Instrument Qualification Research Articles

Питання вибору і кваліфікації засобів розробки програмного забезпечення для електронних систем автоматичного керування авіаційних двигунів

The introductory part of the article provides information that Element JSC is one of the leading enterprises in Ukraine in the scientific and technical direction "Electronic systems for measuring, parameters monitoring and controlling aircraft engines". Because of cooperation with Ivchenko-Progress SE and Motor Sich JSC, Element JSC has manufactured more than 250 EEC units of the RDC-450M family for various modifications of the AI-450 Turboshaft/Turboprop engines. The software of these EEC units is certified according to the DO-178B/ED-12B. The software of subsequent EEC units under development is planned to be certified according to the state-of-the-art DO-178C/ED-12С guideline, and development tools qualified according to the DO-330/ED-215 guideline will also be used in development. This article is devoted to the issues of selection and qualification of such tools. A review and brief analysis of modern commercial software development tools for embedded systems, including those applied to the STM32 family microcontrollers, which are widely used in the JSC Element products, is given. The qualification of the user required for operating these development tools is indicated. Information is given on software verification tools, features of the interpretation of the “verification” term in DO-178C/ED-12C. As an example, the SPI tool is given, which has been successfully used for many years at Element JSC for the functional development of EEC units. The process of determining the level of qualification of instruments using three special criteria is described, an algorithm for qualification is given, and examples from the practice of Element JSC are given. Information is given on recently appearing commercial DO-178 support packages for embedded software developers in the qualification of tools, an algorithm of operation is given, shortcomings and possible problems are assessed. Finally, it is concluded that the process of selecting and further qualification of tools has a serious impact on labor costs in the certification of software for embedded systems for aviation applications.

Evolution of policy instruments for food safety risk management: Comparing China and Western countries

Using text mining and instrument qualification techniques based on 605 policy instrument texts issued by the China government from 1985 to 2019, this study quantitatively analyzes the total number, type structure, specific composition, and evolution of policy instruments for food safety risks governance. Overall, 1,193, 459, and 95 of these instruments were compulsory, mixed, and voluntary, respectively. The results found that the evolution of these instruments in China exhibits a strong similarity to those in Western countries. They both started with compulsory instruments alone, then turned to a combination of compulsory and mixed instruments, and eventually progressed to a mixture of compulsory, mixed, and voluntary instruments. The internal logic of this evolution is that the instrument type structure changes continuously in response to the changes in the stakeholder relationships among government, market, and society. However, unlike Western countries, China still relies heavily on the role of government, which results in the dominance of compulsory instruments and insufficiency of mixed and voluntary instruments, reflecting high path dependence. Implications are discussed. • Using text mining and instrument qualification techniques. • The internal logic is with the relationship among government, market, and society. • The evolution of instruments in China is similar in Western countries. • China exist structural imbalance among instruments.

Application of Elements of Quality by Design to Development and Optimization of HPLC Method for Fingolimod

Purpose: A HPLC method for Fingolimod was developed using a Quality by Design concept. QbD has gained importance in recent times due to regulatory requirements. Actual study was started after determination of target profile and qualification of instrument.
 Methods: Separation was carried on a Grace C-8 column (4.6 x 250 mm, 5-μm particle size).The composition of mobile phase was methanol and 20 mM ammonium formate buffer of pH5.8 in gradient mode HPLC method development is affected by critical factors like pH, flow rate and mobile phase composition.
 Results: To study the effects of these three factors on USP tailing, Box Behnken optimization model was applied. Desirability of the model was set at Tailing less than 1.2.Analysis of results was done using surface diagrams. Verification of Software generated results was done by taking six replicates of the run. Thus developed and optimised method was Finally validated as per ICH guideline.
 Conclusion: A Quality by Design approach has been successfully utilised in method development of the Fingolimod in bulk. All key aspect of QbD were tried to be implemented in said study.
 Systematic approach was utilized for method development which includes beginning with determination of target profile characteristics, instrument qualification, risk assessment, design of experiment and validation.
 Three factors i.e. Ph, flow rate and methanol concentration were analysed for their effect on USP tailing as a responce. Interaction and quadratic effect of the factors were studied with least possible runs by using Box Behnken model. Response surface diagrams and contour plots were studied for coming to conclusion which factors are affecting response and their limits were recorded. Optimum run condition was obtained; Replicates of run having optimized condition were taken to confirm the predicted response with actual response.

