A Framework for Cloud Validation in Pharma

The pharmaceutical industry’s increasing adoption of cloud-based technologies has introduced new challenges in computerized systems validation (CSV). This paper explores the evolving landscape of cloud validation in pharmaceutical manufacturing, focusing on ensuring data integrity and regulatory compliance in the digital era. We examine the unique characteristics of cloud-based systems and their implications for traditional validation approaches. A comprehensive review of current regulatory frameworks, including FDA and EMA guidelines, provides context for discussing cloud-specific validation challenges. The paper introduces a risk-based approach to cloud CSV, detailing methodologies for assessing and mitigating risks associated with cloud adoption in pharmaceutical environments. Key considerations for maintaining data integrity in cloud systems are analyzed, particularly when applying ALCOA+ principles in distributed computing environments. The article presents strategies for adapting traditional Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ) models to cloud-based systems, highlighting the importance of continuous validation in dynamic cloud environments. The paper also explores emerging trends, including integrating artificial intelligence and edge computing in pharmaceutical manufacturing and their implications for future validation strategies. This research contributes to the evolving body of knowledge on cloud validation in pharmaceuticals by proposing a framework that balances regulatory compliance with the agility offered by cloud technologies. The findings suggest that while cloud adoption presents unique challenges, a well-structured, risk-based approach to validation can ensure the integrity and compliance of cloud-based systems in pharmaceutical manufacturing.

Modeling and Validation of Diamagnetic Rotor Levitated by Permanent Magnetics

As an innovative,low-power consuming,and low-stiffness suspension approach,the diamagnetic levitation technique has attracted considerable interest because of its potential applicability in miniaturized mechanical systems.The foundation of a diamagnetic levitation system is mathematical modeling,which is essential for operating performance optimization and stability prediction.However,few studies on systematic mathematical modeling have been reported.In this study,a systematic mathematical model for a disc-shaped diamagnetically levitated rotor on a permanent magnet array is proposed.Based on the proposed model,the magnetic field distribution characteristics,diamagnetic levitation force characteristics(i.e.,levitation height and stiffness),and optimized theoretical conditions for realizing stable levitation are determined.Experiments are conducted to verify the feasibility of the proposed mathematical model.Theoretical predictions and experimental results indicate that increasing the levitation height enlarges the stable region.Moreover,with a further increase in the rotor radius,the stable regions of the rotor gradually diminish and even vanish.Thus,when the levitation height is fixed,a moderate rotor radius permits stable levitation.This study proposes a mathematical modeling method for a diamagnetic levitation system that has potential applications in miniaturized mechanical systems.

An internal ballistic model of electromagnetic railgun based on PFN coupled with multi-physical field and experimental validation

To accelerate the practicality of electromagnetic railguns,it is necessary to use a combination of threedimensional numerical simulation and experiments to study the mechanism of bore damage.In this paper,a three-dimensional numerical model of the augmented railgun with four parallel unconventional rails is introduced to simulate the internal ballistic process and realize the multi-physics field coupling calculation of the rail gun,and a test experiment of a medium-caliber electromagnetic launcher powered by pulse formation network(PFN)is carried out.Various test methods such as spectrometer,fiber grating and high-speed camera are used to test several parameters such as muzzle initial velocity,transient magnetic field strength and stress-strain of rail.Combining the simulation results and experimental data,the damage condition of the contact surface is analyzed.

Adaptive Robust Servo Control for Vertical Electric Stabilization System of Tank and Experimental Validation

A tracking stability control problem for the vertical electric stabilization system of moving tank based on adaptive robust servo control is addressed.This paper mainly focuses on two types of possibly fast timevarying but bounded uncertainty within the vertical electric stabilization system:model parameter uncertainty and uncertain nonlinearity.First,the vertical electric stabilization system is constructed as an uncertain nonlinear dynamic system that can reflect the practical mechanics transfer process of the system.Second,the dynamical equation in the form of state space is established by designing the angular tracking error.Third,the comprehensive parameter of system uncertainty is designed to estimate the most conservative effects of uncertainty.Finally,an adaptive robust servo control which can effectively handle the combined effects of complex nonlinearity and uncertainty is proposed.The feasibility of the proposed control strategy under the practical physical condition is validated through the tests on the experimental platform.This paper pioneers the introduction of the internal nonlinearity and uncertainty of the vertical electric stabilization system into the settlement of the tracking stability control problem,and validates the advanced servo control strategy through experiment for the first time.

