Quality Control Tool Research Articles

Label-Free Evaluation of Maturation and Hepatotoxicity of Human iPSC-Derived Hepatocytes Using Hyperspectral Raman Imaging.

To promote the clinical application of human induced pluripotent stem cell (hiPSC)-derived hepatocytes, a method capable of monitoring regenerative processes and assessing differentiation efficiency without harming or modifying these cells is important. Raman microscopy provides a powerful tool for this as it enables label-free identification of intracellular biomolecules in live samples. Here, we used label-free Raman microscopy to assess hiPSC differentiation into hepatocyte lineage based on the intracellular chemical content. We contrasted these data with similar phenotypes from the HepaRG and from commercially available hiPSC-derived hepatocytes (iCell hepatocytes). We detected hepatic cytochromes, lipids, and glycogen in hiPSC-derived hepatocyte-like cells (HLCs) but not biliary-like cells (BLCs), indicating intrinsic differences in biomolecular content between these phenotypes. The data show significant glycogen and lipid accumulation as early as the definitive endoderm transition. Additionally, we explored the use of Raman imaging as a hepatotoxicity assay for the HepaRG and iCell hepatocytes, with data displaying a dose-dependent reduction of glycogen accumulation in response to acetaminophen. These findings show that the nondestructive and high-content nature of Raman imaging provides a promising tool for both quality control of hiPSC-derived hepatocytes and hepatotoxicity screening.

Multi-Detection Size Exclusion Chromatography as an Advanced Tool for Monitoring Enzyme-Antibody Conjugation Reaction and Quality Control of a Final Product.

The multi-detection size exclusion chromatography (SEC) has been recognized as an advanced analytical technique for the characterization of macromolecules and process control, as well as the manufacturing and formulation of biotechnology products. It reveals reproducible molecular characterization data, such as molecular weight and its distribution, and the size, shape, and composition of the sample peaks. The aim of this work was to investigate the potential and suitability of the multi-detection SEC as a tool for surveillance over the molecular processes during the conjugation reaction between the antibody (IgG) and horseradish peroxidase (HRP), and demonstrate the plausibility of its application in the quality control of the final product, the IgG-HRP conjugate. Guinea pig anti-Vero IgG-HRP conjugate was prepared using a modified periodate oxidation method, based on periodate oxidation of the carbohydrate side chains of HRP, followed by the formation of Schiff bases between the activated HRP and amino groups of the IgG. The quantitative molecular characterization data of the starting samples, intermediates, and final product were obtained by multi-detection SEC. Titration of the prepared conjugate was performed by the ELISA and its optimal working dilution was determined. This methodology proved to be a promising and powerful technology for the IgG-HRP conjugate process control and development, as well as for the quality control of the final product, as verified by the analysis of several commercially available reagents.

Essential haematology for companion animal vets in first opinion practice

Haematology provides a vital source of diagnostic information in veterinary medicine. Advancement in technology has improved the availability of in-house automated analysers in first opinion practices, allowing practitioners quick access to complete blood count results to aid day-to-day clinical decisions. Most in-house analysers use flow cytometry or electrical impedence technologies which provide fairly accurate complete blood count results. However, practitioners must exercise care when interpreting these results as sample factors such as lipaemia, haemolysis, and the presence of atypical white blood cells, may have an effect on the accuracy of the results. Interpreting complete blood count results alongside a good quality blood smear is important, as it serves as a quality control tool to assess the accuracy of the complete blood count results and also provides useful information on the cell morphology. Good sample handling and good smear making technique are important to produce a blood smear of diagnostic value.

The role of a quality system in managing interface work

Introduction. This article shows the importance of quality control for construction projects during the implementation phase, as the use of an appropriate quality control plan for the project allows us to obtain the required quality of work for the first time without the need to rework or modify it and thus reduce the cost of the work. Addressing quality management as a necessary measure for achieving cost-effective construction processes, reducing waste, and minimizing losses resulting from its absence, its significance lies in the fact that adopting this approach in work will increase profits by controlling resources and costs. Additionally, considering the work methodology is essential.
 
 Materials and methods. The studied case is a three-storey villa project in Iraq. A quality control plan was developed for the implementation of the exterior coating of the type of stone facades, and after the completion of the work, quality control tools were used to check the quality of the coating implemented based on the plan, where the experimental approach was used.
 