Is There a Leak in the OECD's Global Minimum Tax Proposals (GLOBE, Pillar Two)?

There might be a leak in the OECD’s global minimum tax proposals (GLOBE; Pillar Two). To address the remaining challenges of base erosion and profit shifting (BEPS) by large multinational enterprises the OECD envisages a global minimum level of company taxation and top-up taxation by countries up to that level where other countries do not adhere to the new standard. The objective is to reach political consensus mid this year within the Inclusive Framework, a tax policy discussion platform of the OECD uniting around 140 countries. A blueprint on the system’s technical design is currently being debated. If put in place as now devised the Pillar Two system may be prone to be gamed. Parties having an interest in this would be able to raise the minimum level at their discretion - without actually paying more tax - to accordingly circumvent the application of the top-up taxation mechanisms. The key lies in the strategic use of differences between tax accounting and commercial accounting, particularly those in relation to the qualification of financial instruments as debt or equity. Underneath lies the choice to base the Pillar Two system on transfer pricing and single-entity financials. If left unaddressed a new world of tax planning opportunities would likely emerge. Please read further below on how the planning would work, together with references to some alternative reform options to address the challenges raised in international company taxation.

Experimental Qualification of New Instrumentation for Lead-Lithium Eutectic in IELLLO Facility

• results of a new experimental campaign in IELLLO facility, a LLE (Lead Lithium Eutectic) loop designed for transient simulation and instrumentation testing. • A type of differential pressure transducer and 3 flow meters were characterized in LLE: Vortex flow meter, Coriolis flow meter, Thermal flow meter. • The differential pressure transducers were used to characterize the pressure drops of some of the major components and the pressure head of the permanent magnet pump. • After a detailed analysis, the thermal flow meter was considered the most reliable for flow rate measurements in LLE. • A detailed uncertainty analysis was carried out to support the investigations. The experimental facility IELLLO was installed in ENEA Brasimone R.C. in 2007, aiming to support the design of liquid Test Blanket Modules that will be installed in ITER and to contribute to the development of Lead-Lithium Eutectic (LLE) technologies. IELLLO has been recently upgraded by installing instrumentation relevant for ITER application. Differential pressure transducers, a Coriolis and a thermal mass flow meters were installed in the facility. An experimental campaign was planned, setting two objectives. The first objective was to qualify the instrumentation for flowing LLE The installation of a differential pressure transducer across each flow meter made also possible to characterize the pressure drops across these instruments. The second objective of this activity was to improve the knowledge on the performances of the main components of the loop at lower mass flow rates (namely 0.5-1.2 kg/s) and to quantify their pressure drops. The investigated flow rates were chosen to be relevant for the LLE loop of the WCLL TBS (Water Cooled Lead-Lithium Test Blanket System). This work presents the results of the experimental campaign, paying particular attention to underline the lessons learned on how to correctly operate instrumentation for LLE.

In-Cabinet Response Spectrum Generation Using Frequency Domain Analysis Method

Seismic qualification of instruments and devices mounted on electrical cabinets in a nuclear power plant is performed in this study by means of the in-cabinet response spectrum (ICRS). A simple method and two rigorous methods are proposed in the EPRI NP-7146-SL guidelines for generating the ICRS. The simple method of EPRI can give unrealistic spectra that are excessively conservative in many cases. In the past, the time domain analysis (TDA) methods have been mostly used to analyze a structure. However, the TDA requires the generation of an artificial earthquake input motion compatible to the target response spectrum. The process of generating an artificial earthquake may involve a great deal of uncertainty. In addition, many time history analyses should be performed to increase the accuracy of the results. This study developed a numerical analysis program for generating the ICRS by frequency domain analysis (FDA) method. The developed program was validated by the numerical study. The ICRS calculated by FDA thoroughly matched with those obtained from TDA. This study then confirms that the method it proposes can simply and efficiently generate the ICRS compared to the time domain method.