Direct Pointwise Comparison of FE Predictions to StereoDIC Measurements:Developments and Validation Using Double Edge-Notched Tensile Specimen

To compare finite element analysis(FEA)predictions and stereovision digital image correlation(StereoDIC)strain measurements at the same spatial positions throughout a region of interest,a field comparison procedure is developed.The procedure includes(a)conversion of the finite element data into a triangular mesh,(b)selection of a common coordinate system,(c)determination of the rigid body transformation to place both measurements and FEA data in the same system and(d)interpolation of the FEA nodal information to the same spatial locations as the StereoDIC measurements using barycentric coordinates.For an aluminum Al-6061 double edge notched tensile specimen,FEA results are obtained using both the von Mises isotropic yield criterion and Hill’s quadratic anisotropic yield criterion,with the unknown Hill model parameters determined using full-field specimen strain measurements for the nominally plane stress specimen.Using Hill’s quadratic anisotropic yield criterion,the point-by-point comparison of experimentally based full-field strains and stresses to finite element predictions are shown to be in excellent agreement,confirming the effectiveness of the field comparison process.

Development and validation of a circulating tumor DNA-based optimization-prediction model for short-term postoperative recurrence of endometrial cancer

BACKGROUND Endometrial cancer(EC)is a common gynecological malignancy that typically requires prompt surgical intervention;however,the advantage of surgical management is limited by the high postoperative recurrence rates and adverse outcomes.Previous studies have highlighted the prognostic potential of circulating tumor DNA(ctDNA)monitoring for minimal residual disease in patients with EC.AIM To develop and validate an optimized ctDNA-based model for predicting shortterm postoperative EC recurrence.METHODS We retrospectively analyzed 294 EC patients treated surgically from 2015-2019 to devise a short-term recurrence prediction model,which was validated on 143 EC patients operated between 2020 and 2021.Prognostic factors were identified using univariate Cox,Lasso,and multivariate Cox regressions.A nomogram was created to predict the 1,1.5,and 2-year recurrence-free survival(RFS).Model performance was assessed via receiver operating characteristic(ROC),calibration,and decision curve analyses(DCA),leading to a recurrence risk stratification system.RESULTS Based on the regression analysis and the nomogram created,patients with postoperative ctDNA-negativity,postoperative carcinoembryonic antigen 125(CA125)levels of<19 U/mL,and grade G1 tumors had improved RFS after surgery.The nomogram’s efficacy for recurrence prediction was confirmed through ROC analysis,calibration curves,and DCA methods,highlighting its high accuracy and clinical utility.Furthermore,using the nomogram,the patients were successfully classified into three risk subgroups.CONCLUSION The nomogram accurately predicted RFS after EC surgery at 1,1.5,and 2 years.This model will help clinicians personalize treatments,stratify risks,and enhance clinical outcomes for patients with EC.

Method Development and Validation of the Simultaneous Analysis of Methylisothiazolinone, Methylchloroisothiazolinone, Benzisothiazolinone and Bronopol in Washing-Up Liquid

A method of analysis for the simultaneous determination of methylisothiazolinone (MI), methylchloroisothiazolinone (CMI), benzisothiazolinone (BIT) and Bronopol (BNP) in washing-up liquid was established. The method consisted of a gradient HPLC analysis at three different wavelengths. The four compounds could be analyzed with good precision and accuracy.

