Equipment qualification and its application to conductivity measuring systems

It is only possible to obtain analytical results that are suitable for their intended purpose if the equipment used is capable of producing measurements of the required quality. To ensure that this requirement is met, analysts should define the performance criteria required from the instruments, ensure that only suitable instruments are selected for analytical measurements, and confirm that these instruments continue to meet these criteria for their entire operational life. This process should be conducted on a formal, documented basis, known as equipment qualification. In addition to describing the key elements of equipment qualification for all analytical instruments, this paper gives specific guidance on its application to conductivity systems that has never previously appeared in the literature. The benefits of performing equipment qualification are highlighted and guidance is given on the selection of control standards and why the equipment vendor performing stages of equipment qualification can be of benefit to the user. The relationship between equipment qualification and method validation is discussed, including how these activities play a major role in determining the quality control measures that should be applied to routine analysis.     

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.     

Automation and validation of HPLC-systems

Summary The automation of chromatographic systems is of increasing interest to industry and research laboratories in routine applications. Besides potentially saving time or making better use of available instrumentation, automation also improves the quality of results by producing more precise and more reproducible HPLC data. The need for the validation of methods and qualification of instruments is increasingly recognised in order to ensure compliance with legal requirements (e.g. in the pharmaceutical industry) and to ensure the reliability of analytical results. Possibilities and requirements for automated HPLC systems are elaborated. Emphasis is placed on defining the goals of validation and on discussing different aspects of the validation of LC methods, system suitability tests, ruggedness of methods and the transfer of LC methods from laboratory to laboratory. Adequate strategies of HPLC method development provide very useful information on the validation and ruggedness of LC methods.     

Qualification and validation of software and computer systems in laboratories

 When software and computer systems are purchased from vendors, the user is still responsible for the overall validation. Because the development validation can only be done by the developers, the user can delegate this part to the vendor. The user's firm should have a vendor qualification program in place to check for this. The type of qualification depends very much on the type and complexity of software and can go from documented evidence of ISO 9001 or equivalent certification for off-the-shelf products to direct audit for software that has been developed on a contract basis. Using a variety of practical examples, the article will help to find the optimal qualification procedure. Received: 8 August 1997 · Accepted: 12 September 1997     

Instrumental validation in capillary electrophoresis and checkpoints for method validation

Capillary electrophoresis (CE) is increasingly being used in regulated and testing environments which demand validation. The design, development and production of CE instrumentation should be governed by qualifications which ensure the quality of the finished product. The vendor should therefore provide guidelines and procedures which assist the user in ensuring the adequate operation of the instrumentation and especially in designing installation qualification (IQ) and operational qualification/performance verification (OQ/PV) procedures. OQ/PV should test those functions of an instrument which directly affect the CE analysis, i.e. voltage, temperature, injection precision and detector function. In validation of CE methods care should be taken that those aspects which directly affect the precision of peak parameters are appreciated. The relationship between CE instrumentation, chemistry and validation parameters is discussed and guidelines are presented for definition of a CE method for submission to regulatory authorities.     

Method validation and qualification of instruments for atomic spectrometry

This work describes the analytical procedures for atomic absorption and inductively coupled plasma (ICP) techniques that have to be used in order to obtain a license to sell drugs in the USA. The qualification of atomic absorption spectrometers and ICP instruments is described. The method validation characteristics, e.g., accuracy, precision, linearity, range, detection limits, and quantification are discussed. The time involved and the quality of documentation are pointed out. The consequences for laboratory personnel and operating costs are also discussed.     