Current state of in-cabinet response spectra for seismic qualification of equipment in nuclear power plants

Many nuclear power plants in the south eastern region of South Korea are undertaking seismic qualification studies due to the recent earthquake in Gyeongju region. The records from this earthquake contain high frequency content compared to the frequency exhibited in most of the design basis Safe Shutdown Earthquakes used in the design of nuclear power plants. While the high frequency ground motions are not detrimental to the structures due to relatively smaller displacements, such motions can lead to functionality related failures in electrical equipment and systems such as control relays. The seismic qualification of relays and other such instruments require characterization of in-cabinet response spectra (ICRS) in the cabinet or control panels where they are mounted. The current practice of generating ICRS, in many cases, uses constant amplification factors which are based on studies containing low frequency ground motions. Cabinets can often have higher frequency modes which can amplify the motion if it contains high frequency pulses. Finite element analysis to evaluate the dynamic characteristics of cabinet is highly impractical because each cabinet is vastly different from other cabinets and a given plant contains hundreds of such cabinets and control panels. Therefore, a method is needed to evaluate accurate dynamic characteristics of cabinets and control panels in a relatively simple manner. This paper presents the details of such a method called Ritz vector approach and also compares the ICRS of an actual cabinet for a high frequency input motion with that for a low frequency input motion.

AN OVERVIEW OF ANALYTICAL INSTRUMENT QUALIFICATION WITH REFERENCE OF PHARMACEUTICAL INDUSTRY

In the most general sense, validation refers to a process that consists of at least four distinct components or steps: software, instruments, methods or procedures, and system suitability The system, the software, and the method must all be validated, and system suitability is used to keep the process in check. But while the overall process is called validation, some of the steps also are referred to by that same term, as well as other steps such as qualification and verification. Analytical instruments are used for a specific analysis. So regular performance verifications are made to ensure that the instrument to be used is suitable for its intended application. All equipments used in the production of products shall be properly Validated and Calibrated to demonstrate that it is suitable for its intended purpose. The current equipment qualification programs and procedures used within the pharmaceutical industry are based on regulatory requirements, voluntary standards, vendor practices, and industry practices. The result is considerable variation in the way pharmaceutical companies approach the qualification of laboratory equipment and the way they interpret the often vague requirements. The process for instrument qualification follows the 4Qs model approach. It include design qualification (DQ), Installation qualification (IQ), Operational qualification (OQ), Performance qualification (PQ). The goal of any regulated laboratory is to provide reliable and valid data suitable for its intended purpose. Analysts use validated methods, system suitability tests, and in-process quality control checks to ensure that the data they acquire are reliable and that there are specific guidance and procedures available to ensure compliance.
 Keywords: Qualification, FDA, Instruments, Validation, Calibration, Documentation

Qualification Strategy of New Technologies for Safety Instrumentation in Harsh Radiation Environments

Qualification of safety instrumentation for nuclear reactors is a challenging issue in harsh radiation environments; the task is further complicated when new technologies are introduced. In this paper, we present two qualification strategies for new developments qualified to the highest safety standards. In the first case study, we develop a qualification method that quantifies the aging rate of a polymer during different aging steps, thus paving the way to predictive maintenance for safety qualified instrumentation. In the second case study, we propose a qualification strategy for a fiber optic-based probe which is supposed to implement a safety function in an extreme radiation environment that will expose the probe to 800 MGy over its lifetime.