Development and Validation of a UPLC Method for the Determination of Docetaxel and Its Related Substances in Pharmaceutical Dosage Forms, an Antineoplastic Agent

A novel, simple, and sensitive Ultra Performance Liquid Chromatography (UPLC) method was developed and validated for the quantification of process-related impurities and degradants, as well as the assay of Docetaxel. The stability-indicating capability of the method was demonstrated through forced degradation studies and a comprehensive mass balance evaluation. Chromatographic separation was achieved using an ACQUITY UPLC BEH C18 column (100 × 2.1 mm, 1.7 µm), with gradient elution. The mobile phase A comprised a mixture of water, methanol, and acetonitrile (500:300:200, v/v/v), while mobile phase B was acetonitrile and water (800:200, v/v). The flow rate was set at 0.4 mL/min, with detection at 232 nm using a photodiode array detector. The method exhibited excellent performance, with a tailing factor of 1.10 for Docetaxel. The method was rigorously validated for precision, accuracy, linearity, LOD, LOQ, ruggedness, specificity, and robustness. Forced degradation studies confirmed the method’s suitability for stability analysis. Stability testing on the drug substance was conducted following ICH guidelines.

Robustness Study and Superior Method Development and Validation for Analytical Assay Method of Atropine Sulfate in Pharmaceutical Ophthalmic Solution

Background: The robustness is a measurement of an analytical chemical method and its ability to contain unaffected by little with deliberate variation of analytical chemical method parameters. The analytical chemical method variation parameters are based on pH variability of buffer solution of mobile phase, organic ratio composition changes, stationary phase (column) manufacture, brand name and lot number variation;flow rate variation and temperature variation of chromatographic system. The analytical chemical method for assay of Atropine Sulfate conducted for robustness evaluation. The typical variation considered for mobile phase organic ratio change, change of pH, change of temperature, change of flow rate, change of column etc. Purpose: The aim of this study is to develop a cost effective, short run time and robust analytical chemical method for the assay quantification of Atropine in Pharmaceutical Ophthalmic Solution. This will help to make analytical decisions quickly for research and development scientists as well as will help with quality control product release for patient consumption. This analytical method will help to meet the market demand through quick quality control test of Atropine Ophthalmic Solution and it is very easy for maintaining (GDP) good documentation practices within the shortest period of time. Method: HPLC method has been selected for developing superior method to Compendial method. Both the compendial HPLC method and developed HPLC method was run into the same HPLC system to prove the superiority of developed method. Sensitivity, precision, reproducibility, accuracy parameters were considered for superiority of method. Mobile phase ratio change, pH of buffer solution, change of stationary phase temperature, change of flow rate and change of column were taken into consideration for robustness study of the developed method. Results: The limit of quantitation (LOQ) of developed method was much low than the compendial method. The % RSD for the six sample assay of developed method was 0.4% where the % RSD of the compendial method was 1.2%. The reproducibility between two analysts was 100.4% for developed method on the contrary the compendial method was 98.4%.

Method Verification and Validation of Hydralazine Hydrochloride: Spectrophotometric Analysis in Pure and Pharmaceutical Formulations

The new method proposed is based on the formation of hydralazine-Bromophenol blue ion pair simply and without further extraction or heating. The ion pair was prepared in the presence of pH 3 citrate buffer forming a yellow-colored chromogen. A new maximum UV-visible band formed at 416 nm. The color was stable for more than 10 hours and obeyed Beer’s Law over the concentration range of 10 - 50 µg/mL. The calculated molar absorptivity and Sandell’s sensitivity were 1.01 × 104 L∙mol−1∙cm−1 and 0.0514 µg/mL, respectively. The elements of method validation stipulated by The International Conference on Harmonization [Q2 (R1)] were applied for hydralazine hydrochloride assay in pure and pharmaceutical tablet formulation. The average recoveries of the pure solution and the pharmaceutical formulation were 98.94% and 99.50%, respectively. The results were statistically compared by F-test, which indicates that the method can be precise and repeatable for both pure and pharmaceutical solutions. The method was found to be accurate, reproducible, and cost-effective, and validated for the assay of hydralazine in terms of the routine quality control.