色谱类分析仪器性能确认用标准物质的筛选

分析仪器验证是制药、食品、环境等多个行业实验室质量管理的重点,为解决我国色谱类分析仪器验证评价体系中缺乏统一标准物质的问题,提出了筛选性能确认行业推荐用标准物质的原则。通过分析不同行业色谱类分析仪器标准物质使用情况和国家标准及有证标准物质的发布现状,以筛选原则为指导,筛选出93种高效液相色谱性能确认用标准物质。为保证分析仪器的稳定性和可靠性提供了标准依据。     

Ion chromatography characterization of polysaccharides in ancient wall paintings

Specific programming of automated HPLC systems allows total on-line qualification, validation and stability monitoring using the concept of deferred standards. Setting up such a process for routine analyses in an automated HPLC system requires specific autosampler programming as well as specific monitoring software. With an autosampler, a double injection procedure is programmed, the first introducing the sample, and the second, a few minutes deferred, the deferred control standard. Two additional compounds are therefore added to the sample before and during the chromatographic process: the intemal standard for sample quantification and the deferred standard for system control. Specific methodologies are described of how to obtain classical quantitative analysis information as well as system qualification validation stability information. Experiments were performed to develop specified methodologies to monitor the quality of quantitative analysis during the life of the column by using the deferred standard concept to probe the effects of column ageing on separation characteristics.     

Specificity rule discovery in HIV-1 protease cleavage site analysis

Several machine learning algorithms have recently been applied to modeling the specificity of HIV-1 protease. The problem is challenging because of the three issues as follows: (1) datasets with high dimensionality and small number of samples could misguide classification modeling and its interpretation; (2) symbolic interpretation is desirable because it provides us insight to the specificity in the form of human-understandable rules, and thus helps us to design effective HIV inhibitors; (3) the interpretation should take into account complexity or dependency between positions in sequences. Therefore, it is necessary to investigate multivariate and feature-selective methods to model the specificity and to extract rules from the model. We have tested extensively various machine learning methods, and we have found that the combination of neural networks and decompositional approach can generate a set of effective rules. By validation to experimental results for the HIV-1 protease, the specificity rules outperform the ones generated by frequency-based, univariate or black-box methods.     

Qualification and validation of software and computer systems in laboratories

 Installation and operational qualification are important steps in the overall validation and qualification process for software and computer systems. This article guides users of such systems step by step through the installation and operational qualification procedures. It provides guidelines on what should be tested and documented during installation prior to routine use. The author also presents procedures for the qualification of software using chromatographic data systems and a network server for central archiving as examples. Received: 31 October 1997 · Accepted: 25 November 1997     

Practical and theoretical implications of target values in clinical chemistry: a QC approach

The automation of test validation procedures in a routine clinical laboratory by integrating artificial intelligence with the lab information system (LIS) is the focus of this study. Test validation consists of three layers: (1) acceptance of patient results based on technical criteria (technical validation), (2) acceptance of patient results based on internal quality control (QC) results (QC validation) and (3) medical validation of the patient protocol. The emphasis here is put on QC validation. General concepts regarding the setting of performance limits for internal QC results are briefly reviewed. As a practical example, we describe how the different layers of test validation were integrated with Molis, a LIS (Sysmex, Barchon, Belgium) used in a routine clinical biochemistry lab. PGP5 software (PGP, Brussels, Belgium) is used for technical validation and is installed on a Linx work-cell (Thermo Clinical Labsystems, Vantaa, Finland). The latter integrates four different Vitros instruments (OCD, Beerse, Belgium). QC validation and medical validation are performed with QC-Today (IL, Zaventem, Belgium) and VALAB (Erim, Toulouse, France), respectively. Both programs are bi-directionally coupled with the LIS. After 2 years of experience with this integrated system, it is clear that automation of validation rules and procedures has enhanced efficiency and overall quality of patient results.Presented at the Ninth Conference on Quality in the Spotlight, 18–19 March 2004, Antwerp, Belgium.     

Selecting parameters and limits for equipment operational qualification

While operational qualification (OQ) is a well-established term within equipment qualification, users of equipment often become unsure when it comes to implementation. The biggest problem is how to select procedures and acceptance criteria. Should these be the vendor's specifications or should the users define their own limits, and, if so, how? Should all instruments of the same type have the same values or should these be optimized for each individual instrument? This article will provide an overall strategy and specific examples for HPLC on how to select procedures and acceptance limits that are based on efficient use of resources, on practicality and on the intended use of the equipment.     