Performance qualification for reproducible Surface Plasmon Resonance analysis

Surface Plasmon Resonance Biosensors (SPR) are one of the most powerful tools to characterize protein binding, e.g. for drug discovery, like target identification, ligand fishing, assay development, lead selection and manufacturing quality control. However, there is increasing concern about its reproducibility in the light of the reproducibility crisis. Therefore an appropriate analytical instrument qualification (AIQ) is required for quality assurance of SPR instruments. AIQ is a prerequisite for analytical method validation and it is consisting of four parts, Design Qualification (DQ), Installation Qualification (IQ), Operational Qualification (OQ) and Performance Qualification (PQ). PQ regularly executed is supposed to continuously control the performance of the instrument under actual running conditions.In this work a performance qualification method was developed for the SPR instrument Biacore X100. This method is suitable for the routinely control of the instrument performance for antibody-antigen binding measurements. Control charts were designed to get a clearly representable and easy implementable tool to check the critical parameters. These control charts and a straightforward protocol now allow the design and application of an individual performance qualification procedure that can be used in the laboratory routine. They serve as reference for individual standard operation procedures (SOPs).

Effects of removing technical support staffs who are responsible for the external instruments on quality management of orthopedic surgery

Objective To explore the effects of multi-department cooperation and removing technical support staffs who are responsible for the external instruments on the quality management of the orthopedic surgery. Methods The old work pattern of operating room in our hospital was reformed from February 2015 to May 2016, with the help of information management platform and multi-disciplinary assistance and training. As a result, the technical support staffs who were responsible for the external instruments did not have to participate in the orthopedic surgery, and the surgical instruments could be managed by hospital staffs. The participation of the technical support staffs, the qualification of instruments cleaning, the precision of external instruments package, and the satisfaction of surgeons before and after the reformation were compared between two groups. Results The surgical categories had no difference before and after the reformation (P>0.05) . After the reformation, the participation of the technical support staffs significantly decreased from 80.00% to 2.97%; the qualification of instruments cleaning increased from 91.59% to 96.90%; the precision of the externall instruments package increased from 86.98% to 95.97%; and the satisfaction of surgeons increased from 55.10% to 93.14% (χ2=625.834, 65.930, 25.860, 195.671; P<0.01) . Conclusions The reformation of removing the technical support staffs who are responsible for the external instruments can be realized by the implementation of multi-department cooperation. It can highly improve the management quality and safety of the orthopedic surgery. Key words: Orthopedics operation; External instruments; Technical support staff; Multi-department cooperation

Gap Analysis for Chinese Drug Control Institutes to Achieve the Standards of World Health Organization Medicine Prequalification

The study aims to explore the challenges and the gaps faced by Chinese Drug Control Institutes in achieving the standards of World Health Organization (WHO) Medicine Prequalification. The study was undertaken with 6 Provincial Drug Control Institutes in China from November 2012 to November 2013. The study assessed key elements required to comply with WHO Good Practices for Pharmaceutical Quality Control Laboratories (GPPQCL). For GPPQCL, the study found gaps in quality management system, control of documentation, data-processing equipment, premises and equipment, contracts, reagents (water), reference substances and reference materials, calibration, verification of performance and qualification of equipment, instruments and other devices, analytical worksheet, evaluation of test results, personnel, and validation of analytical procedures. The study indicates that gaps are attributed to differences between the standards of Chinese Accreditation Standards and WHO-GPPQCL.

Evaluation of governmental oral health-care infrastructure in the state of Haryana.

Health system should be organized to meet the needs of entire population of the nation. Oral diseases are the most common of the chronic diseases, but there are few efficient dental care systems to cope with these problems. The present cross-sectional study was conducted among 135 dental care units of various primary health centers, community health centers, and general hospitals existing in the state to evaluate the government oral health-care infrastructure in Haryana. Data regarding provision of water and electricity supply, dental workforce and their qualification, number and type of instruments in the dental operatory unit, etc., were collected on a structured format. There is a shortfall in infrastructure and significant problem with the adequacy of working facilities. This can prove to be a big hurdle in the provision of adequate oral health care to people with greatest health-care needs. A great deal of effort is required to harmonize the oral health-care delivery system.