Validation of a Method for Characterization of Ethanol in Water by HS-GC-FID to Serve the Traceability of Halal Measurements

The determination of the ethanol content in food products is of fundamental importance for HALAL certification. In this work, an analytical method for the determination of ethanol in water by headspace gas chromatography with flame ionization detector (HS-GC-FID) has been developed and validated for the use in characterization of ethanol reference materials. The validation study was carried out in the linear calibration range 100 - 1500 mg/kg using the NIST SRM 2900, nominal 95.6%. The studied performance characteristics of the method were the limit of detection, LOD, the limit of quantification LOQ, selectivity, linearity, precision, recovery and bias. The validation results showed that the method is selective, precise, accurate and free from any significant bias. The LOD and LOQ were 1.27 and 3.86 mg/kg respectively and the estimated expanded uncertainty was 2% indicating that the method is fit for the purpose of certification of ethanol in water reference materials.

Development and validation of an instrument to assess knowledge,attitudes,and practices on digital health among nursing officers

Objective:Validation is an important aspect of an instrument,and it ensures the confidence of researchers to employ the instrument in their studies.This study was conducted to develop and validate an instrument to assess knowledge,attitudes,and practices(KAP) on digital health among nurses since digital health capacity is a major concern in health care that needs to be assessed.Methods:We conducted a methodological study to assess the content validity and reliability of the instrument.First,items were generated through a comprehensive literature review and by obtaining an expert opinion.Second,content and face validity were assessed by a panel of 7 experts.Both the item-level content validity index(I-CVI) and the scale-level content validity index(S-CVI) were established.Moreover,test–retest reliability and internal consistency of the instrument were assessed.Data were analyzed using SPSS version 25.Results:The initial pool consisted of 60 items and after obtaining content,face,and construct validity,51 items remained.Items with an I-CVI <0.78 were considered relevant.The S-CVI for relevancy,clarity,ambiguity,and simplicity were 0.93,0.91,0.94,and 0.92,respectively.Five subcomponents were constructed in each knowledge and attitudes domain,and the test–retest reliability test revealed that the instrument has good reliability,showing correlation coefficient values for the KAP domains and the total questionnaire of 0.76,0.98,0.99,and 0.99,respectively.The independent Cronbach's α for all items was 0.76,indicating good internal consistency.Conclusions:The present study established the acceptable validity and ensured the good reliability and internal consistency of the instrument,which can serve as an assessment tool of KAP on digital health among healthcare professionals.

Development and validation of a novel questionnaire regarding vision screening among preschool teachers in Malaysia

AIM:To develop and evaluate the validity and reliability of a knowledge,attitude,and practice questionnaire related to vision screening(KAP-VST)among preschool teachers in Malaysia.METHODS:The questionnaire was developed through a literature review and discussions with experts.Content and face validation were conducted by a panel of experts(n=10)and preschool teachers(n=10),respectively.A pilot study was conducted for construct validation(n=161)and test-retest reliability(n=60)of the newly developed questionnaire.RESULTS:Based on the content and face validation,71 items were generated,and 68 items were selected after exploratory factor analysis.The content validity index for items(I-CVI)score ranged from 0.8-1.0,and the content validity index for scale(S-CVI)/Ave was 0.99.Internal consistency was KR^(2)0=0.93 for knowledge,Cronbach’s alpha=0.758 for attitude,and Cronbach’s alpha=0.856 for practice.CONCLUSION:The KAP-VST is a valid and reliable instrument for assessing knowledge,attitude,and practice in relation to vision screening among preschool teachers in Malaysia.