Thermal Analysis as Part of the Quality System within Industrial Laboratories

The use of thermal analysis as part of a quality system in industry can be effective only if the techniques are made to conform to high standards of quality assurance. Achieving these high standards is not problem free and there remain many issues which require the attention of thermal analysts in industry and academe. Fundamental aspects which have been considered include limitations due to instrument design, problems in computerised control and analysis. A key aim is towards validation of data at international level. This revised version was published online in August 2006 with corrections to the Cover Date.     

物理化学设计实验教学的实践与体会

介绍了南京大学物理化学实验课程中设计实验的开设情况。在设计实验教学过程中,通过选取主导仪器、递交初步计划、陈述实验方案和完成设计实验4个环节的训练,有效促进了学生综合素质和创新能力的培养,取得了良好的教学效果。     

Accrediation of laboratories: the modular system of assessment

 An accreditation body has to guarantee that the assessment of laboratories follows appropriate and uniform rules. This procedure must be independent of the assessor. The "DACH Deutsche Akkreditierungsstelle Chemie GmbH" has developed such a procedure using the proposal first presented by Eggimann and Morkowski. A procedure is described, where by the quality requirements of the standard EN 45001 are allocated to four modules. The modules and corresponding questionnaire are presented. Received: 30 September 1995 Accepted: 25 October 1995     

Practical aspects concerning validation and quality control for forensic and clinical bioanalytical quantitative methods

Reporting reliable analytical data is the backbone of forensic and clinical bioanalytical research and applications. Therefore, international agreement concerning validation and quality control requirements is needed. Several international guidelines provide a standard for fundamental validation parameters such as selectivity, matrix effects, method limits, calibration, accuracy, precision and stability. However, it is not always easy for the analyst to ‘translate’ these guidelines into practice. International guidelines remain nonbinding protocols that need to be updated according to the type of application and the analyst’s method requirements and depends on the evolution of analytical techniques. In this publication, suggestions for experimental set-up, statistical approaches and straightforward acceptance criteria for validation of forensic bioanalytical applications are suggested. Furthermore, permanent quality control, to ensure state-of-the-art quantitative analytical performances, as well as measurement uncertainty influencing interpretation is discussed.     

Evaluation of matrix effect and chromatography efficiency: new parameters for validation of method development

From the viewpoint of regulatory guidelines, validation of LC-UV and LC-MS based methods have the same requirements. Matrix effects are not considered for most method validations if they do not influence reproducibility or assay linearity. Since matrix effects can strongly suppress ionizaton efficiency and therefore reduce sensitivity, they must be evaluated (and discussed in the context of method development)--prior to method qualification. The severity of matrix effects is directly dependent upon chromatographic performance. We suggest that evaluation of matrix effects and LC efficiency is essential information for method assessment, optimization and transfer to other mass spectrometers, and should be a mandatory part of routine LC/MS method validation.     

Quality assurance and instrumentation

 The quality process for commercial analytical equipment starts with the selection of the vendor. It is recommended that vendors be selected who are recognized as having quality processes in place for instrument design, development, manufacturing, testing, service, and support, for example, ISO 9001 registration. When the instrument arrives in the laboratory, the installation process should follow well-documented procedures. This includes a visual inspection that the instrument is not damaged and checking that the instrument, documentation and accessories such as cables and tubings are complete. Before the instrument is used it should be verified that it meets functional and performance specification. During operation the instruments should be periodically inspected and tested, verified to meet performance, and calibrated. The instrument should be labeled with the calibration status, indicating the dates of the last successful and the next performance verification and calibration. Defective instruments should be removed from the testing area or should at least be labeled as being "out of order." Received 23 August 1995 Accepted 6 September 1995