 Results. The main aim of quality control is to ensure product quality and at the lowest possible cost. In practice, this can only be achieved by controlling the production processes, so we studied the stability of the implementation process through the usage of statistical quality control tools, and all the results indicated that the process is statistically disciplined and stable. Reducing the tasks and activities necessary to transform inputs (raw materials) into valuable products or services for customers is essential. Quality requires getting things right the first time, which means reducing defects or rework and, consequently, minimizing costs.
 
 Conclusions. A quality policy will lead to the correct use of resources and improve the quality of performance. It also has a positive impact on the overall cost of implementation within this study.

Prediction of the compressive strength of strain‐hardening cement‐based composites using soft computing models

AbstractStrain‐hardening cement‐based composites or engineered cementitious composites (ECC) is concrete produced using randomly distributed short polymer fibers. It is very ductile compared to conventional concrete. Compressive strength (CS) is a critical property used as a quality control tool to evaluate the strength of concrete implemented in the structural provisions and mix designs. Accordingly, to save cost and time for testing, it is essential to provide a predictive model to forecast the CS of the concrete mixtures using machine learning and modeling techniques. In this study, different modeling tools are used to propose analytical models to predict the CS of ECC mixtures, such as linear regression (LR), multi‐expression programming (MEP), artificial neural network (ANN), and Gaussian process regression (GPR). A total of 210 data were collected from the literature and used to train and test the developed model. The fly ash‐to‐cement ratio ranged from 0 to 5.6, water to binder ratio from 0.19 to 0.56, different superplasticizer and fiber content, and curing times of 1 to 180 days. Based on the evaluation of the developed models, the ANN model is superior to other developed models with a high coefficient of determination (R2), root mean squared error (RMSE), mean absolute error (MAE), and scatter index (SI). The sensitivity analysis of the input parameters' effect on the CS prediction indicates that the curing time and the fly ash‐to‐cement ratio are essential in forecasting ECC's CS.

A machine learning‐based quality control tool for functional MRI images

AbstractBackgroundChanges in functional MRI (fMRI) have been associated with Alzheimer’s disease and other neurological disorders. Quality control (QC) of images prior to their computational analysis is a key step in a clinical trial analysis workflow, and it is traditionally implemented visually by image analysts. However, the number of images acquired from large clinical studies makes neuroimaging QC a difficult task that diverts skilled resources and introduces inter‐rater variability. This problem is accentuated in fMRI, where image analysts need to visually inspect 4D sequences, and although image processing reports can be used as aid, the problem of having to inspect each report remains.MethodWe implemented an automated fMRI QC process using a stacking classifier (STC), random forest + support vector machine, with imaging quality metrics (IQM) as inputs. The IQMs were estimated with MRIQC. We also added a designed IQM that measures how centred the participant’s brain is within the image. As train/test dataset we used the ABIDE multisite database. For our experiments, only adult brains from the ABIDE database were used, leaving 14 sites available for a leave‐one‐site‐out (LOSO) cross‐validation experiment. All images included in the experiment were visually QC’d using validated protocols at IXICO.ResultThe LOSO validation procedure resulted in a mean pass‐vs‐fail accuracy of 92% (with 5.7% standard deviation, SD). Pass/fail sensitivity and specificity resulted in 97% (6.7% SD) and 69% (29% SD) respectively. We tested a fully trained STC model on an independent dataset of healthy ageing participants from OpenNeuro (ds002872), which resulted in 87% accuracy, 94% sensitivity and 50% specificity, which validates our modelling procedure.ConclusionIt is possible to design and deploy an automatic QC model for fMRI. Although sensitivity was high in all models from the LOSO experiments, specificity was on average low, highlighting the difficulty of detecting fails in a QC pipeline. However, the STC model can be deployed to detect clear passes that will not need visual QC, reliably reducing the number of cases that require visual inspection. Our future work will focus on testing our developed model on additional datasets (e.g. ADNI) to validate its performance before roll‐out to clinical trial applications.aging after age 90.