Optimization and Validation of a Simple Spectrophotometric Based DPPH Method for Analysis of Antioxidant Activity in Aerated, Semi-Aerated and Non-Aerated Tea Products

In this study, the simple DPPH UV-spectrophotometric analytical procedures were optimized and validated for the estimation of antioxidant properties in aerated, semi-aerated and non-aerated tea products as per the AOAC guidelines. The method was found to be simple, rapid, accurate and economical in estimating antioxidant properties in the different tea products. A (0.0100 ± 0.0001) g well ground tea sample was extracted directly in 80% v/v methanol in distilled water. The precision of the method had an RSD% of 1.695 with a linear relation equation of Y = 200.7X + 5.25 (r2 = 0.997). The method proved to be a reliable and effective tool in analysis of anti-oxidant properties in varied tea cultivars and their processed products.

Wheel-rail contact model for railway vehicle-structure interaction applications:development and validation

An enhancement in the wheel-rail contact model used in a nonlinear vehicle-structure interaction(VSI)methodology for railway applications is presented,in which the detection of the contact points between wheel and rail in the concave region of the thread-flange transition is implemented in a simplified way.After presenting the enhanced formulation,the model is validated with two numerical applications(namely,the Manchester Benchmarks and a hunting stability problem of a sus-pended wheelset),and one experimental test performed in a test rig from the Railway Technical Research Institute(RTRI)in Japan.Given its finite element(FE)nature,and contrary to most of the vehicle multibody dynamic commercial software that cannot account for the infrastructure flexibility,the proposed VSI model can be easily used in the study of train-bridge systems with any degree of complexity.The validation presented in this work proves the accuracy of the proposed model,making it a suitable tool for dealing with different railway dynamic applications,such as the study of bridge dynamics,train running safety under different scenarios(namely,earthquakes and crosswinds,among others),and passenger riding comfort.

Modelling,Validation,and Calculations of Stratospheric Ozone Dynamics and Latitudinal Changes

This paper presents an engineering system approach of 2-D cylindrical model of mass balance calculations with convection,diffusion,and all potential photolysis,ozone generating and depleting chemical reactions considered.This model was developed,validated,and tested under different conditions for the stratospheric ozone.The calculated ozone concentrations and profile in the stratosphere at both the Equator and mid-latitudinal location of 40°S were found to exhibit a similar and close profile and peak value of the published measured data.The discrepancy between the calculations and measurements for the average ozone concentration was shown to be less than 1%and the variation of distributions to be less than 19%.The latitudinal changes of ozone concentrations,distribution,and peak of the layer were found to shift from 9.41 ppm at mid-altitude of z=30 km at the Equator,to 7.81 ppm at z=34.5 km at 40°S,to 5.78 ppm at higher altitude z=39 km at the South Pole.The total ozone abundances at strategic latitudes at 0°S,20°S,40°S,60°S,and 90°S,were found to remain stable and not much changed,from 305 DU to 335 DU,except a smaller value of 288 DU at the South Pole.The possible explanations of ozone profile change and peak shifting as affected by solar/UV radiation,latitudinal locations,and ozone-depleting reactions were discussed and elaborated.The 2-D ozone Model presented in this paper is a robust,efficient,executable,and validated model for studying the complex ozone phenomena in the stratosphere.

Solriamfetol impurities:Synthesis,characterization,and analytical method(UPLC-UV)validation

Given that impurities may affect the quality and safety of drug products,impurity identification and profiling is an integral part of drug quality control and is particularly important for newly developed medications such as solriamfetol,which is used to treat excessive daytime sleepiness.Although the highperformance liquid chromatography analysis of commercial solriamfetol has revealed the presence of several impurities,their synthesis,structure elucidation,and chromatographic determination have not been reported yet.To bridge this gap,we herein identified,synthesized,and isolated eight processrelated solriamfetol impurities,characterized them using spectroscopic and chromatographic techniques,and proposed plausible mechanisms of their formation.Moreover,we developed and validated a prompt impurity analysis method based on ultrahigh-performance liquid chromatography with UV detection,revealing that its selectivity,linearity,accuracy,precision,and quantitation limit meet the acceptance criteria of method validation stipulated by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use.Thus,the developed method was concluded to be suitable for the routine analysis of solriamfetol substances.