Status of governmental oral health care delivery system in Haryana, India.

Background:Health system should be organized to meet the needs of entire population of the nation. This means that the state has the direct responsibility for the health of its population and improving the quality of life through research, education, and provision of health services. The present study was conducted to evaluate the government oral health care delivery system in Haryana, India.Materials and Methods:The present cross-sectional study was conducted among 135 dental care units (DCUs) of various primary health centers (PHCs), community health centers (CHCs), and general hospitals (GHs) existing in the state by employing a cluster random sampling technique. Data regarding the provision of water and electricity supply, dental man power and their qualification, number and type of instruments in the dental operatory unit, etc., were collected on a structured format. Statistical analysis was done using number and percentages (SPSS package version 16).Results:Alternative source of electricity (generator) existed in only a few of health centers. About 93.4% (155) of the staff were graduates (BDS) and 6.6% (11) were postgraduates (MDS). Ultrasonic scaler was available at dental units of 83.1% (64) of PHCs, 73.1% (19) of CHCs, and 93.8% (30) of GHs. Patient drapes were provided in 48.1% (65) of the DCUs, doctor's aprons were provided in 74.1% (100) of the places.Conclusion:There is a shortfall in infrastructure and significant problem with the adequacy of working facilities. A great deal of effort is required to harmonize the oral health care delivery system.

The Impacts of Professional Ability to use ICT in Kharazmi University: a Case Study in Iran

Introduction: The purpose of this study was to investigate the factors affecting the use of ICT, especially the professional use of ICT during the teaching and learning process.Methods: This survey research was based on Kharazmi's teacher’s points of view on the use of ICT in the University. Of the 128 teachers selected from seven departments using convenience sampling method, 118 of them were made to answer the questions in the Likert-type questionnaire. The validity and reliability of the questionnaire were estimated in advance. Data were analyzed using SPSS software version 20, Pearson Chi-Square and ANOVA formula. Results: The results obtained showed that there was a relationship between the teacher's professional use of ICT and the qualification of related instruments during the teaching-learning process (p < 0.05, 0.01). However, different levels of satisfaction and approach to professional use of ICT in the departments were found to have no meaningful significance (p < 0.05, 0.01). The teachers' age and teaching backup were found to have no meaningful effects on the use of ICT (p < 0.05, 0.01).Conclusion: An approach is required for an improvement in teachers' professional use of ICT during teaching-learning process and preparation of qualified ICT facilities.

Early Identification of Unmanned Aircraft Pilots Using Measures of Personality and Aptitude

This study evaluated the extent to which personality measures (Self-Description Inventory+) could improve prediction of remotely piloted aircraft (RPA) training outcomes, beyond currently used cognitive, psychomotor, and aviation knowledge and experience predictors included in the U.S. Air Force (USAF) Pilot Candidate Selection Method 2.0. Participants were 170 USAF officers with RPA Initial Flight Screening (RFS) outcomes and 110 USAF officers with RPA Instrument Qualification (RIQ) outcomes. Both RFS and RIQ emphasize development of skills traditionally required for manned aircraft pilots, also considered essential for USAF RPA pilots. Results showed significant negative relationships between the Big Five personality trait of Openness and several RPA training outcomes, and significant incremental variance explained by Openness beyond other predictors. Additionally, RFS and RIQ training outcomes were generally predicted by measures traditionally used for selection into manned aircraft pilot training courses and careers. Together, these findings suggest that personality, specifically Openness scores, and scores on traditional pilot selection measures, can serve as useful indicators in the early identification of RPA pilot talent.