A case study on decentralized manufacturing of 3D printed medicines

Pharmaceutical 3D printing (3DP) is one of the emerging enabling technologies of personalised medicines as it affords the ability to fabricate highly versatile dosage forms. In the past 2 years, national medicines regulatory authorities have held consultations with external stakeholders to adapt regulatory frameworks to embrace point-of-care manufacturing. The proposed concept of decentralized manufacturing (DM) involves the provision of feedstock intermediates (pharma-inks) prepared by pharmaceutical companies to DM sites for manufacturing into the final medicine. In this study, we examine the feasibility of this model, with respect to both manufacturing and quality control. Efavirenz-loaded granulates (0–35%w/w) were produced by a manufacturing partner and shipped to a 3DP site in a different country. Direct powder extrusion (DPE) 3DP was subsequently used to prepare printlets (3D printed tablets), with mass ranging 266–371 mg. All printlets released more than 80% drug load within the first 60 min of the in vitro drug release test. An in-line near-infrared spectroscopy system was used as a process analytical technology (PAT) to quantify the printlets' drug load. Calibration models were developed using partial least squares regression, which showed excellent linearity (R2 = 0.9833) and accuracy (RMSE = 1.0662). Overall, this work is the first to report the use of an in-line NIR system to perform real-time analysis of printlets prepared using pharma-inks produced by a pharmaceutical company. By demonstrating the feasibility of the proposed distribution model through this proof-of-concept study, this work paves the way for investigation of further PAT tools for quality control in 3DP point-of-care manufacturing.

New indicators for commercial technical support development

Quality management has been developing and its application is feasible not only in control rooms and production-related departments. New techniques and control tools have been developed to seek a better level of customer and stakeholder satisfaction. The work in question is a case study of the application of quality control tools, more specifically of two performance indicators, to measure the efficiency of the technical support service to the commercial team provided by a large company in the food industry. The analysis of the data obtained showed that the indicators evaluated were effective in this task and allowed us to see opportunities for improvement in the performance of the service provided. From the results obtained and their analysis it was possible to verify that the proposed indicators are perfectly applicable, providing clear and objective answers, which allows for more precise decision making and focused on the company's objective.

Solid Oxide Cell Performance: Spatially Resolved Oxygen Electrode Stability

Several aspects of TNO SOC performance characteristics will be discussed, with a focus on steam electrolysis performance and lifetime behaviour during endurance tests of several thousand hours. Excellent steam electrolysis performance of the TNO SOE cells is observed at thermoneutral voltage, achieving current density values of −1.7 A/cm2 at an operating temperature of 750 °C. Lifetime assessment and material degradation of the SOC will be discussed, with a focus on the analysis of observed degradation phenomena in the oxygen electrode material. As oxygen electrode degradation can be critical for SOC performance in a stack environment, it is important to have a good understanding of the degradation processes and the ability to monitor them. At TNO, a novel approach of high-resolution 2D mapping of the lateral conductivity of the oxygen electrode has been used as an effective tool for quality control and validation of the oxygen electrode development. Additionally, the combination of 2D sheet resistance mapping, SEM-EDX and XRD techniques provides a powerful combination of tools to obtain a spatially resolved (3D) view of the localized degradation observed in the oxygen electrode after several thousand hours of steam electrolysis.

Signal-Decay Based Approach for Visualization of Buried Defects in 3-D Printed Ceramic Components Imaged with Help of Optical Coherence Tomography.

We propose the use of Optical Coherence Tomography (OCT) as a tool for the quality control of 3-D-printed ceramics. Test samples with premeditated defects, namely single- and two-component samples of zirconia, titania, and titanium suboxides, were printed by stereolithography-based DLP (Digital Light Processing) processes. The OCT tomograms obtained on the green samples showed the capability of the method to visualize variations in the layered structure of the samples as well as the presence of cracks and inclusions at depths up to 130 µm, as validated by SEM images. The structural information was visible in cross-sectional images as well as in plan-view images. The optical signal measured from the printed zirconia oxide and titanium oxide samples showed strong attenuation with depth and could be fit with an exponential decay curve. The variations of the decay parameter correlated very well with the presence of defects and material variation. When used as an imaging quantity, the decay parameter projects the position of the defects into 2-D (X,Y) coordinates. This procedure can be used in real time, it reduces the data volume up to 1000 times, and allows for faster subsequent data analysis and transfer. Tomograms were also obtained on sintered samples. The results showed that the method can detect changes in the optical properties of the green ceramics caused by sintering. Specifically, the zirconium oxide samples became more transparent to the light used, whereas the titanium suboxide samples became entirely opaque. In addition, the optical response of the sintered zirconium oxide showed variations within the imaged volume, indicating material density variations. The results presented in this study show that OCT provides sufficient structural information on 3-D-printed ceramics and can be used as an in-line tool for quality control.

