support for green farming, agricultural equipment, or money to start a small business after ensuring the required verification and qualification steps. The proposed dynamic web application E-ZAKAT will provide an easier and hassle-free system for zakat donors and seekers with an attractive design. As a result, proper utilization of our system could provide a positive impact to change our society as well as our world.

A Review on qualification of the tablet compression machine

Validation is the art of designing andpracticing the designed steps alongside with the documentation. Validation is one of themostimportant steps in maintaining &achievingthe quality of the final product group after batch. The qualification of the equipment and systems are planning to carry out the tests and record the tests. We cannot be manufacturing the product, without an equipment. If the equipment is validated, we can ensure that our product is of the top-quality. Validation of the equipment is known as Qualification. To making different kinds of dosage forms, various equipment’s are used. Here, this article concentrates on the equipment qualification for theTablet compression machine. It gives in detail, qualification steps of the equipment, which is used for the manufacturing process through wet granulation. Qualification, an ideal step for equipment validation, is the action undertaken to demonstrate the intended use and performance of the utilities and equipment.The individual steps of qualification such as design, installation, operational and performance qualification, were done in order to qualify the equipment. Blueprint of equipment validation was also included and the tablets were tested for physical parameters such asappearance, punch Shape, punch diameter, upper punch, lower punch, hardness, weight variation, friability, and thickness.

Quantification of biomarkers for beef meat qualities using a combination of Parallel Reaction Monitoring- and antibody-based proteomics

We and others have identified biomarker candidates of tenderness or marbling, two major attributes of bovine meat-eating qualities for consumers’ satisfaction. In this study, Reverse Phase Protein Arrays (RPPA) and targeted mass spectrometry assays using Parallel Reaction Monitoring (PRM) were developed to test whether 10 proteins pass the sequential qualification and verification steps of the challenging biomarker discovery pipeline. At least MYH1, TPI1, ALDH1A1 and CRYAB were qualified by RPPA or PRM as being differentially abundant according to marbling values of longissimus thoracis and semimembranosus muscles. Significant mathematical relationships between the individual abundance of each of the four proteins and marbling values were verified by linear or logistic regressions. Four proteins, TNNT1, MDH1, PRDX6 and ENO3 were qualified and verified for tenderness, and the abundance of MDH1 explained 49% of the tenderness variability. The present PRM and RPPA results pave the way for development of useful meat industrial multiplex-proteins assays.

Non-destructive techniques for evaluating the reliability of high frequency active devices

SiGe and GaN technologies have achieved rapid development over the last two decades. High level of RF circuit integration on Si low cost substrates open the way for large development of SiGe HBTs, while needs for high power density make GaN HEMT a key technology for solid state power modules. As both of these technologies achieve very elevated frequencies, they become strong contenders to GaAs technologies. Then reliability studies are needed to improve the process at the lower technology readiness level scale, and to stabilize the technological process till the final qualification step. To make an efficient diagnostic on the causal origin of the physical root mechanisms involved during the application of a stress, a multi-tool approach is mandatory to secure the diagnostic. In this paper, case studies on SiGe HBT and GaN HEMT stressed devices are proposed through the cross-analysis of low frequency noise spectral densities, of electrical transient measurements, and of TCAD simulations.

The development of a standard qualification protocol for all climatic and thermostatic chambers according to the requirements of the Good Manufacturing Practices (GMP) and the standards of characterization: NF X 15-140 and NF EN 60068-3.

The qualification of climatic and thermostatic chambers is not based on a single standard, but it also requires the control of several standards such as NF X 15-140, NF EN 60068-3 and the requirements of the Good Manufacturing Practices (GMP). So, currently the qualifiers only take into account the standard NF X 15-140 or NF EN 60068-3 to make their qualification, without giving importance to other criteria that must be treated or accurately tested and that are not mentioned in these standards, but they are cited in other references such as GMP (Good Manufacturing Practices). Because with the standards NF X 15-140 or NF EN 60068-3 we can only judge on the conformity of the distribution of temperature and humidity into the chamber. That is to say, in qualification terms, it is the last step of the qualification, which is the PQ (Performance Qualification). While in the GMP, we find the other steps of qualification, which are the IQ (Installation Qualification) and the OQ (Operational Qualification) and even in the GMP, they are not well detailed. Thanks to the use of the characterization standards such as NF X 15-140 and NF EN 60068-3 and the requirements of the Good Manufacturing Practices, we have been able to develop a standard qualification protocol. Indeed, this protocol could be used for all climatic and thermostatic chambers for the purpose of their qualification. Also, it could allow us to make a judgment on the conformity or not of the chamber to qualify