Qualification of Atomic Absorption Spectrometer in Prospective View of Pharmaceutical Analysis

AAS was qualified as per pharmacopoeia requirements. Copper, manganese, mercury and cadmium hallow cathode lamps were used for qualification purposes. Design qualification and installation qualification met the criteria of user requirements. Wavelength accuracy and reproducibility, resolution and baseline stability are in compliance with user requirements. Characteristics concentration or sensitivity, detection limit and characteristics mass were performed as a part of operational qualification which is 0.062 μg/mL, 0.00354 μg/mL, 1.41 pg respectively. Results of % RSD for precision study is 0.352 and 0.487 for flame and graphite furnace mode respectively fulfilled criteria of qualification. Performance qualification results of 20 consecutive days demonstrate the predetermined specification. Analytical instrument qualification and method validation relationship is also described by assay performed on haemodialysis concentrate. Good precision (2) greater than 0.9997 for potassium, magnesium and calcium linear curves, lower detection limits for all three ingredients and robust assay data as a part of validation studies conform the qualified AAS for its intended application.

Qualification of the Liquid Metal Ion Source Instruments for the NASA MMS Mission

The instruments for active spacecraft potential control to be launched with the NASA Magnetospheric Multiscale (MMS) mission in 2014 have recently been qualified, and the first two out of a total of eight flight models have completed their acceptance test campaign. At the heart of these instruments are liquid metal ion sources with indium, developed at Forschungsund Technologietransfer GmbH. Earlier versions have been flown in the Equator-S, Cluster, and Double Star missions. The redesign efforts to comply with the stringent requirements of the MMS mission are described in detail, as well as the qualification program for the emitters and the instruments. Starting with mechanical and thermal analyses and tests, continuing with performance and life testing, and finally by analysis of the overall performance in the mission application, it can be demonstrated that the new generation of ion emitters beats the performance of previous versions in all aspects. The description of verification efforts is completed by the results from tests at instrument level of the qualification model and the first flight models.

Analytical instrument qualification in capillary electrophoresis

Capillary electrophoresis (CE) is a well-established and frequently used technique in the pharmaceutical industry. Therefore an appropriate analytical instrument qualification (AIQ) is required for quality assurance. AIQ forms the basis of a quality management followed by analytical method validation, system suitability tests (SSTs) and quality control checks. Two parts of the AIQ, namely the operational qualification (OQ) and the performance qualification (PQ) are of particular interest in the daily routine of the laboratory. A new concept for OQ and PQ was developed to assure the correct function of a CE system. The significance of each parameter, possible test methods as well as acceptance criteria will be presented and discussed in detail. Especially temperature adjustment by the cooling system and the voltage supply must be tested for accurate and precise operation. The detector noise, wavelength accuracy and detector linearity have to be checked as well. Finally, the injection linearity, accuracy and precision need to be qualified. The proposed set of qualification procedures is easy to implement and was already tested on five CE instruments from three different manufacturers. A time- and cost-saving continuous PQ was derived, using results from method-specific SSTs and some additional experiments. This holistic concept continuously surveys the most relevant parameters, hence assuring the suitability of the used instruments and decreasing their downtimes.

A PROCEDURE FOR GENERATING IN-CABINET RESPONSE SPECTRA BASED ON STATE-SPACE MODEL IDENTIFICATION BY IMPACT TESTING

The in-cabinet response spectrum is used to define the input motion in the seismic qualification of instruments and devices mounted inside an electrical cabinet. This paper presents a procedure for generating the in-cabinet response spectrum for electrical equipment based on in-situ testing by an impact hammer. The proposed procedure includes an algorithm to build the relationship between the impact forces and the measured acceleration responses of cabinet structures by estimating the state-space model. This model is used to predict seismic responses to the equivalent earthquake forces. Three types of structural model are analyzed for numerical verification of the proposed method. A comparison of predicted and simulated response spectra shows good convergence, demonstrating the potential of the proposed method to predict the response spectra for real cabinet structures using vibration tests. The presented procedure eliminates the uncertainty associated with constructing an analytical model of the electrical cabinet, which has complex mass distribution and stiffness.