Experimental determination and computational prediction of blend time in the USP dissolution testing Apparatus 1

The USP Apparatus 1 (rotating basket) is a preferred testing tool to evaluate the in vitro dissolution performance of pharmaceutical oral solid dosage forms, both as a quality control tool and to determine optimal drug formulations. The test relies on taking samples from the dissolution vessel during the dissolution process to obtain drug dissolution-time profiles. Of significant importance is the determination of the blend time, i.e., the time needed for the drug substance released from the dosage form to become dispersed throughout the vessel, especially at the sampling point. How representative these samples are with respect to the amount of drug dissolved can vary depending on operating and geometrical parameters. Here, the blend time in the USP Apparatus 1 was obtained experimentally and computationally for different operating conditions (basket mesh size, liquid fill volume, and rotation intensity) using the discoloration method coupled with image processing and by conducting time-dependent simulations using the Lattice-Boltzmann Large-Eddy Simulation approach. The experimental and predicted blend times were found to be in agreement. Additionally, an empirical correlation for blend time was developed. These results will help practitioners determine the effect of operating parameters on how representative the samples taken during the test are.

Portable near-infrared and Raman spectroscopic devices as complementary tools for instantaneous quality control of turmeric powder.

Process analytical technology (PAT) guidance is implemented in the quality assurance of phytocompounds to achieve the Industry 4.0 concept. Near-infrared (NIR) and Raman spectroscopies are feasible for rapid, reliable quantitative analysis through transparent packaging without removing the samples from their original containers. These instruments can serve PAT guidance. This study aimed to develop online portable NIR and Raman spectroscopic methods for quantifying total curcuminoids in turmeric samples through a plastic bag. The method mimicked an in-line measurement mode in PAT compared with placing samples into a glass vessel (at-line mode). Sixty-three curcuminoid standard-spiked samples were prepared. Then, 15 samples were randomly selected as fixed validation samples, and 40 of the 48 remaining samples were chosen as calibration set. The results obtained from the partial least square regression (PLSR) models constructed by using the spectra acquired from NIR and Raman were compared with the reference values from high-performance liquid chromatography (HPLC). The optimum PLSR model of at-line Raman was achieved with three latent variables and a root mean square error of prediction (RMSEP) of 0.46. Meanwhile, the PLSR model of at-line NIR with one latent variable offered an RMSEP of 0.43. For the in-line mode, PLSR models created from Raman and NIR spectra had one latent variable with RMSEP of 0.49 and 0.42, respectively. The R2 values for prediction were 0.88-0.92. The models established from the spectra from portable NIR and Raman spectroscopic devices with the appropriate spectral pretreatments allowed the determination of total curcuminoid contents through plastic bag.

Imaged capillary isoelectric focusing associated with multivariate analysis: A powerful tool for quality control of therapeutic monoclonal antibodies

Monoclonal antibodies are increasingly used in cancer therapy. To guarantee the quality of these mAbs from compounding to patient administration, characterization methods are required (e.g. identity). In a clinical setting, these methods must be fast and straightforward. For this reason, we investigated the potential of image capillary isoelectric focusing (icIEF) combined with Principal Component Analysis (PCA) and Partial least squares-discriminant analysis (PLS-DA). icIEF profiles obtained from monoclonals antibodies (mAbs) analysis have been pre-processed and the data submitted to principal component analysis (PCA). This pre-processing method has been designed to avoid the impact of concentration and formulation. Analysis of four commercialized mAbs (Infliximab, Nivolumab, Pertuzumab, and Adalimumab) by icIEF-PCA led to the formation of four clusters corresponding to each mAb. Partial least squares-discriminant analysis (PLS-DA) applied to these data allowed us to build models to predict which monoclonal antibody is analyzed. The validation of this model was obtained from k-fold cross-validation and prediction tests. The selectivity and the specificity of the model performance parameters were assessed by the excellent classification obtained. In conclusion, we established that the combination of icIEF and chemometric approaches is a reliable approach for unambiguously identifying compounded therapeutic monoclonal antibodies (mAbs) before patient administration.