The Qualification of the Additively Manufactured Parts in the Aviation Industry

The aviation is a highly engineered industry. It has precise manufacturing requirements. Because of these requirements, the aviation has been forced to be a pioneer for implementation of novel manufacturing techniques such as Computer Aided Design (CAD), Computer Aided Manufacturing (CAM) and newly-developed materials such as carbon fiber composites. These technologies and materials were firstly adopted by the aviation industry. Many processes and materials were used by other sectors such as automotive, ship construction and white goods etc. after the aviation industry used those as regular ones. On the other hand, the aviation industry is a booming sector because it is leveraged by increasing passenger traffic. Passenger traffic projections show that the aviation industry will continuously expand. Naturally, this expansion will attract many companies into the aviation industry and therefore attraction will conclude a fiercer competition environment in the aviation industry. At the conclusion, the companies in the aviation industry will look for implementation of novel technologies since they will not want to fall behind their competitors. On the other hand, the airworthiness authorities always keep their <i>decision and regulation maker position</i> while the companies are the followers. It can be put forward that the most difficult side of the implementation of novel technologies into aviation industry is to get along with the strict rules and regulations which are put by international and national airworthiness authorities. In this context, the question of <i>how to qualify the additively manufactured parts (AMPs)</i> is waiting for the answer. The additive manufacturing (AM) is a strong process which has been implemented into aviation industry rapidly while the qualification and certification processes still have many challenges. This paper provides the pathway and the steps of qualification for additively manufactured parts (AMPs) besides the categorization of AM technologies and the impact of weight reduction over flight operation cost.

Method Transfer and Full Method Validation, Partial Validation in cGMP Environment

This paper describes the current method transfer and method validation process following FDA guidance and ICH guidelines in a cGMP environment. The analytical method validation and transfer have been playing a key role in Phase 1 to Phase 3 projects. This paper discusses the method validation and method transfer based on the phase of relevance in the GMP environment. It also describes the number of validation or qualification steps required for the method transfer. When the analytical methods are utilized to generate results about the characteristics of drug-related samples it is essential that the results are trustworthy. They may be utilized as the basis for decisions relating to administering the drug to patients. Analytical method validation required during drug development and manufacturing and these analytical methods is fit for their intended purpose. To comply with the requirements of GMP pharmaceutical industries should have an overall validation policy that documents how validation will be performed. The purpose of this validation is to show that processes involved in the development and manufacture of the drug, production, and analytical testing can be performed in an effective and reproducible manner. This review article provides guidance on how to perform validation characteristics for the analytical method which are utilized in pharmaceutical analysis.

Key Discovery and Prospect Qualification Steps

The Major Gifts ReportVolume 21, Issue 1 p. 5-5 Making One-on-One Calls Key Discovery and Prospect Qualification Steps First published: 07 December 2018 https://doi.org/10.1002/mgr.31122Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume21, Issue1January 2019Pages 5-5 RelatedInformation

Qualification of ITER PF6 helium inlet

The Poloidal Field (PF) coils are one of the main sub-systems of the ITER magnets. The PF6 coil is being manufactured by the Institute of Plasma Physics, Chinese Academy of Sciences (ASIPP) as per the Poloidal Field coils cooperation agreement signed between ASIPP and Fusion for Energy (F4E). As one of the critical components, helium inlet locates on the innermost turn and supplies the coil with supercritical helium. During Tokamak operation, the helium inlet will undergo huge cyclic electromagnetic loads and thermal cycling during cooling down and warming up.This paper focus on the main steps of ITER PF6 helium inlet qualification. Helium inlet hole drilling and stainless steel wrapping removal were firstly been carried out. Helium inlet welding with full penetration by automatic welding machine was then performed, followed by leak proof test, non-destructive test, fatigue test and tomography test. At the end, the samples were sectioned for micro and macro inspection. The results show ITER PF6 helium inlet qualification has successfully met the requirements of PF procurement agreement(PA) and was approved by ITER IO.