Prediction of ground-borne vibration induced by impact pile driving:numerical approach and experimental validation

Deep foundations are currently used in engineering practice to solve problems caused by weak geotechnical characteristics of the ground.Impact pile driving is an interesting and viable solution from economic and technical points of view.However,it is necessary to ensure that the environmental drawbacks,namely ground-borne vibration,are adequately met.For this purpose,the authors propose an axisymmetric finite element method-perfectly matched layer(FEM-PML)approach,where the nonlinear behavior of the soil is addressed through an equivalent linear methodology.Given the complexity of the problem,an experimental test site was developed and fully characterized.The experimental work comprised in-situ and laboratory soil characterization,as well as the measurement of vibrations induced during pile driving.The comparison between experimental and numerical results demonstrated a very good agreement,from which it can be concluded that the proposed numerical approach is suitable for the prediction of vibrations induced by impact pile driving.The experimental database is available as supplemental data and may be used by other researchers in the validation of their prediction models.

Validation of the multi-satellite merged sea surface salinity in the South China Sea

Sea surface salinity(SSS)is an essential variable of ocean dynamics and climate research.The Soil Moisture and Ocean Salinity(SMOS),Aquarius,and Soil Moisture Active Passive(SMAP)satellite missions all provide SSS measurements.The European Space Agency(ESA)Climate Change Initiative Sea Surface Salinity(CCI-SSS)project merged these three satellite SSS data to produce CCI L4SSS products.We validated the accuracy of the four satellite products(CCI,SMOS,Aquarius,and SMAP)using in-situ gridded data and Argo floats in the South China Sea(SCS).Compared with in-situ gridded data,it shows that the CCI achieved the best performance(RMSD:0.365)on monthly time scales.The RMSD of SMOS,Aquarius,and SMAP(SMOS:0.389;Aquarius:0.409;SMAP:0.391)are close,and the SMOS takes a slight advantage in contrast with Aquarius and SMAP.Large discrepancies can be found near the coastline and in the shelf seas.Meanwhile,CCI with lower RMSD(0.295)perform better than single satellite data(SMOS:0.517;SMAP:0.297)on weekly time scales compared with Argo floats.Overall,the merged CCI have the smallest RMSD among the four satellite products in the SCS on both weekly time scales and monthly time scales,which illustrates the improved accuracy of merged CCI compared with the individual satellite data.

Validation and accuracy analysis of wind products from scatterometer onboard the HY-2B satellite

The Chinese marine dynamic environment satellite HY-2B was launched in October 2018 and carries a Ku-band scatterometer.This paper focuses on the accuracies of HY-2B scatterometer wind data during the period from November 2018 to May 2021.The HY-2B wind data are validated against global moored buoys operated by the U.S.National Data Buoy Center and Tropical Atmosphere Ocean,numerical model data by the National Centers for Environmental Prediction,and the Advanced Scatterometer data issued by the Remote Sensing System.The results showed that the wind speeds and directions observed by the HY-2B scatterometer agree well with these buoy wind measurements.The root-mean-squared errors(RMSEs)of the HY-2B wind speed and direction are 0.74 m/s and 11.74°,respectively.For low wind speeds(less than 5 m/s),the standard deviation of the HY-2B-derived wind direction is higher than 20°,which implies that the HY-2B wind direction for low wind speeds is less accurate than that for moderate to high wind speed ranges.The RMSE of the HY-2B wind speed is slightly larger in high latitude oceans(60°–90°S and 60°–90°N)than in low latitude regions.Furthermore,the dependence of the residuals on the cross-track location of wind vector cells and the stability of the HY-2B scatterometer wind products are discussed.The wind stability assessment results indicate that a clear yearly oscillation is observed for the HY-2B wind speed bias which is due to seasonal weather variations.In general,the accuracy of HY-2B winds meets the operational precision requirement and is consistent with other wind data.