Development of Simple VU Spectrophotometric Method for the Estimation of Bambuterol Hydrochloride in Bulk and Its Formulations

A simple, rapid and highly sensitive spectrophotometric method has developed for the estimation of Bambuterol hydrochloride in bulk and marketed tablet dosage form. In distilled water, Bambuterol showed absorbance at 264nm. Linearity was observed in the conc range of 200-1000 μg/ml (r2 = 0.9990). The assay results were found to be in a good agreement with label claim. The recovery studies were carried at 3 different levels i.e, at 100%, 150%, 200%. The accuracy of the method was conformed by recovery studies of tablet dosage forms and was found to be 96.43% for bambuterol hydrochloride. The method was validated stastically and by good recovery with % RSD is less than 2Thus the proposed method was found to be rapid, specific, precise, accurate and cost-effective quality control tool for the routine analysis of bambuterol hydrochloride in bulk and combined dosage form.

Multi-residue method to determine selected personal care products from five classes in fish based on miniaturized matrix solid-phase dispersion and solid-phase microextraction coupled to gas chromatography-mass spectrometry

A method featuring matrix solid-phase dispersion combined with solid-phase microextraction coupled to gas chromatography-mass spectrometry was developed to determine parabens, musks, antimicrobials, UV filters, and an insect repellent in fish. Optimization and validation of the method was carried out on tilapia and salmon samples. Acceptable linearity (R2 > 0.97), precision (relative standard deviations < 13 %) and accuracy (recovery > 80 %) at two concentration levels for all analytes were obtained using both matrices. The limits of detection ranged from 0.01 to 1.01 μg g−1 (wet weight) for all analytes except for methyl paraben. The SPME Arrow format was applied to increase the sensitivity of the method, and yielded detection limits more than ten times lower than those achieved with traditional SPME. The miniaturized method can be applied to various fish species, regardless of their lipid content, and represents a useful tool for quality control and food safety purposes.

Distinguishing between DNA-Loaded Full and Empty Capsids of Adeno-Associated Virus with Atomic Force Microscopy Imaging.

Recently, miraculous therapy approaches involving adeno-associated virus (AAV) for incurable diseases such as spinal muscular atrophy and inherited retinal dysfunction have been introduced. Nonreplicative, nonpathogenic, low rates of chromosome insertional properties and the existence of neutralizing antibodies are main safety reasons why the FDA approved its use in gene delivery. To date, AAV production always results in a mixture of nontherapeutic (empty) and therapeutic (DNA-loaded) full capsids (10-98%). Such existence of empty viral particles inevitably increases viral doses to human. Thus, the rapid monitoring of empty capsids and reducing the empty-to-full ratio are critical in AAV science. However, transmission electron microscopy (TEM) is the primary tool for distinguishing between empty and full capsids, which creates a research bottleneck because of instrument accessibility and technical difficulty. Herein, we demonstrate that atomic force microscopy (AFM) can be an alternative tool to TEM. The simple, noncontact-mode imaging of AAV particles allows the distinct height difference between full capsids (∼22 nm) and empty capsids (∼16 nm). The sphere-to-ellipsoidal morphological distortion observed for empty AAV particles clearly distinguishes them from full AAV particles. Our study indicates that AFM imaging can be an extremely useful, quality-control tool in AAV particle monitoring, which is beneficial for the future development of AAV-based gene therapy.

Quality by Design (QBD) Tool for Quality Control in Pharmaceutical Industry

Multiple approaches are operating in the modern world to analyze pharmaceutical dosage forms, but Quality by design is one of the most prominent approaches that can be used. Quality must be built into the product or method during pharmaceutical or analytical development, per the Quality by Design (QbD) concept. Commonly, input factors affect the Quality of products and techniques. The system is highly dynamic and adaptable to the changing environment, with better efficiency and an enhanced level of manufacturing within it. The quality-by-design strategy is also more consistent in upholding the product's designs and quality characteristics. The paper aims to better organize information by understanding and studying the elements of Quality by design. The pharmaceutical sector places a strong emphasis on quality prospects while also improving productivity and product designs. The paper seeks to describe the design development and study its multiple factors.