Optimization of filament winding parameters for the design of a composite pipe

Abstract In the oil&gas field, common steel pipelines experience well-known problems of corrosion and maintenance. The design with composite materials could avoid these problems and provide lightness to the overall structures. Standards and regulations guide the designer through the qualification steps, but they are constantly under review based on the increasing knowledge of the long term mechanical behaviour of these materials. The aim of this work is to provide the designer with an analytical tool for the optimal design of a composite plain pipe, i.e. minimizing the wall thickness. The paper presents considerations useful in the design stage for the selection of the optimal fiber, matrix, volume fraction V f , and winding angle θ. The study simulates tests with inner pressure and axial loads, in accordance with the main applicable standards. Based on the analytical estimations, we found a locus of optimal technological parameters with volume fraction 40% V f

JOKARUS - design of a compact optical iodine frequency reference for a sounding rocket mission

We present the design of a compact absolute optical frequency reference for space applications based on hyperfine transitions in molecular iodine with a targeted fractional frequency instability of better than 3 × 10−14 after 1 s. It is based on a micro-integrated extended cavity diode laser with integrated optical amplifier, fiber pigtailed second harmonic generation wave-guide modules, and a quasi-monolithic spectroscopy setup with operating electronics. The instrument described here is scheduled for launch end of 2017 aboard the TEXUS 54 sounding rocket as an important qualification step towards space application of iodine frequency references and related technologies. The payload will operate autonomously and its optical frequency will be compared to an optical frequency comb during its space flight.

Design and Qualification of Joints for ITER Magnet Busbar System

The joints connecting the ITER magnet busbars and coils utilize the twin-box “shaking hands” concept: inside a helium leak tight box, a bare cable is pressed in an indium-tinned copper base. To form the joint, two boxes are tightly compressed against each other on the copper side with a layer of indium in between. This concept was chosen to address the different requirements of the joints: to provide low electrical resistance without degradation and need of maintenance during ITER lifecycle, to sustain cyclic electromagnetic and pressure loads, to be easily dismountable in case of failure, to be tolerant to manufacturing and assembly misalignments, to provide low coolant flow impedance, and to limit ac losses and at the same time to facilitate current redistribution in the busbars. This paper presents the design; the key results of the electromagnetic, thermal, and stress analysis; and the major manufacturing and qualification steps. The latter includes cryogenic fatigue test of the joint welds and joint resistance measurements.

On-line qualification of a micro probing system for precision length measurement of micro-features on precision parts

This paper presents on-line qualification of the effective diameter of the micro-stylus tip ball of a micro probing system for precision length measurement of micro-features on precision parts by utilizing a set of gauge blocks as the qualification artefact, which is composed by one calibrated gauge block and two supporting gauge blocks that are wrung together for a good mechanical stability. The qualification artefact is aligned side by side with the precision part to be measured for enabling a rapid transfer between the qualification step of the probe two-point tip ball diameter and the length measurement step of the precision part. Based on the proposed setup, on-line qualifications of a micro-stylus with a nominal tip ball diameter of 52.6 μm were carried out by using two methods referred to as Method A and Method B, respectively. Method A is operated by probing the opposite sides of the gap between the two supporting gauge blocks separated by the calibrated gauge block, and Method B is operated by probing the opposite sides of the calibrated gauge block supported by the two supporting gauge blocks. Intensive uncertainty analyses based on the experimental results and the geometrical models were carried out to compare the performances of these two methods. Method A, which was confirmed to be more accurate and faster than Method B, was then employed to measure the width of a micro-gap on a precision part with compensation of the determined effective two-point tip ball diameter.

Qualification métrologique de spectrophotomètre : un guide pour les industriels

Spectrophotometers allow measurement of the optical properties of materials such as transmittance or reflectance. They are used in many industrial fields: health, transport, energy. . . To ensure the traceability of the measurements through the calibration of transmittance and reflectance standards, the LNE uses spectrophotometers that are qualified along the lifetime of these instruments. We present the qualification steps. The results are used to evaluate the uncertainties. The procedure followed can be used as a guideline for spectrophotometer users who want to evaluate their measurement uncertainties.