Assessment and analysis of internal losses in the manufacturing of products at machine-building enterprises

A new algorithm for determining internal losses in relation to engineering products is presented, mathematical dependencies are given for estimating of the categories of internal losses. On the example of the production of crankshafts, a classification of internal losses from defects is developed, the selection of quality control tools for registering types of defects and their further analysis is substantiated. A new form of a checklist is developed for recording non-conformities and losses from rejects. The final assessment of internal losses was carried out according to quantitative and cost criteria using the Pareto diagram. Keywords: internal losses, defects, repairable reject, irreparable reject, checklist, Pareto diagram, methodology for estimating of internal losses. metr@rgau-msha.ru

Development &amp; determination of UV method for sildenafil &amp; fluxetine in bulk drug &amp; in formulation

A simple, rapid, precise and highly selective spectrophotometric method was developed for simultaneous estimation of Sildenafil citrate and Fluoxetine Hydrochloride in tablet dosage form. This method, involves the measurement of absorbances of Sildenafil citrate and Fluoxetine Hydrochloride at the wavelengths of 282nm (λmax of Sildenafil citrate) and 249 nm (λmax of Fluoxetine Hydrochloride). Methanol was used as solvent. Linearity was observed in the concentration range of 10-18µg/ml for Sildenafil citrate and 3-8ug/ml. Fluoxetine Hydrochloride. The accuracy of the method was confirmed by recovery studies of tablet dosage forms and was found to be 98.1% and 99.2% for Sildenafil citrate and Fluoxetine Hydrochloride respectively. The method showed good reproducibility and recovery with % RSD less than 2. Thus, the proposed method was found to be rapid, specific, precise, accurate and cost-effective quality control tool for the routine analysis of Sildenafil citrate and Fluoxetine Hydrochloride in bulk and combined dosage form. A rapid and simple derivative spectrophotometric method was developed for simultaneous determination of Sildenafil citrate and Fluoxetine Hydrochloride in tablet dosage form. This method involves second order derivative spectroscopy using 282 nm and 249 nm as zero crossing points for Sildenafil citrate and Fluoxetine Hydrochloride respectively in methanol. Linearity was observed in the concentration range of 10-18µg/ml for Sildenafil citrate and 3-8ug/ml for Fluoxetine Hydrochloride. The accuracy of the method was found to be 98.21% and 99.2% for Sildenafil citrate and Fluoxetine Hydrochloride respectively. The method showed good reproducibility and recovery with % RSD less than 2.Thus, the proposed method was found to be rapid, specific, precise, accurate and cost-effective quality control tool for the routine analysis of sildenafil citrate and Fluoxetine Hydrochloride in bulk and combined dosage form. A selective, precise, isocratic and accurate stability indicating reverse phase high performance liquid chromatographic method was developed for the simultaneous determination of Sildenafil citrate and Fluoxetine Hydrochloride in the tablet dosage form. The method was validated for the linearity, accuracy, precision, robustness, system suitability as per ICH guidelines. Sildenafil citrate and Fluoxetine Hydrochloride were found to be linear in the range of 10-100 and 10-18µg/ml and 3-8ug/ml with the recoveries of 98.6% and 99.2%. The method was also applied for the determination of sildenafil citrate and Fluoxetine Hydrochloride in the presence of their degradation products formed under variety of stress conditions.

Penerapan Metode Six Sigma Dengan Konsep DMAIC Sebagai Alat Pengendalian Kualitas Produk

This study aims to determine the value of sigma before improvement is carried out and find out the causes of defects in the production process, as well as produce proposals for improvement and quality control of products. The population in this study was Arsel furniture table products during April 2015 to March 2016 which amounted to 420 products. Sampling using purposive sampling techniques and with the considerations used, the number of samples used was 306 samples. The results of research using the Six Sigma method with the DMAIC concept as a product quality control tool in Arsel Mebel found defective products in the form of rupture during cutting, removal of laminate materials, size errors, and the process of drilling table legs. The results of the analysis showed that the defective product that was more dominant was broken at the time of cutting, which was 38 percent.